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Hematopoietic Cell Transplantation for Non-Hodgkin Lymphomas

Policy Number: MP-387

Latest Review Date: February 2021

Category: Therapy                                                                 

Policy Grade: B

POLICY:

Effective for dates of services on or after August 23, 2011:

For patients with non-Hodgkin lymphoma (NHL) B-cell subtypes considered aggressive (except mantle cell lymphoma), either allogeneic hematopoietic stem cell transplantation (HCT) using a myeloablative conditioning regimen or autologous HCT may be considered medically necessary:

  • As salvage therapy for patients who do not achieve a complete remission (CR) after first-line treatment (induction) with a full course of standard-dose chemotherapy;

  • To achieve or consolidate a CR for those in a chemosensitive first or subsequent relapse; or

  • To consolidate a first CR in patients with diffuse large B-cell lymphoma, with an age-adjusted International Prognostic Index score that predicts a high- or high-intermediate risk of relapse.

For patients with mantle cell lymphoma:

  • Autologous HCT may be considered medically necessary to consolidate a first remission.

  • Allogeneic HCT, myeloablative or reduced-intensity conditioning, may be considered medically necessary as salvage therapy.

  • Autologous HCT is considered investigational as salvage therapy.

  • Allogeneic HCT is considered investigational to consolidate a first remission.

For patients with NHL B-cell subtypes considered indolent, either allogeneic HCT using a myeloablative conditioning regimen or autologous HCT may be considered medically necessary:

  • As salvage therapy for patients who do not achieve CR after first-line treatment (induction) with a full course of standard-dose chemotherapy; or

  • To achieve or consolidate CR for those in a first or subsequent chemosensitive relapse, whether or not their lymphoma has undergone transformation* to a higher grade.

*Transformation describes a lymphoma whose histologic pattern has evolved to a higher-grade lymphoma. Transformed lymphomas typically evolve from a nodular pattern to a diffuse pattern.

Reduced-intensity conditioning (RIC) allogeneic HCT may be considered medically necessary as a treatment of NHL in patients who meet criteria for an allogeneic HCT but who do not qualify for a myeloablative allogeneic HCT.

Either autologous HCT or allogeneic HCT are considered investigational:

  • As initial therapy (i.e., without a full course of standard-dose induction chemotherapy) for any NHL;

  • To consolidate a first CR for patients with diffuse large B-cell lymphoma and an International Prognostic Index score that predicts a low- or low-intermediate risk of relapse;

  • To consolidate a first CR for those with indolent NHL B-cell subtypes.

Tandem transplants is considered investigational to treat patients with any stage, grade, or subtype of NHL.

For patients with mature *T-cell or NK-cell (peripheral T-cell) neoplasms:

  • Autologous HCT may be considered medically necessary to consolidate a first complete remission in high-risk peripheral T-cell lymphoma.

  • Autologous or allogeneic HCT (myeloablative or reduced-intensity conditioning) may be considered medically necessary as salvage therapy.

  • Allogeneic HCT is considered investigational to consolidate a first remission.

* The T-cell and NK-cell neoplasm are a clinically heterogeneous group of rare disorders, most of which have an aggressive clinical course and poor prognosis. The exception would include the following subtypes which typically have a relatively indolent and protracted course: T-cell large granulocyte leukemia (T-LGL), chronic lymphoproliferative disorder of NK cells, early stage mycosis fungoides, primary cutaneous ALCL, and ALK+ ALCL.

For patients with Waldenström Macroglobulinemia:

  • Autologous hematopoietic cell transplantation may be considered medically necessary as salvage therapy of chemosensitive Waldenström Macroglobulinemia.

  • Allogeneic hematopoietic cell transplantation is considered investigational to treat Waldenström Macroglobulinemia.

POLICY GUIDELINES:

Note:  The term salvage therapy describes therapy given to patients who have either:

  1. Failed to achieve complete remission after initial treatment for newly diagnosed lymphoma, or

  2. Relapsed after an initial complete remission.

A chemosensitive relapse is defined as relapsed non-Hodgkin lymphoma (NHL) that does not progress during or immediately after standard-dose induction chemotherapy (i.e., achieves stable disease or a partial response).

Note: Reduced-intensity conditioning (RIC) would be considered an option in patients who meet criteria for an allogeneic hematopoietic stem-cell transplant (HCT) but whose age (typically older than 55 years) or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, and prior intensive chemotherapy) preclude use of a standard conditioning regimen.

In patients who qualify for a myeloablative allogeneic hematopoietic HCT based on overall health and disease status, allogeneic HCT using either myeloablative or RIC may be considered. However, a myeloablative conditioning regimen with allogeneic HCT may benefit younger patients with good performance status and minimal comorbidities more than allogeneic HCT with RIC.

Tandem transplants usually are defined as the planned administration of two successive cycles of high-dose myeloablative chemotherapy, each followed by infusion of autologous hematopoietic stem cells, whether or not there is evidence of persistent disease following the first treatment cycle. Sometimes, the second cycle may use non-myeloablative immunosuppressive conditioning followed by infusion of allogeneic stem cells.

DESCRIPTION OF PROCEDURE OR SERVICE:

Non-Hodgkin Lymphoma

A heterogeneous group of lymphoproliferative malignancies, NHL usually originates in lymphoid tissue. Historically, uniform treatment of patients with NHL was hampered by the lack of a uniform classification system. In 1982, the Working Formulation was developed to unify different classification systems into one. The Working Formulation divided NHL into low-, intermediate-, and high-grade, with subgroups based on histologic cell type. Because our understanding of NHL has improved, the diagnosis has become more sophisticated and includes the incorporation of new immunophenotyping and genetic techniques. As a result, the Working Formulation has become outdated.

