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Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

Policy Number: MP-388

Latest Review Date: February 2021

Category: Therapy                                                                 

Policy Grade: B

POLICY:

Allogeneic hematopoietic cell transplantation (HCT) using a myeloablative conditioning regimen may be considered medically necessary to treat:

  • Poor- to intermediate-risk AML in first complete remission (CR1),OR

  • AML that is refractory to standard induction chemotherapy but can be brought into CR with intensified induction chemotherapy; OR

  • AML that relapses following chemotherapy-induced CR1 but can be brought into CR2 or beyond with intensified induction chemotherapy; OR

  • AML in patients, who have relapsed following a prior autologous HSCT, but can be brought into CR with intensified induction chemotherapy and may be medically able to tolerate the procedure.

Allogeneic HCT using a reduced-intensity conditioning regimen may be considered medically necessary as a treatment of AML in patients who are in complete marrow and extramedullary remission (CR1 or beyond), and who for medical reasons would be unable to tolerate a myeloablative conditioning regimen.

Autologous HCT may be considered medically necessary to treat AML in first or second remission or relapsed AML if responsive to intensified induction chemotherapy in patients who are not candidates for allogeneic HCT. 

Allogeneic and autologous HCT are investigational in patients not meeting any of the above criteria.

POLICY GUIDELINES:

Cord blood is discussed in greater detail in medical policy # 439 Placenta/Umbilical Cord Blood as a Source of Stem Cells.

Primary refractory acute myeloid leukemia (AML) is defined as leukemia that does not achieve a complete remission after conventionally dosed (nonmarrow ablative) chemotherapy.

In the French-American-British criteria, the classification of AML is solely based on morphology as determined by the degree of differentiation along different cell lines and the extent of cell maturation.

Clinical features that predict poor outcomes of AML therapy include, but are not limited to, the following:

  • Treatment-related AML (secondary to prior chemotherapy and/or radiotherapy for another malignancy)

  • AML with antecedent hematologic disease (eg, myelodysplasia)

  • Presence of circulating blasts at the time of diagnosis

  • Difficulty in obtaining first complete remission with standard chemotherapy

  • Leukemias with monocytoid differentiation (French-American-British classification M4 or M5).

The newer, currently preferred, World Health Organization classification of AML incorporates and interrelates morphology, cytogenetics, molecular genetics, and immunologic markers. It attempts to construct a classification that is universally applicable and prognostically valid. The World Health Organization system was adapted by National Comprehensive Cancer Network to estimate individual patient prognosis to guide management, as shown in Table PG1.

Table PG1. Risk Status of AML Based on Cytogenetic and Molecular Factors

Risk Status

Cytogenetic Factors

Molecular Abnormalities

Favorable

Inv16, t(8;21), t(16;16)

Normal cytogenetics with isolated NPM1 variant

Intermediate

Normal

+8 only, t(9;11) only

Other abnormalities not listed with better-risk and poor-risk cytogenetics

c-KIT variant in patients with t(8;21) or inv16

Poor

Complex (³3 abnormalities)

-5, -7, 5q-, 7q-, +8, inv3, t(3;3), t(6;9), t(9;22)

Abnormalities of 11q23, excluding t(9;11)

Normal cytogenetics with isolated FLT3-ITD variant

AML: acute myeloid leukemia; ITD: internal tandem duplication.

The relative importance of cytogenetic and molecular abnormalities in determining prognosis and guiding therapy is under investigation.

The ideal allogeneic donors are human leukocyte antigen‒identical siblings, matched at the human leukocyte antigen-A, -B, and -DR loci (6 of 6). Related donors mismatched at 1 locus are also considered suitable donors. A matched, unrelated donor identified through the National Marrow Donor Registry is typically the next option considered. Recently, there has been interest in haploidentical donors, typically a parent or a child of the patient, for which there usually is sharing of only three of the six major histocompatibility antigens. Most patients will have such a donor; however, the risk of graft-versus-host disease and overall morbidity of the procedure may be severe, and experience with these donors is not as extensive as that with matched donors.

