Anthem Blue Cross Connecticut TRANS.00024 Hematopoietic Stem Cell Transplantation for Select Leukemias and Myelodysplastic Syndrome Form

This document addresses hematopoietic stem cell transplantation (HSCT) or hematopoietic cell transplant (HCT) in the treatment of the following select leukemias and myelodysplastic disorders:

• Acute Myeloid Leukemia (AML)
• Acute Lymphoblastic Leukemia (ALL)
• Chronic Myeloid Leukemia (CML)
• Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
• Chronic Myelomonocytic Leukemia (CMML), Myelodysplastic Syndrome (MDS), Myeloproliferative Neoplasms (MPN)
• Myelofibrosis

Note: For umbilical cord transplantation, see TRANS.00016 Umbilical Cord Blood Progenitor Cell Collection, Storage and Transplantation for additional information and criteria.

I.  Acute Myeloid Leukemia (AML)

Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered medically necessary for individuals with AML in any phase of illness after induction when none of the following indicators of a favorable AML classification are present:
   1. Core binding factor (CBF) AML [inv(16) or t(8;21)] with unmutated (wild-type) C-Kit; or
   2. Acute promyelocytic leukemia (APL) t(15;17) in first complete remission; or
   3. Cytogenetically normal AML with FLT3-ITD non-mutated (wild-type) and NPM1 mutated.
2. A repeat allogeneic (ablative or non-myeloablative) stem cell transplantation due to primary graft failure or failure to engraft is considered medically necessary.
3. A second or repeat allogeneic (ablative or non-myeloablative) stem cell transplantation due to relapsed disease is considered medically necessary.

Investigational and Not Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered investigational and not medically necessary for individuals with AML when any of the following indicators of a favorable classification are present:
   1. Core binding factor (CBF) AML [inv(16), t(8;21)] with unmutated (wild-type) C-Kit; or
   2. Acute promyelocytic leukemia (APL) t(15;17) in first complete remission; or
   3. Cytogenetically normal AML with FLT3-ITD non mutated (wild-type) and NPM1 mutated.
2. Autologous stem cell transplantation is considered investigational and not medically necessary for individuals with AML.
3. A second or repeat allogeneic (ablative or non-myeloablative) transplant due to persistent or progressive disease is considered investigational and not medically necessary.
4. Hematopoietic stem cell harvesting for a future but unscheduled transplant is considered investigational and not medically necessary.

II.  Acute Lymphoblastic Leukemia (ALL)

Note: There is no clear age cut-off that distinguishes adult from childhood ALL. Published data generally group outcomes according to whether the individual is treated by an adult or pediatric oncologist.

Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered medically necessary provided the individual has a diagnosis of ALL and one of the following:
   1. Individual is in first complete remission and has one or more of the following "high-risk" factors:
      1. Philadelphia chromosome positive [t(9;22) or BCR-ABL positive];
      2. Any of the following cytogenetic or molecular abnormalities:  t(4;11), t(1;19), t(8;14), del(7q), trisomy 8, 11q23 (MLL) translocation;
      3. Hypodiploidy (less than 44 chromosomes);
      4. B-cell immunophenotype;
      5. Age greater than 15 years;
      6. Leukocyte count greater than 50 x 10⁹/L;
      7. Extramedullary disease (especially central nervous system);
      8. Failure to achieve a complete remission within 6 weeks of the start of induction therapy;
      9. Minimal residual disease (MRD) positivity following induction; or
   2. Individual is in second or subsequent complete remission; or
   3. Individual is in any relapse.
2. A repeat allogeneic (ablative or non-myeloablative) stem cell transplantation due to primary graft failure or failure to engraft is considered medically necessary.

Investigational and Not Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered investigational and not medically necessary for individuals who do not meet the above criteria.
2. A second or repeat allogeneic (ablative or non-myeloablative) transplant due to persistent, progressive or relapsed disease is considered investigational and not medically necessary.
3. Hematopoietic stem cell harvesting for a future but unscheduled transplant is considered investigational and not medically necessary.
4. Autologous stem cell transplant is considered investigational and not medically necessary for individuals with ALL.

III.  Chronic Myeloid Leukemia (CML)

Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered medically necessary for individuals with CML and any of the following indications:
   1. No hematologic response at 3 months; or
   2. No cytogenetic response at 6 months; or
   3. Cytogenetic relapse at 12 or 18 months after achieving initial hematologic remission; or
   4. Partial cytogenetic response at 18 months; or
   5. Individuals with T315-I mutation; or
   6. Individuals in accelerated or blast phase.
2. An allogeneic stem cell transplantation (ablative or non-myeloablative) after a prior autologous stem cell transplantation is considered medically necessary for individuals who meet the above criteria.
   Note: This applies if a previous autologous transplant was performed, regardless if the Position Statement deems autologous stem cell transplantation as investigational and not medically necessary.
3. A repeat allogeneic (ablative or non-myeloablative) stem cell transplantation due to primary graft failure or failure to engraft is considered medically necessary.