European and American pathologists proposed a new classification, the Revised European-American Lymphoma (REAL) Classification and an updated version of the REAL system, the new World Health Organization classification. The WHO/REAL classification recognized three major categories of lymphoid malignancies based on morphology and cell lineage: B-cell neoplasms, T-cell/natural killer cell neoplasms, and Hodgkin lymphoma.

Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT) refers to a procedure by which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of cytotoxic drugs, with or without whole-body radiotherapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HCT) or a donor (allogeneic HCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates. Although umbilical cord blood is an allogeneic source, the stem cells in it are antigenically “naive” and thus are associated with a lower incidence of rejection or graft-versus-host disease (GVHD).

A heterogeneous group of lymphoproliferative malignancies, NHL usually originates in lymphoid tissue. Historically, uniform treatment of patients with NHL was hampered by the lack of a uniform classification system.  In 1982, the Working Formulation (WF) was developed to unify different classification systems into one.  The WF divided NHL into low-, intermediate-, and high-grade, with subgroups based on histologic cell type.  Since our understanding of NHL has improved, the diagnosis has become more sophisticated and includes the incorporation of new immunophenotyping and genetic techniques.  As a result, the WF has become outdated.

European and American pathologists proposed a new classification, the Revised European American Lymphoma (REAL) Classification, and an updated version of the REAL system, the new World Health Organization (WHO) classification. The WHO/REAL classification recognizes three major categories of lymphoid malignancies based on morphology and cell lineage: B-cell neoplasms, T-cell/natural killer (NK)-cell neoplasms, and Hodgkin lymphoma.

The most recent lymphoma classification is the 2008 WHO classification (see Table 1).

Table 1. Updated WHO Classification (2016)

Classification of Neoplasms

Mature B-cell neoplasms

Chronic lymphocytic leukemia/small lymphocytic lymphoma

Monoclonal B-cell lymphocytosisa

B-cell prolymphocytic leukemia

Splenic marginal zone lymphoma

Hairy cell leukemia

Splenic lymphoma/leukemia, unclassifiable

  • Splenic diffuse red pulp small B-cell lymphoma

  • Hairy cell leukemia-variant

Lymphoplasmacytic lymphoma

  • Waldenström macroglobulinemia

Monoclonal gammopathy of undetermined significance, IgMa

Heavy chain diseases

  • Alpha heavy chain disease

  • Gamma heavy chain disease

  • Mu heavy chain disease

Monoclonal gammopathy of undetermined significance, IgG/IgAa

Plasma cell myeloma

Solitary plasmacytoma of bone

Extraosseous plasmacytoma

Monoclonal immunoglobulin deposition diseasesa

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)

Nodal marginal zone lymphoma (MZL)

  • Pediatric nodal MZL

Follicular lymphoma

  • In situ follicular neoplasiaa

  • Duodenal-type follicular lymphomaa

Pediatric type follicular lymphomaa

  • Large B-cell lymphoma with IRF4 rearrangementa

Primary cutaneous follicle center lymphoma

Mantle cell lymphoma

  • In situ mantel cell neoplasiaa

Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)

  • Germinal center B-cell typea

  • Activated B-cell typea

T-cell/histiocyte-rich large B-cell lymphoma

DLBCL associated with chronic inflammation

Lymphomatoid granulomatosis

Primary mediastinal (thymic) large B-cell lymphoma

Intravascular large B-cell lymphoma

Primary cutaneous DLBCL, leg type

ALK [anaplastic lymphoma kinase]-positive large B-cell lymphoma

Plasmablastic lymphoma

Primary effusion lymphoma

HHV8 DLBCL NOSa

Burkitt lymphoma

Burkitt-like lymphoma with 11q aberrationa

High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6rearrangementsa

High-grade B-cell lymphoma, NOSa

B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma

Mature T-cell and NK-cell neoplasms

T-cell prolymphocytic leukemia

T-cell large granular lymphocytic leukemia

Chronic lymphoproliferative disorder of NK cells

Aggressive NK-cell leukemia

Systemic Epstein-Barr virus-positive T-cell lymphoproliferative of childhooda

Hydroa vacciniforme-like lymphoproliferative disordera

Adult T-cell leukemia/ lymphoma

Extranodal NK/T-cell lymphoma, nasal type

Enteropathy-associated T-cell lymphoma

Monomorphic epitheliotropic intestinal T-cell lymphomaa

Indolent T-cell lymphoproliferative disorder of the GI tracta

Hepatosplenic T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma

Mycosis fungoides

Sézary syndrome

Primary cutaneous CD30-positive T-cell lymphoproliferative disorder

  • Lymphomatoid papulosis

  • Primary cutaneous anaplastic large-cell lymphoma

Primary cutaneous gamma-delta T-cell lymphoma

Primary cutaneous aggressive epidermotropic CD8-positive cytotoxic T-cell lymphomaa

Primary cutaneous acral CD8+ T-cell lymphomaa

Primary cutaneous small/medium CD4-positive T-cell lymphoproliferative disordera

Peripheral T-cell lymphoma, NOS

Angioimmunoblastic T-cell lymphoma

Follicular T-cell lymphomaa

Nodal peripheral T-cell lymphoma with TFH phenotypea

Anaplastic large-cell lymphoma (ALCL), ALK-positive

Anaplastic large-cell lymphoma (ALCL), ALK-negativea

Breast implant-associated anaplastic large-cell lymphomaa

Histiocytic Sarcoma

ALK: anaplastic lymphoma kinase; GI: gastrointestinal; Ig: immunoglobulin; NK: natural killer.

a Changes from 2008 WHO classification. Provisional entities are listed in italics.

In the United States, B-cell lymphomas represent 80% to 85% of cases of NHL, and T-cell lymphomas represent 15% to 20%. NK lymphomas are relatively rare.