DESCRIPTION OF PROCEDURE OR SERVICE:

Acute myeloid leukemia (AML) (also called acute nonlymphocytic leukemia) refers to leukemia’s that arise from a myeloid precursor in the bone marrow.  There is a high incidence of relapse, which has prompted research into a variety of post-remission strategies using either allogeneic or autologous hematopoietic cell transplantation (HCT). HCT refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of drugs with or without whole body radiotherapy.

Treatment

Complete remissions can be achieved initially using induction therapy, consisting of conventional doses of combination chemotherapy. A complete response is achieved in 60 - 80% of adults younger than 60 years of age and in 40 – 60% in patients older than 60 years of age. However, the high incidence of disease relapse has prompted research into a variety of post remission (consolidation) strategies, typically using high-dose chemotherapy with autologous HCT or high-dose or reduced-intensity chemotherapy with allogeneic HCT. The two treatments - autologous HCT and allogeneic HCT - represent two different strategies. The first, autologous HCT is a “rescue” but not therapeutic procedure; the second, allogeneic HCT is a “rescue” plus therapeutic procedure.

Hematopoietic Cell Transplantation

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

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 a critical factor for achieving a good outcome of allogeneic HCT. Immunologic compatibility is established by typing human leukocyte antigens (HLA) 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).

Conventional Conditioning for HCT

The conventional practice of allo-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 (GVM) 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 GVM 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 pre-engraftment opportunistic infections secondary to loss of endogenous bone marrow function and organ damage and failure caused by the cytotoxic drugs. Furthermore, in any allo-HCT, immunosuppressant drugs are required to minimize graft rejection and GVHD, which also increase susceptibility to opportunistic infections. The immune reactivity between donor T -cells and malignant cells is responsible for the GVM effect; it also leads to acute and chronic GVHD.

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 prior to undergoing bone marrow ablation. Therefore, autologous HCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous HCT are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment, but not GVHD.

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 two-fold: to reduce disease burden, and to minimize treatment-related morbidity and nonrelapse mortality in the period during which the beneficial GVM 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 allo-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 this evidence review, RIC refers to all conditioning regimens intended to be nonmyeloablative, as opposed to fully myeloablative (conventional) regimens.

KEY POINTS:

The most recent literature review was performed through December 1, 2020.

Summary of Evidence

For individuals who have cytogenetic or molecular intermediate- or poor-risk acute myeloid leukemia (AML) in first complete remission who receive allogeneic hematopoietic cell transplantation (allo-HCT) with myeloablative conditioning, the evidence includes randomized controlled trials (RCTs) and matched cohort studies. Relevant outcomes are overall survival (OS) and disease-specific survival. The evidence has revealed that allo-HCT is better at improving overall and disease-specific survival rates in patients with AML in first complete remission than conventional chemotherapy. All trials employed natural randomization based on donor availability and an intention-to-treat analysis. Survival rates appear to be associated with presence of minimal residual disease and risk category. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have AML refractory to standard induction chemotherapy who receive allo-HCT with MAC, the evidence includes retrospective data compiled from patients entered in phase 3 trials and registry data. Relevant outcomes are overall survival and disease-specific survival. The evidence would suggest that allo-HCT improves overall and disease-specific survival rates in patients who are refractory to induction chemotherapy better than conventional chemotherapy. While there are some limitations to the evidence, which include its retrospective nature, lack of rigorous randomization, and general pitfalls of registry data, these results may provide clinically meaningful benefit for patients who do not have other treatment options. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have AML who relapsed after standard induction chemotherapy-induced first complete remission who receive allo-HCT or autologous HCT with myeloablative conditioning, the evidence includes retrospective data compiled from patients entered in phase 3 trials and registry data. Relevant outcomes are OS and disease-specific survival. The evidence has shown that allo-HCT improves OS rates in patients with relapsed AML better than conventional chemotherapy. Limitations of the evidence include its retrospective nature, lack of rigorous randomization, and pitfalls of registry data. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have cytogenetic or molecular intermediate- or poor-risk AML in first complete remission and for medical reasons cannot tolerate myeloablative conditioning who receive allo-HCT with reduced-intensity conditioning, the evidence includes two RCTs and other comparative and noncomparative studies. Relevant outcomes are OS, disease-specific survival, and treatment-related morbidity. The RCTs compared reduced-intensity conditioning with myeloablative conditioning and reported similar rates in nonrelapse mortality, relapse, and OS though one of the trials was stopped prematurely due to a slow accrual of patients. Two retrospective comparative studies found no difference in OS or leukemia-free survival between the conditioning regimens. It appears unlikely that additional comparative evidence will be generated. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have AML in first complete remission or beyond without a suitable allo-HCT donor who receive autologous HCT, the evidence includes prospective cohort studies in which patients with an available sibling donor were offered allo-HCT (biologic randomization) with random assignment of all others to autologous HCT or chemotherapy (or no further treatment); and randomized trials comparing autologous HCT with chemotherapy in all patients. Relevant outcomes are OS and disease-specific survival. Compared with chemotherapy, patients undergoing autologous HCT experienced reduced relapse and improved disease-free survival rates. OS did not differ between the groups. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network