Investigational and Not Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered investigational and not medically necessary for individuals who do not meet the above criteria.
2. Autologous stem cell transplantation is considered investigational and not medically necessary.
3. A second or repeat allogeneic (ablative or non-myeloablative) transplant due to persistent, progressive or relapsed disease is considered investigational and not medically necessary.
4. Hematopoietic stem cell harvesting for a future but unscheduled transplant is considered investigational and not medically necessary.

IV.  Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered medically necessary for individuals with CLL or SLL who are refractory to small molecule inhibitor therapy.
2. An allogeneic stem cell transplantation (ablative or non-myeloablative) after a prior autologous stem cell transplantation* is considered medically necessary for individuals with CLL or SLL who meet the above criteria.
   *Note: This applies if a previous autologous transplant was performed, regardless if the Position Statement deems autologous stem cell transplantation as investigational and not medically necessary.
3. A repeat allogeneic (ablative or non-myeloablative) stem cell transplantation due to primary graft failure or failure to engraft is considered medically necessary.

Investigational and Not Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered investigational and not medically necessary for individuals with CLL or SLL who do not meet the above criteria.
2. Autologous stem cell transplantation in individuals with CLL or SLL is considered investigational and not medically necessary.
3. A second or repeat allogeneic (ablative or non-myeloablative) transplant due to persistent, progressive or relapsed disease is considered investigational and not medically necessary.
4. Hematopoietic stem cell harvesting for a future but unscheduled transplant is considered investigational and not medically necessary.

V.  Myelodysplastic Syndromes (MDS) including Myelodysplastic/Myeloproliferative neoplasms (MDS/MPN)

Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered medically necessary for individuals who have chronic myelomonocytic leukemia (CMML) or a de novo or primary myelodysplastic syndrome with an intermediate International Prognostic Scoring System (IPSS) score of 1.5-2.0 or a high IPSS score of greater than or equal to 2.5 or a Revised IPSS (IPSS-R) intermediate score of greater than 3.5 or a high or very high IPSS-R score. Individuals may have the allogeneic transplant as initial therapy.* 
2. Allogeneic (ablative and non-myeloablative) stem cell transplantation is considered medically necessary for individuals who have a myelodysplastic syndrome with a low or intermediate IPSS of 0-1.0 or an IPSS-R of 3.5 or less who have not responded to prior therapy.* 
   *Note: An IPSS is not required for the treatment of de novo or primary myelodysplastic syndrome or juvenile myelomonocytic leukemia (JMML) in the pediatric population.
3. Allogeneic (ablative and non-myeloablative) stem cell transplantation is considered medically necessary for individuals who have secondary myelodysplastic syndrome.
4. An allogeneic stem cell transplantation (ablative or non-myeloablative) after a prior autologous stem cell transplantation is considered medically necessary for individuals who meet the above criteria.
   Note: This applies if a previous autologous transplant was performed, regardless if the Position Statement deems autologous stem cell transplantation as investigational and not medically necessary.
5. A repeat allogeneic (ablative or non-myeloablative) stem cell transplantation due to primary graft failure or failure to engraft is considered medically necessary.

Investigational and Not Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered investigational and not medically necessary for individuals who do not meet the above criteria.
2. Autologous stem cell transplantation in individuals with CMML, MDS or myeloproliferative neoplasms is considered investigational and not medically necessary.
3. Allogeneic (ablative and non-myeloablative) stem cell transplantation is considered investigational and not medically necessary in individuals with the following myeloproliferative neoplasms (MPN: polycythemia vera, essential thrombocytopenia).
4. A second or repeat allogeneic (ablative or non-myeloablative) transplant due to persistent, progressive or relapsed disease is considered investigational and not medically necessary.
5. Hematopoietic stem cell harvesting for a future but unscheduled transplant is considered investigational and not medically necessary.

VI.  Myelofibrosis

Medically Necessary:

1. Allogeneic (ablative or non-myeloablative) stem cell transplantation is considered medically necessary in individuals with myelofibrosis.
2. An allogeneic stem cell transplantation (ablative or non-myeloablative) after a prior autologous stem cell transplantation is considered medically necessary.
   NOTE: This applies if a previous autologous transplant was performed, regardless if the Position Statement deems autologous stem cell transplantation as investigational and not medically necessary.
3. A repeat allogeneic (ablative or non-myeloablative) stem cell transplantation due to primary graft failure or failure to engraft is considered medically necessary.

Investigational and Not Medically Necessary:

1. Autologous stem cell transplantation in individuals with myelofibrosis is considered investigational and not medically necessary.
2. A second or repeat allogeneic (ablative or non-myeloablative) transplant due to persistent, progressive or relapsed disease is considered investigational and not medically necessary.
3. Hematopoietic stem cell harvesting for a future but unscheduled transplant is considered investigational and not medically necessary.