The International Lymphoma Classification Project identified the most common NHL subtypes as follows: diffuse large B-cell lymphoma (DLBCL) 31%, follicular lymphoma 22%, small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL) 6%, mantle cell lymphoma (MCL) 6%, peripheral T-cell lymphoma (PTCL) 6%, and marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma 5%. All other subtypes each represent fewer than 2% of cases of NHL.

Treatment for NHL

Hematopoietic Cell Transplantation

Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an issue in autologous HCT. However, immunologic compatibility between donor and patient is critical for achieving a good outcome with allogenic HCT. Compatibility is established by typing of human leukocyte antigens (HLAs) using cellular, serologic, or molecular techniques. HLA refers to the tissue type expressed at the HLA-A, -B, and -DR loci on each arm of chromosome 6. Depending on the disease being treated, an acceptable donor will match the patient at all or most of the HLA loci (with the exception of umbilical cord blood).

Waldenström Macroglobulinemia

Waldenström Macroglobulinemia (WM) is a clonal disorder of B-lymphocytes that accounts for 1% to 2% of hematologic malignancies, with an estimated 1500 new cases annually in the United States. Symptoms include weakness, headaches, stroke-like symptoms (confusion, loss of coordination), vision problems, excessive bleeding, unexplained weight loss, and frequent infections. The median age of WM patients does 63 to 68 years, with men comprise 55% to 70% of cases. Median survival of WM ranges from five to 10 years, with age, hemoglobin concentration, serum albumin level, and ß2-microglobulin level as predictors of outcome.

The Revised European American Lymphoma and World Health Organization classification and a consensus group formed at the Second International Workshop on Waldenström’ s Macroglobulinemia recognize WM primarily as a lymphoplasmacytic lymphoma with an associated immunoglobulin M (IgM) monoclonal gammopathy. The definition also requires the presence of a characteristic pattern of bone marrow infiltration with small lymphocytes demonstrating plasmacytic differentiation with variable cell surface antigen expression. The Second International Workshop indicated no minimum serum concentration of IgM is necessary for a diagnosis of WM.

Treatment

The goal of therapy for patients with WM is to achieve symptomatic relief and reduce organ damage without compromising quality of life. Treatment of WM is indicated only in symptomatic patients and should not be initiated solely based on serum IgM concentration. Clinical and laboratory findings that indicate the need for therapy of diagnosed WM include a hemoglobin concentration less than 10 g/dL; platelet count less than 100,000/ųL; significant adenopathy or organomegaly; symptomatic Ig-related hyperviscosity (>50 g/L); severe neuropathy; amyloidosis; cryoglobulinemia; cold-agglutinin disease; or evidence of disease transformation.

Primary chemotherapeutic options in patients that may undergo autologous hematopoietic cell transplantation (HCT) often combine rituximab with other agents (e.g., dexamethasone, cyclophosphamide, bortezomib, bendamustine), but other agents may also be used including purine analogues (cladribine, fludarabine). Plasma exchange is indicated for acute treatment of symptomatic hyperviscosity.

Conventional Preparative Conditioning for HCT

The conventional practice of allogeneic HCT involves administration of cytotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation; this is performed at doses sufficient to destroy endogenous hematopoietic capability in the recipient. The beneficial treatment effect of this procedure is due to a combination of initial eradication of malignant cells and subsequent graft-versus-malignancy effect that is mediated by non-self-immunologic effector cells that develop after engraftment of allogeneic stem cells within the patient’s bone marrow space. While the slower graft-versus-malignancy effect is considered the potentially curative component, it may be overwhelmed by extant disease without the use of pretransplant conditioning. However, intense conditioning regimens are limited to patients who are medically fit to tolerate substantial adverse events that include preengraftment opportunistic infections secondary to loss of endogenous bone marrow function and organ damage and failure caused by the cytotoxic drugs. Furthermore, in any allogeneic HCT, immunosuppressant drugs are required to minimize graft rejection and graft-versus-host disease, which also increase susceptibility to opportunistic infections. The immune reactivity between donor T cells and malignant cells is responsible for the graft-versus-malignancy effect; it also leads to acute and chronic graft-versus-host disease.

The success of autologous HCT is predicated on the ability of cytotoxic chemotherapy (with or without radiation) to eradicate cancerous cells from the blood and bone marrow. This permits subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic stem cells obtained from the patient before undergoing bone marrow ablation. Therefore, autologous HCT is typically performed when the patient’s disease is in complete remission. Patients who undergo autologous HCT are susceptible to chemotherapy-related toxicities and opportunistic infections before engraftment, but not graft-versus-host disease.

Reduced-Intensity Conditioning for Allogeneic HCT

Reduced-intensity conditioning (RIC) refers to the pretransplant use of lower doses or less intense regimens of cytotoxic drugs or radiation than are used in conventional full-dose myeloablative conditioning treatments. The goal of RIC is 2-fold: to reduce disease burden, and to minimize treatment-related morbidity and nonrelapse mortality in the period during which the beneficial graft-versus-malignancy effect of allogeneic transplantation develops. Although the definition of RIC remains arbitrary, with numerous versions employed, all seek to balance the competing effects of nonrelapse mortality and relapse due to residual disease. RIC regimens can be viewed as a continuum—from nearly totally myeloablative to minimally myeloablative with lymphoablation—because it tailors its intensity to specific diseases and patient condition. Patients who undergo RIC with allogeneic HCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full-donor chimerism, which may be supplemented with donor lymphocyte infusions to eradicate residual malignant cells. For the purposes of this evidence review, reduced-intensity conditioning will refer to all conditioning regimens intended to be nonmyeloablative, as opposed to fully myeloablative (traditional) regimens.