The National Comprehensive Cancer Network clinical guidelines (v.2. 2021) for acute myeloid leukemia state that allo-HCT is recommended for patients aged <60 years after standard-dose cytarabine induction with induction failure or significant residual disease without a hypocellular marrow. It is also recommended after high-dose cytarabine induction with induction failure, or as post-remission therapy in those with intermediate-risk or poor-risk cytogenetics. Allo-HCT is identified as a "reasonable option" for patients aged ≥60 years after standard-dose cytarabine induction with residual disease or induction failure or following complete response (preferably in a clinical trial). In addition, allo-HCT is recommended for relapsed or refractory disease.

According to the guidelines, the role of autologous HCT is diminishing due to improvements in allo-HCT that have expanded the pool of potential donors outside the family setting. Autologous HCT should not be a recommended consolidation therapy outside the setting of a clinical trial.

U.S. Preventive Services Task Force Recommendations

Not Applicable.

KEY WORDS:

Bone Marrow Transplant, High-Dose Chemotherapy, Acute Myeloid Leukemia (AML), Stem-Cell Transplant, HSCT, Hematopoietic Cell Transplant, HCT

APPROVED BY GOVERNING BODIES:

The U.S. Food and Drug Administration regulate human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, 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

; biopsy (ies)

38222

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

38230

Bone marrow harvesting for transplantation; allogeneic

38232   

Bone marrow harvesting for transplantation; autologous

38240

Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor

38241

; autologous transplantation

38242

Allogeneic donor lymphocyte infusions

 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. Abdul-Washid SF, Ismail NA, Mohd-Idris MR, et al. Comparison of reduced-intensity and myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and acute lymphoblastic leukemia: a meta-analysis. Stem Cells Dev. Nov 1 2014; 23(21):2535-2552.

  2. Baer MR and Greer JP. Acute myeloid leukemia in adults. In: Greer JP, Foerster J, Rodgers GM, et al. (eds.). Wintrobe’s Clinical Hematology. Philadelphia, Lippincott Williams & Wilkins, 2009 1843-1888.

  3. Bitan M, He W, Zhang MJ, et al. Transplantation for children with acute myeloid leukemia: a comparison of outcomes with reduced intensity and myeloablative regimens. Blood. Mar 6, 2014; 123(10):1615-1620.

  4. Blaise D, Vey N, Faucher C, et al. Current status of reduced intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica 2007; 92(4):533-541.

  5. Blum WG, Mims AS. Treating acute myeloid leukemia in the modern era: A primer. Cancer. Aug 07 2020.

  6. Bornhauser M, Kienast J, Trenschel R et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomized phase 3 trial. Lancet Oncol 2012; 13(10): 1035-1044.

  7. Brandwein JM, Zhu N, Kumar R, et al. Treatment of older patients with acute myeloid leukemia (AML): revised Canadian consensus guidelines. Am J Blood Res. Jul 2017; 7(4):30-40.

  8. Breems DA, van Putten WL, Huijgens PC, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol 2005; 23(9):1969-1978.

  9. Breems DA and Lowenberg B. Acute myeloid leukemia and the position of autologous stem cell transplantation. Semin Hematol 2007; 44(4):259-266.