KEY POINTS:

The most recent literature update was performed through November 19, 2020.

Summary of Evidence

For individuals who have indolent B-cell non-Hodgkin lymphomas who receive autologous HCT as first-line therapy, the evidence includes randomized trials and systematic reviews. Relevant outcomes are overall survival, disease-specific survival, change in disease status, morbid events, and treatment-related mortality and morbidity. Randomized trials have not shown a survival advantage with HCT as first-line therapy for indolent B-cell lymphomas; however, randomized studies have shown a survival benefit for relapsed disease. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have aggressive B-cell non-Hodgkin lymphomas who receive autologous HCT as consolidation therapy after first complete remission, the evidence includes randomized trials and systematic reviews. Relevant outcomes are overall survival, disease-specific survival, change in disease status, morbid events, and treatment-related mortality and morbidity. While the data from the randomized trials offer conflicting results, some of the data has revealed an overall survival benefit in patients with aggressive B-cell lymphomas (at high or high-intermediate risk of relapse) who receive HCT to consolidate a first complete remission. Randomized studies of HCT for relapsed aggressive B-cell lymphomas have shown an overall survival benefit with the previously described approach. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have non-Hodgkin lymphomas who receive tandem autologous and allogeneic HCT, the evidence includes several nonrandomized trials. Relevant outcomes are overall survival, disease-specific survival, change in disease status, morbid events, and treatment-related mortality and morbidity. No randomized studies have been conducted on the use of tandem HCT for the treatment of non-Hodgkin lymphoma, and the published evidence comprises a limited number of patients. Presently, conclusions on the use of tandem transplants cannot be made about autologous and allogeneic HCT. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have mantle cell lymphoma who receive autologous, allogeneic, or tandem HCT, the evidence includes case series. Relevant outcomes are overall survival, disease-specific survival, change in disease status, morbid events, and treatment-related mortality and morbidity. Due in part to the rarity of this disease, randomized trials on the use of HCT in mantle cell lymphoma have not been conducted. Case series have shown long-term disease control of this aggressive lymphoma with autologous HCT (with rituximab) to consolidate a first remission; however, the use of autologous HCT in the relapsed setting has not shown improved outcomes. Allogeneic HCT has shown prolonged disease control in the relapsed or refractory setting. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have peripheral T-cell lymphoma (PTCL) who receive autologous or allogeneic HCT, the evidence includes prospective trials and case reports. Relevant outcomes are overall survival, disease-specific survival, change in disease status, morbid events, and treatment-related mortality and morbidity. The role of HCT in PTCL is not well defined. Few studies have been conducted, and most were performed retrospectively, with a limited number of patients; further the patient populations were heterogeneous and included good- and poor-risk patients in the same study. Patient population and characteristics of the studies can be explained partially by the rarity and heterogeneity of the particular group of lymphomas in which the study addresses. Additionally, studies of this nature are often the mix of three types of patients: A patient with PTCL, not otherwise specified, which has a poorer prognosis; anaplastic lymphoma kinase (ALK) positive and anaplastic large-cell lymphomas (ALCL), which has a better prognosis; and ALK-negative ALCL, which has a worse prognosis than ALK-positive ALCL (but better than patients with PTCL not otherwise specified). There have been no randomized studies comparing chemotherapy regimens solely in patients with PTCL (i.e., some randomized studies have included PTCL with aggressive B-cell lymphomas). For front-line therapy, results from recent phase 2 studies with autologous HCT as consolidation offers the best survival outcomes for patients with high-risk features; randomized trials to confirm this have not been performed. No relevant data for the use of allogeneic HCT in the first-line setting are available. Patients with relapsed or refractory PTCL are generally considered incurable with chemotherapy alone. In the salvage setting, data have shown that the use of HCT may improve survival outcomes similar to the results seen in corresponding aggressive B-cell lymphomas in the same treatment setting. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have WM who receive HCT, the evidence includes case series. Relevant outcomes are overall survival, change in disease status, quality of life, and treatment-related mortality and morbidity. Several retrospective series have evaluated HCT for WM. Analyses of registry data have found 5-year overall survival rates of 52% after allogeneic HCT and 68.5% after autologous HCT. The total number of patients studied is small and there is a lack of published controlled studies. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Positon Statement

National Comprehensive Cancer Network

Current National Comprehensive Cancer Network guidelines on B-cell lymphomas (v.4.2020) include the following recommendations:

  • For follicular lymphoma, marginal zone lymphomas, and mantle cell lymphoma, recommend allogeneic HCT as second-line consolidation therapy.

  • For DLBCL, “[a]llogeneic HCT should be considered in selected patients with mobilization failures and persistent bone marrow involvement or lack of adequate response to second-line therapy, though patients should be in CR or near CR at the time of transplant.”

  • For Burkitt lymphoma, allogeneic HCT is an option for selected patients to achieve a complete or partial response to second-line therapy.

National Comprehensive Cancer Network guidelines on T-cell lymphomas (v.1.2021) include the following recommendations:

“Second-line systematic therapy followed by consolidation with HDT [high-dose therapy]/ASCR [autologous stem cell rescue] or allogeneic HCT for those with a CR [complete response] or PR [partial response] is recommended for patients who are candidates for transplant.”

“In patients with acute or lymphoma subtypes who achieve a response to second-therapy, allogeneic HSCT should be considered if a donor is available.”

“In patients [with T-PLL] who achieve a CR or PR following initial therapy, consolidation with allogeneic HCT should be considered. Autologous HCT may be considered, if a donor is not available and if the patient is not physically fit enough to undergo allogeneic HCT.”

National Comprehensive Cancer Network guidelines on Waldenström macroglobulinemia (WM) and lymphoplasmacytic lymphoma (v.1.2021) include the following recommendations:

National Comprehensive Cancer Network guidelines on Waldenström macroglobulinemia (WM) and lymphoplasmacytic lymphoma (v.1.2021) indicate that, for patients with previously treated WM, stem cell transplantation may be appropriate in selected cases with either: high-dose therapy with autologous stem cell rescue or allogeneic cell transplant (myeloablative or nonmyeloablative). The Network noted that allogeneic cell transplantation “should ideally be undertaken in the context of a clinical trial.” For potential autologous cell transplantation candidates, the guidelines also provide suggested treatment regimens considered non-stem-cell toxic.

Mayo Clinic Cancer Center

In 2017, the Mayo Clinic Cancer Center updated its guidelines on the diagnosis and management of WM. The guidelines noted that patients who are potentially eligible for autologous hematopoietic cell transplantation (HCT; <70 years of age and with chemosensitive disease), should consider harvesting stem cells during first remission after a low tumor burden has been achieved. The guidelines recommended: “Autologous HCT should be considered for first or second relapse in transplant-eligible patients with chemosensitive disease, especially if the first remission duration is short (<2 years). Patients with refractory WM should not be offered [autologous HCT] (level 3, grade B).”

Eighth International Workshop on Waldenström’s Macroglobulinemia

In 2016, consensus recommendations from the Eighth International Workshop on Waldenström Macroglobulinemia were published. The panel concluded that autologous hematopoietic cell transplantation (HCT) is a treatment option for high-risk WM patients who are eligible for transplant. They further stated that autologous HCT should be offered at early relapses and is not as beneficial once patients have been exposed to more than three lines of therapy or in those with chemotherapy refractory disease. Regarding allogeneic HCT, they stated that this treatment, “when appropriate, should preferably be considered in the context of clinical trials.”

Myeloma Foundation of Australian

In 2017, the Myeloma Foundation of Australia published practice guidelines on the treatment of patients with WM. The guidelines provided the following treatment recommendation for HCT: “Younger patients with good physical fitness should be considered for autologous and allogeneic stem cell transplantation at first or second relapse and should avoid stem cell-toxic therapies such as fludarabine (Level III, grade C).”

U.S Preventive Services Task Force Recommendations

Not Applicable.

KEY WORDS:

High-Dose Chemotherapy, Non-Hodgkin’s Lymphoma, Lymphoma, Stem-Cell Transplant, Diffuse Large B-Cell Lymphoma, DLBCL, Mantle Cell Lymphoma, MCL, Peripheral T-Cell Lymphoma, PTCL, Follicular Lymphoma, Hematopoietic Cell Transplantation, HCT, anaplastic large-cell lymphoma, and ALCL, Histiocytic Sarcoma, HS, Waldenström Macroglobulinemia

APPROVED BY GOVERNING BODIES:

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation title 21, parts 1270 and 1271. Hematopoietic stem cells are included in these regulations.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.

CURRENT CODING:

CPT Codes:

38204

Management of recipient hematopoietic cell donor search and cell acquisition 

38205

Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection, allogeneic 

38206

Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection, autologous 

38208

Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, without washing; per donor

38209

; thawing of previously frozen harvest with washing; per donor

38210

; specific cell depletion with harvest, T cell depletion

38211

; tumor cell depletion

38212

; red blood cell removal 

38213

; platelet depletion

38214

; plasma (volume) depletion

38215

; cell concentration in plasma, mononuclear, or buffy coat layer

38220

Diagnostic bone marrow; aspiration(s)

38221

Diagnostic bone marrow; biopsy (ies),

38222

Diagnostic bone marrow; biopsy (ies) and aspiration(s) (Effective 01/01/2018)

38230

Bone marrow harvesting for transplantation; allogeneic

38232

; autologous (Effective for dates of service on or after January 1, 2012)

38240

Bone marrow or blood-derived peripheral stem-cell transplantation; allogeneic 

38241

Bone marrow or blood-derived peripheral stem-cell transplantation; autologous                          

 

HCPCS:

S2140

Cord blood harvesting for transplantation, allogeneic

S2142

Cord blood-derived stem-cell transplantation, allogeneic

S2150

Bone marrow or blood-derived peripheral stem-cell harvesting and transplantation, allogeneic or autologous, including pheresis, high-dose chemotherapy, and the number of days of post-transplant care in the global definition (including drugs; hospitalization; medical surgical, diagnostic and emergency services)               

REFERENCES:

  1. Al Khabori M, de Almeida JR, Guyatt GH et al. Autologous stem cell transplantation in follicular lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst 2012; 104(1):18-28.

  2. Armitage JO.  Allotransplants for mantle cell lymphoma.  Ann Oncol 2002; 13(suppl 2):9a.

  3. Baldissera RC, Nucci M, Vigorito AC, et al. Frontline therapy with early intensification and autologous stem cell transplantation versus conventional chemotherapy in unselected high-risk, aggressive non-Hodgkin's lymphoma patients: A prospective randomized GEMOH report. Acta Haematol 2006; 115(1-2):15-21.

  4. Banks PM, Chan J, Cleary ML, et al. Mantle cell lymphoma. A proposal for unification of morphologic, immunologic, and molecular data. Am J Surg Pathol 1992; 16(7):637-640.

  5. Betticher DC, Martinelli G, Radford JA, et al. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: Results of the international randomized phase III trial (MISTRAL). Ann Oncol 2006; 17(10):1546-1552.

  6. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Autologous bone marrow transplantation for the treatment of non-Hodgkin’s lymphoma. TEC Evaluations 1987; Volume 2, p. 61.

  7. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Allogeneic bone marrow transplantation (BMT) in the treatment of Hodgkin’s disease (lymphoma) and non-Hodgkin’s lymphoma. TEC Evaluations 1990; Volume 5, p. 178.