  10. Buckley SA, Wood BL, Othus M, et al. Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis. Haematologica. May 2017; 102(5):865-873.

  11. Canaani J, Labopin M, Socie G, et al. Long term impact of hyperleukocytosis in newly diagnosed acute myeloid leukemia patients undergoing allogeneic stem cell transplantation: An analysis from the acute leukemia working party of the EBMT. Am J Hematol. Jul 2017; 92(7):653-659.

  12. Cornelissen JJ, van Putten WL, Verdonck LF, et al. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: Benefits for whom? Blood 2007; 109(9):3658-3666.

  13. Craddock CF. Full-intensity and reduced-intensity allogeneic stem cell transplantation in AML. Bone Marrow Transplant 2008; 41(5):415-423.

  14. De Latour RP, Porcher R, Dalle JH, et al. Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: The European Group for Blood and Marrow Transplantation experience. Blood. 2013; 122(26):4279-4286.

  15. Deschler B, de Witte T, Mertelsman R, et al. Treatment decision-making for older patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: Problems and approaches. Haematologica 2006; 91(11):1513-1522.

  16. Devine SM, Owzar K, Blum W, et al. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. Dec 10 2015; 33(35):4167-4175.

  17. Dholaria B, Savani BN, Hamilton BK, et al. Hematopoietic Cell Transplantation in the Treatment of Newly Diagnosed Adult Acute Myeloid Leukemia: An Evidence-Based Review from the American Society of Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. Sep 20 2020.

  18. Dohner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. Sep 17 2015; 373(12):1136-1152.

  19. Estey EH. Treatment of acute myeloid leukemia. Haematologica 2009; 94(1): 10-16.

  20. Food and Drug Administration (FDA). Tissues and Tissue Products. www.fda.gov/BiologicsBloodVaccines/TissueTissueProducts/.

  21. Frazer J, Couban S, Doucette S, et al. Characteristics predicting outcomes of allogeneic stem-cell transplantation in relapsed acute myelogenous leukemia. Curr Oncol. Apr 2017; 24(2):e123-e130.

  22. Gratwohl A, Baldomero H, Frauendorfer K, et al. Results of the EBMT activity survey 2005 on haematopoietic stem cell transplantation: Focus on increasing use of unrelated donors. Bone Marrow Transplant 2007; 39(2):71-87.

  23. Greer JP, Foerster J, Rodgers GM, et al. Acute myeloid leukemia in adults. Philadelphia: Lippincott Williams & Wilkins; 2009. Wintrobe’s Clinical Hemotology.

  24. Gyurkocza B, Storb R, Storer BE, et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. Jun 10 2010; 28(17):2859-2867.

  25. Hamadani M, Awan FT and Copelan EA. Hematopoietic stem cell transplantation in adults with acute myeloid leukemia. Biol Blood Marrow Transplant 2008; 14(5):556-567.

  26. Hamadani M, Mohty M. Kharfan-Dabaja MA. Reduced-intensity conditioning allogeneic hematopoietic cell transplantation in adults with acute myeloid leukemia. Cancer Control 2011; 18(4):237-245.

  27. Hamidieh AA, Alimoghaddam K, Jahani M, et al. Non-TBI hematopoietic stem cell transplantation in pediatric AML patients: a single-center experience. J Pediatr Hematol Oncol. Aug 2013; 35(6):e239-245.

  28. Heidrich K, Thiede C, Schafer-Eckart K, et al. Allogeneic hematopoietic cell transplantation in intermediate risk acute myeloid leukemia negative for FLT3-ITD, NPM1- or biallelic CEBPA mutations. Ann Oncol. Nov 1 2017; 28(11):2793-2798.

  29. Hubel K. Weingart O, Naumann F et al. Allogeniec stem cell transplant in adult patients with acute myelogenous leukemia: a systematic analysis of international guidelines and recommendations. Leuk Lymphoma 2011; 52(3):444-457.

  30. Huisman C, Meijer E, Petersen EJ, et al.  Hematopoietic stem cell transplantation after reduced intensity conditioning in acute myelogenous leukemia patients older than 40 years. Biol Blood Marrow Transplant 2008; 14(2):181-186.