  8. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). High-dose chemotherapy with autologous stem-cell support or allogeneic stem-cell support for follicular non-Hodgkin’s lymphoma. TEC Assessments 1995; Volume 10, Tab 28.

  9. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Salvage high-dose chemotherapy with allogeneic stem-cell support for relapse or incomplete remission following high-dose chemotherapy with autologous stem-cell transplantation for hematologic malignancies. TEC Assessments 2000; Volume 15, Tab 9.

  10. Bozkaya Y, Uncu D, Dagdas S, et al. Evaluation of lymphoma patients receiving high-dose therapy and autologous stem cell transplantation: experience of a single center. Indian J Hematol Blood Transfus. Sep 2017; 33(3):361-369.

  11. Casasnovas RO, Ysebaert L, Thieblemont C, et al. FDG-PET-driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study. Blood. Sep 14 2017; 130(11):1315-1326.

  12. Cornell RF, Bachanova V, D'Souza A, et al. Allogeneic Transplantation for Relapsed Waldenstrom Macroglobulinemia and Lymphoplasmacytic Lymphoma. Biol Blood Marrow Transplant. Jan 2017; 23(1): 60-66.

  13. Corradini P, Dodero A, Zallio F et al. Graft-versus lymphoma effect in relapsed peripheral T-cell non-Hodgkin’s lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells. J Clin Oncol 2004; 22(11):2172-2176.

  14. Corradini P, Tarella C, Zallio F et al. Long-term follow-up of patients with peripheral T-cell lymphoma treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation. Leukemia 2006; 20(9):1533-1538.

  15. Crocchiolo R, Castagna L, Furst S et al. Tandem autologous-allo-SCT is feasible in patients with high-risk relapsed non-Hodgkin's lymphoma. Bone Marrow Transplant 2013; 48(2):249-252.

  16. Dearden CE, Johnson R, Pettengell R et al. Guidelines for the management of mature T-cell and NK-cell neoplasms (excluding cutaneous T-cell lymphoma). Br J Haematol 2011; 153(4):451-485.

  17. Deconinck E, Foussard C, Milpied N, et al.  High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS.  Blood 2005; 105(10):3817-3823.

  18. Dreyling M, Lenz G, Hoster E, et al.  Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression free survival in mantle-cell lymphoma: Results of a prospective randomized trial of the European MCL network.  Blood 2005; 105(7):2677-2684.

  19. Evens AM, Winter JN, Hou N, et al.  A phase II clinical trial of intensive chemotherapy followed by consolidative stem cell transplant: Long-term follow-up in newly diagnosed mantle cell lymphoma.  Br J Haematol 2008; 140(4):385-393.

  20. Fisher RI.  Autologous bone marrow transplantation for aggressive non-Hodgkin’s lymphoma: Lessons learned and challenges remaining.  J Natl Cancer Inst 2001; 93(1):4-5.

  21. Fisher RI.  Autologous stem-cell transplantation as a component of initial treatment for poor-risk patients with aggressive non-Hodgkin's lymphoma: Resolved issues versus remaining opportunity.  J Clin Oncol 2002; 20(22):4411-4412.

  22. Garcia-Noblejas A, Cannata-Ortiz J, Conde E, et al. Autologous stem cell transplantation (ASCT) in patients with mantle cell lymphoma: a retrospective study of the Spanish lymphoma group (GELTAMO). Ann Hematol. Aug 2017; 96(8):1323-1330.

  23. Geisler C. Mantle cell lymphoma: are current therapies changing the course of the disease? Curr Oncol Rep 2009; 11(5):371-377.

  24. Geisler CH, Kolstad A, Laurell A, et al.  Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.  Blood 2008; 112(7):2687-2693.

  25. Greb A, Bohlius J, Schiefer D, et al.  High-dose chemotherapy with autologous stem cell transplantation in the first line treatment of aggressive non-Hodgkin lymphoma (NHL) in adults.  Cochrane Database Syst Review 2008 Jan 23; (1):CD004024.

  26. Hahn T, Wolff SN, Czuczman M, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of diffuse large cell B-cell non-Hodgkin's lymphoma: an evidence-based review. Biol Blood Marrow Transplant 2001; 7(6):308-331.

  27. Haioun C, Lepage E, Gisselbrecht C, et al. Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. J Clin Oncol 1997; 15(3):1131-1137.

  28. Haioun C, Lepage E, Gisselbrecht C, et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a Groupe d'Etude des Lymphomes de l'Adulte study. J Clin Oncol 2000; 18(16):3025-3030.

  29. Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol. Dec 1999; 10(12):1419-1432.

  30. Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: A proposal from the international lymphoma study group. Blood 1994; 84(5):1361-1392.

  31. Hosing C, Champlin RE. Stem-cell transplantation in T-cell non-Hodgkin’s lymphomas. Ann Oncol 2011; 22(7):1471-1477.

  32. Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 2008; 111:558-565.

  33. Jacobsen ED, Kim HT, Ho VT et al. A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sézary syndrome. Ann Oncol 2011 22(7):1608-1613.

  34. Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program 2009:523-531.

  35. Jimenez-Ubieto A, Grande C, Caballero D, et al. Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure who reach complete response after rescue treatment. Hematol Oncol. 2018 Dec; 36(5). 

  36. Kaiser U, Uebelacker I, Abel U, et al.  Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma.  J Clin Oncol 2002; 20(22):4413-4419.

  37. Kapoor P, Ansell SM, Fonseca R, et al. Diagnosis and Management of Waldenstrom Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines 2016. JAMA Oncol. Sep 01 2017; 3(9): 1257-1265.

  38. Kasamon YL. Blood or marrow transplantation for mantle cell lymphoma. Curr Opin Oncol 2007; 19:128-135.

  39. Kewalramani T, Zelenetz AD, Teruya-Feldstein J et al. Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma. Br J Haematol 2006; 134(2):202-207.

  40. Khouri IF, Lee MS, Romaguera J, et al. Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versus-malignancy.  Ann Oncol 1999; 10:1293-1299.

  41. Khouri IF, Lee MS, Saliba RM, et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol 2003; 21:4407-4412.

  42. Kimby E, Brandt L, Nygren P, et al. A systematic overview of chemotherapy effects in aggressive non-Hodgkin's lymphoma. Acta Oncol 2001; 40(2-3):198-212.

  43. Kluin-Nelemans HC, Zagonel V, Anastasopoulou A, et al. Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: Randomized phase III EORTC study. J Natl Cancer Inst 2001; 93(1):22-30.

  44. Kyriakou C, Canals C, Cornelissen JJ, et al. Allogeneic stem-cell transplantation in patients with Waldenstrom macroglobulinemia: report from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. JClin Oncol. Nov 20 2010; 28(33): 4926-34.

  45. Kyriakou C, Canals C, Finke J et al. Allogeneic stem cell transplantation is able to induce long-term remissions in angioimmunoblastic T-cell lymphoma: a retrospective study from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2009; 27(24):3951-3958.

  46. Kyriakou C, Canals C, Sibon D, et al. High-dose therapy and autologous stem-cell transplantation in Waldenstrom macroglobulinemia: the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol.May 01 2010; 28(13): 2227-32.

  47. Ladetto M, De Marco F, Benedetti F, et al. Prospective, multicenter randomized GITMO/IIL trial comparing intensive R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: The superior disease control of R-HDS does not translate into an overall survival advantage. Blood 2008; 111(8):4004-4013.

  48. Laport GG. The role of hematopoietic cell transplantation for follicular non-Hodgkin’s lymphoma. Biol Blood Marrow Transplant 2006; 12:59-65.

  49. Leblond V, Kastritis E, Advani R, et al. Treatment recommendations from the Eighth International Workshop on Waldenstrom’s Macroglobulinemia. Blood. Sep 08 2016; 128(10): 1321-8.

  50. Le Gouill S, Milpied N, Buzyn A et al. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Société Française de Greffe de Moëlle et de Thérapie Cellulaire. J Clin Oncol 2008; 26(14):2264-2271.

  51. Lenz G, Dreyling M, Schiegnitz E, et al. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low Grade Lymphoma Study Group. Blood 2004; 104(9):2667-2674.

  52. Mamez AC, Dupont A, Blaise D, et al. Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285patients from the Societe Francophone de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC). J Hematol Oncol. May 19 2020; 13(1): 56.

  53. Maris MB, Sandmaier BM, Storer BE, et al. Allogeneic hematopoietic cell transplantation after fludarabine and two Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood 2004; 104:3535-3542.

  54. Mercadal S, Briones J, Xicoy B et al. Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma. Ann Oncol 2008; 19(5):958-963.

  55. Monjanel H, Deconinck E, Perrodeau E et al. Long-term follow-up of tandem high-dose therapy with autologous stem cell support for adults with high-risk age-adjusted international prognostic index aggressive non-Hodgkin lymphomas: A GOELAMS pilot study. Biol Blood Marrow Transplant 2011; 17(6):935-940.

  56. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas. Version 7.2017. www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed January 2, 2018.

  57. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: T-Cell Lymphomas. Version 2.2018. www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf. Accessed January 2, 2018.

  58. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Non-Hodgkin’s Lymphomas, v.5.2014. www.nccn.org/professionals/physician_gls/PDF/nhl.pdf. Accessed December 12, 2014.

  59. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Non- Hodgkin'sLymphomas. Version 2.2015. https://www2.tri-kobe.org/nccn/guideline/hematologic/nhl/english/nhl.pdf. Accessed November 22, 2020.

  60. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas. Version 4.2020. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed November 21, 2020.

  61. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic Lymphoma. Version 1.2021.https://www.nccn.org/professionals/physician_gls/pdf/waldenstroms.pdf. Accessed January 4, 2021.

  62. National Cancer Institute. Adult Non-Hodgkin Lymphoma Treatment (PDQ®)-Health Professional Version. 2017; http://www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/healthprofessional. Accessed January 2, 2018.

  63. Olivieri A, Santini G, Patti C, et al. Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: Long-term results by the NHLCSG. Ann Oncol 2005; 16(12):1941-1948.

  64. Papadopoulos KP, Noguera-Irizarry W, Wiebe L, et al. Pilot study of tandem high-dose chemotherapy and autologous stem cell transplantation with a novel combination of regimens in patients with poor risk lymphoma. Bone Marrow Transplant 2005 Sep; 36(6):491-497.

  65. Philip T and Biron P. High-dose chemotherapy and autologous bone marrow transplantation in diffuse intermediate- and high-grade non-Hodgkin lymphoma. Crit Rev Oncol Hematol 2002; 41(2):213-223.

  66. Philip T, Guglielmi C, Hagenbeek A et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med 1995; 333(23):1540-1545.

  67. Physician Data Query (PDQ®). Adult non-Hodgkin lymphoma treatment. Modified 03/03/2008. www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/healthprofessional.

  68. Qualls D, Sullivan A, Li S, et al. High-dose thiotepa, busulfan, cyclophosphamide, and autologous stem cell transplantation as upfront consolidation for systemic non-Hodgkin lymphoma with synchronous central nervous system involvement. Clin Lymphoma Myeloma Leuk. Dec 2017; 17(12):884-888.

  69. Reimer P, Rüdiger T, Geissinger E, et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol 2009; 27(1):106-113.

  70. Reimer P. Impact of autologous and allogeneic stem cell transplantation in peripheral T-cell lymphomas. Adv Hematol 2010; 2010:320624.