  31. Koenig K, Mims A, Levis MJ, et al. The Changing Landscape of Treatment in Acute Myeloid Leukemia. Am Soc Clin Oncol Educ Book. Mar 2020; 40: 1-12.

  32. Koreth J, Schlenk R, Kopecky KF, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: Systematic review and meta-analysis of prospective clinical trials. JAMA 2009; 301(22): 2349-2361.

  33. Lee CJ, Savani BN, Mohty M, et al. Haploidentical hematopoietic cell transplantation for adult acute myeloid leukemia: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. Nov 2017; 102(11):1810-1822.

  34. Li D, Wang L, Zhu H, et al. Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Intermediate-Risk Acute Myeloid Leukemia Adult Patients in First Complete Remission: A meta-analysis of Prospective Studies. PLoS One. 2015; 10(7):e0132620.

  35. Lim Z, Brand R, Martino R, et al. Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol 2010; 28(3): 405-411.

  36. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. Nov 2015; 21(11): 1863-1869.

  37. Master S, Mansour R, Devarakonda SS, et al. Predictors of Survival in Acute Myeloid Leukemia by Treatment Modality. Anticancer Res. Apr 2016; 36(4):1719-1727.

  38. McClune BL, Weisdorf DJ, Pedersen TL, et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol 2010; 28(11): 1878-1887.

  39. Miyamoto T, Nagafuji K, Fujisaki T, et al. Prospective randomization of post-remission therapy comparing autologous peripheral blood stem cell transplantation versus high-dose cytarabine consolidation for acute myelogenous leukemia in first remission. Int J Hematol. Apr 2018; 107(4):468-477. 

  40. Mrozek K and Bloomfield CD. Chromosome aberrations, gene mutations and expression changes, and prognosis in adult acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2006; 169-177.

  41. Nathan PC, Sung L, Crump M, et al. Consolidation therapy with autologous bone marrow transplantation in adults with acute myeloid leukemia: a meta-analysis. J Natl Cancer Inst 2004; 96(1):38-45.

  42. National Comprehensive Cancer Network. Acute Myeloid Leukemia.  Clinical Practice Guidelines in Oncology, v3.2017. https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed December 21, 2017.

  43. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: Acute myeloid leukemia. Version 3.2018. https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf. Accessed November 9, 2018.

  44. National Cancer Institute, Surveillance Epidemiology and End Results Program. Cancer Stat Facts: Leukemia - Acute Myeloid Leukemia (AML). n.d.; https://seer.cancer.gov/statfacts/html/amyl.html. Accessed January 8, 2018.

  45. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: acute myeloid leukemia. Version 2.2020. https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Updated September 3, 2019. Accessed November 30, 2019.

  46. Oliansky DM, Appelbaum F, Cassileth PA, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in adults: an evidence-based review. Biol Blood Marrow Transplant 2008; 14(2):137-180.

  47. Paschka P, Marcucci G, Ruppert AS, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv (16) and t (8; 21): a Cancer and Leukemia Group B study. J Clin Oncol 2006; 24(24):3904-3911.

  48. Peffault de Latour R, Porcher R, Dalle JH, et al. Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: the European Group for Blood and Marrow Transplantation experience. Blood. Dec 19 2013; 122(26):4279-4286. 

  49. Pemmaraju N, Tanaka MF, Ravandi F, et al. Outcomes in patients with relapsed or refractory acute promyelocytic leukemia treated with or without autologous or allogeneic hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk. Aug 2013; 13(4):485-492.

  50. Rashidi A, Ebadi M, Colditz GA, et al. Outcomes of Allogeneic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-analysis. Biol Blood Marrow Transplant. Apr 2016; 22(4):651-657.

  51. Ringden O, Erkers T, Aschan J, et al. A prospective randomized toxicity study to compare reduced-intensity and myeloablative conditioning in patients with myeloid leukemia undergoing allogeneic haematopoietic stem cell transplantation. J Intern Med. Aug 2013; 274(2):153-162.