  71. Rodriguez J, Conde E, Gutierrez A et al. The adjusted International Prognostic Index and beta-2-microglobulin predict the outcome after autologous stem cell transplantation in relapsing/refractory peripheral T-cell lymphoma. Haematologica 2007; 92(8):1067-1074.

  72. Rodriguez J, Conde E, Gutierrez A, et al. Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: A prospective study from The Gel-Tamo Study Group. Eur J Haematol 2007; 79(1):32-38.

  73. Rodriguez J, Gutierrez A, Martínez-Delgado B et al. Current and future aggressive peripheral T-cell lymphoma treatment paradigms, biological features and therapeutic molecular targets. Crit Rev Oncol Hematol 2009; 71(3):181-198.

  74. Satwani P, Jin Z, Martin PL, et al. Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma. Leukemia. Feb 2015; 29(2): 448-55.

  75. Schaaf M, Reiser M, Borchmann P et al. High-dose therapy with autologous stem cell transplantation versus chemotherapy or immuno-chemotherapy for follicular lymphoma in adults. Cochrane Database Syst Rev 2012; 1:CD007678.

  76. Schouten HC, Qian W, Kvaloy S, et al. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin’s lymphoma: results from the randomized European CUP trial. J Clin Oncol 2003; 21:3918-3927.

  77. Sebban C, Mounier N, Brousse N, et al. Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: The GELF-94 randomized study from the Groupe d’Etude des Lymphomes de l’Adulte (GELA). Blood 2006; 108:2540-2544.

  78. Solal-Celigny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index. Blood 2004; 104(5):1258-1265.

  79. Song KW, Mollee P, Keating A et al. Autologous stem cell transplant for relapsed and refractory peripheral T-cell lymphoma: variable outcome according to pathological subtype. Br J Haematol 2003; 120(6):978-985.

  80. Stiff PJ, Unger JM, Cook JR et al. Autologous transplantation as consolidation for aggressive non- Hodgkin's lymphoma. N Engl J Med 2013; 369(18):1681-1690.

  81. Strubmann T, Fritsch K, Baumgarten A, et al. Favourable outcomes of poor prognosis diffuse large B-cell lymphoma patients treated with dose-dense rituximab, high-dose methotrexate and six cycles of CHOP-14 compared to first-line autologous transplantation. Br J Haematol. Sep 2017; 178(6):927-935.

  82. Sweetenham JW, Santini G, Qian W, et al. High-dose therapy and autologous stem-cell transplantation versus conventional-dose consolidation/maintenance therapy as postremission therapy for adult patients with lymphoblastic lymphoma: Results of a randomized trial of the European Group for Blood and Marrow Transplantation and the United Kingdom Lymphoma Group.  J Clin Oncol 2001; 19(11):2927-2936.

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POLICY HISTORY:

Medical Policy Group, September 2009 (3)

Medical Policy Administration Committee, September 2009

Available for comment September 18-November 2, 2009

Medical Policy Panel, February 2011

Medical Policy Group, June 2011 (2): Policy, Key Points, References updated

Medical Policy Administration Committee, July 2011

Available for comment, July 6 through August 22, 2011

Medical Policy Group, December 2011(3): 2012 Code Updates- updated 38208, 38209 and 38230 & added 38232

Medical Policy Group, February 2012 (3): 2012 Updates – Policy, Key Points, References

Medical Policy Panel, February 2013

Medical Policy Group, February 2013 (2):  2013 Updates – Description, Key Points and References; no change in policy statement

Medical Policy Panel, February 2014

Medical Policy Group, February 2014 (3):  2014 Updates to Description, Key Points & References; no change in policy statement

Medical Policy Panel, February 2015

Medical Policy Group, February (2): 2015 Updates to Key Points and Coding; no change to policy statement.

Medical Policy Panel, September 2017

Medical Policy Group, October 2017 (7): 2017 Updates to Description, Key Points, Approved by Governing Bodies, and References. Policy Statement- removed policy info from 2011. No change in intent.

Medical Policy Group, December 2017. Annual Coding Update 2018. Added new CPT code 38222 effective 1/1/18 to the Current Coding section.  Updated verbiage for revised CPT codes 38220 and 38221.

Medical Policy Panel, January 2018

Medical Policy Group, January 2018 (7): 2018 Updates to Key Points and References. No change to Policy Statement.

Medical Policy Panel, January 2019

Medical Policy Group, February 2019 (3): 2019 Updates to Key Points, Practice Guidelines and Position Statements, References and Key Words: added: Diffuse Large B-Cell Lymphoma, DLBCL, Mantle Cell Lymphoma, MCL, Peripheral T-Cell Lymphoma, PTCL, Follicular Lymphoma, Hematopoietic Cell Transplantation, HCT, anaplastic large-cell lymphoma, and ALCL. No changes to policy statement or intent. Removed effective for dates of service language from 2012 in the coding section.

Medical Policy Panel, January 2020

Medical Policy Group, March 2020 (3): 2020 Updates to Description, Key Points, Practice Guidelines and Position Statements, References and Key Words: added: Histiocytic Sarcoma, HS. Added Histiocytic Sarcoma to covered diagnoses table. Added Policy Guidelines section. Available for comment March 5, 2020 through April 18, 2020. No changes to policy statement or intent.

Medical Policy Panel, January 2021

Medical Policy Group, February 2021 (3): 2021 Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. Policy statement added to include critieria for patients with Waldenström Macroglobulinemia for both autologous and allogeneic stem cell transplants. Policy statement updated to remove “not medically necessary, “no other changes to policy statement or intent. Key Words added: Waldenström Macroglobulinemia.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.