  52. Scherwath A, Schirmer L, Kruse M, et al. Cognitive functioning in allogeneic hematopoietic stem cell transplantation recipients and its medical correlates: a prospective multicenter study. Psychooncology. Jul 2013; 22(7):1509-1516.

  53. Schlenk RF, Dohner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008; 358(18):1909-1918.

  54. Shayegi N, Kramer M, Bornhauser M, et al. The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML. Blood. Jul 4 2013; 122(1):83-92.

  55. Shimoni A, Labopin M, Savani B, et al. Long-term survival and late events after allogeneic stem cell transplantation from HLA-matched siblings for acute myeloid leukemia with myeloablative compared to reduced-intensity conditioning: a report on behalf of the acute leukemia working party of European Group for Blood and Marrow Transplantation. J Hematol Oncol. Nov 08 2016; 9(1):118.

  56. Stelljes M, Krug U, Beelen DW et al. Allogeneic transplantation versus chemotherapy as post remission therapy for acute myeloid leukemia: a prospective matched pair’s analysis. J Clin Oncol. Feb 1 2014; 32(4):288-296.

  57. Stone RM, O’Donnell MR and Sekeres MA. Acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2004; 98-117.

  58. Valcarcel D and Martino R. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and acute myelogenous leukemia. Current Opin Oncol 2007; 19(6):660-666.

  59. Valcarcel D, Martino R, Caballero D, et al. Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: Chronic graft-versus-host disease is the strongest factor improving survival. J Clin Oncol 2008; 26(4):577-584.

  60. Vellenga E, van Putten W, Ossenkoppele GJ et al. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood 2011; 118(23):6037-6042.

  61. Wang J, Ouyang J, Zhou R et al. Autologous hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission: a meta-analysis of randomized trials. Acta Haematol 2010; 124(2):61-71.

  62. Yanada M, Matsuo K, Emi N, et al. Efficacy of allogeneic hematopoietic stem cell transplantation depends on cytogenetic risk for acute myeloid leukemia in first disease remission: A metaanalysis. Cancer 2005; 103(8):1652-1658.

POLICY HISTORY:

Medical Policy Group, September 2009 (3)

Medical Policy Administration Committee, September 2009

Available for comment September 18-November 2, 2009

Medical Policy Group, June 2010 (2)

Medical Policy Panel, August 2011

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

Medical Policy Group, December, 2011 (3): 2012 Code Updates: Updated Codes 38208, 38209, and 38230 and added 38232 effective January 1, 2012

Medical Policy Group, August 2012 (3): 2012 Updates to Key Points and References

Medical Policy Panel, August 2013

Medical Policy Group, August 2013 (3):  2013 Updates to Description, Key Points and References; no change in policy statement

Medical Policy Panel, August 2014

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

Medical Policy Panel, August 2015

Medical Policy Group, October 2015 (2): 2015 Updates to Description, Key Points, Approved by Governing Bodies, Current Coding, and policy statement updated with no change to intent.

Medical Policy Panel, January 2016

Medical Policy Group, February 2016 (2): 2016 Updates to Key Points, Key Words, and References; no change in policy statement.

Medical Policy Panel, July 2017

Medical Policy Group, August 2017 (7): Updates to Key Points, Key Words, and References. Removed “stem” from Policy Statement; 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, February 2018 (7): Updates to Description, Key Points, and References.

Medical Policy Panel, January 2019

Medical Policy Group, February 2019 (3): Updates to Key Points, Practice Guidelines and Position Statements, References and Key Words: added: HCT and Hematopoietic Cell Transplant. Policy statement regarding medical necessity for autologous HCT changed to clarify that it applies to patients that are not candidates for allogeneic HCT. Investigational statements added for patients not meeting MN criteria.

Medical Policy Panel, January 2020

Medical Policy Group, February 2020 (3): 2020 Updates to Description, Key Points, Practice Guidelines and Position Statements, and References.  No changes to policy statement or intent. Policy Guidelines section added to policy.

Medical Policy Panel, January 2021

Medical Policy Group, February 2021 (3): 2021 Updates to Key Points, Practice Guidelines and Position Statements and References. Policy statement updated to remove “not medically necessary, “no other changes to policy statement or intent.

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.