|
MP 8.01.32 |
Hematopoietic Stem-cell Transplantation for Acute Lymphoblastic Leukemia |
|
Medical Policy |
|
|
|
Section |
Original Policy Date |
Last Review Status/Date |
|
Issue |
|
Disclaimer
Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.
Description
Hematopoietic Stem-Cell Transplantation
Hematopoietic stem-cell transplantation (SCT) 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 cytotoxic drugs, with or without whole-body radiation therapy. Bone-marrow stem cells may be obtained from the transplant recipient (i.e., autologous SCT) or from a donor (i.e., allogeneic SCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem cells in it are antigenically “naïve” and thus are associated with a lower incidence of rejection or graft-versus-host disease (GVHD). Cord blood is discussed in greater detail in policy No. 7.01.50.
Immunologic compatibility between infused stem cells and the recipient is not an issue in autologous SCT. However, immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allogeneic SCT. Compatibility is established by typing of 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.
Conventional Preparative Conditioning for Hematopoietic SCT
The conventional practice of allogeneic SCT involves administration of myelotoxic agents (e.g., cyclophosphamide, busulfan) with or without total-body irradiation at doses sufficient to cause bone marrow failure. The beneficial treatment effect in this procedure results from chemotherapeutic eradication of malignant cells with an associated immune-mediated graft-versus-malignancy effect. While such treatment may eliminate the malignant cells, patients are as likely to die from opportunistic infections, GVHD, and/or organ failure as from the underlying malignancy. In any allogeneic SCT, immune suppressant drugs are used to minimize graft rejection while allowing development of the graft-versus-leukemia effect.
Autologous SCT necessitates myeloablative chemotherapy to eradicate cancerous cells from the blood and bone marrow, thus permitting subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic progenitor cells. As a consequence, autologous SCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous SCT are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment, but not GVHD.
Reduced-Intensity Conditioning for Allogeneic SCT
Reduced-intensity conditioning (RIC) refers to chemotherapy regimens that seek to reduce adverse effects secondary to bone marrow toxicity, while retaining the beneficial graft-versus-malignancy effect of allogeneic transplantation. These regimens do not eradicate the patient’s hematopoietic ability, thereby allowing for relatively prompt hematopoietic recovery (e.g., 28 days or less) even without a transplant. Patients who undergo RIC with allogeneic SCT 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. A number of different cytotoxic regimens, with or without radiotherapy, may be used for RIC allotransplantation. They represent a continuum in their effects, from nearly totally myeloablative, to minimally myeloablative with lymphoablation.
Acute Lymphoblastic Leukemia (ALL)
Childhood ALL
ALL is the most common cancer diagnosed in children and represents almost 25% of cancers in children younger than 15 years. (1) Approximately 95% of children with ALL achieve remission with up to 85% long-term survival rates. Survival rates have improved with the identification of effective drugs and combination chemotherapy through large, randomized trials, integration of presymptomatic central nervous system prophylaxis, and intensification and risk-based stratification of treatment. (2)
ALL is a heterogeneous disease with different genetic alterations resulting in distinct biologic subtypes. Patients are stratified according to certain clinical and genetic risk factors that predict outcome, with risk-adapted therapy tailoring treatment based on the predicted risk of relapse. (3) Two of the most important factors predictive of risk are patient age and white blood cell count (WBC) at diagnosis. (3) Certain genetic characteristics of the leukemic cells strongly influence prognosis. Clinical and biologic factors predicting clinical outcome can be summarized as follows (2)
| FACTOR | FAVORABLE | UNFAVORABLE |
| Age at diagnosis | 1-9 years | <1 or >9 years |
| Sex | Female | |
| WBC count | <50,000/μL | ≥50,000/μL |
| Genotype |
Hyperdiploidy (>50 chromosomes) t(12;21) or TEL/AML1 fusion |
Hypodiploidy (<45 chromosomes) t(9:22) or BCR/ABL fusion t(4;11) or MLL/AF4 fusion |
| Immunophenotype | Coomon, preB | ProB, T-lineage |
Adult ALL
ALL accounts for approximately 20% of acute leukemias in adults. Approximately 60-80% of adults with ALL can be expected to achieve complete remission after induction therapy, however, only 35-40% can be expected to survive two years. (4) Differences in the frequency of genetic abnormalities that characterize adult ALL versus childhood ALL help, in part, to explain the outcome differences between the 2 groups. For example, the “good prognosis” genetic abnormalities like hyperdiploidy and t(12;21) are seen much less commonly in adult ALL, whereas they are some of the most common in childhood ALL. Conversely, “poor prognosis” genetic abnormalities like the Philadelphia chromosome (t(9;22)) are seen in 25-30% of adult ALL but infrequently in childhood ALL. Other adverse prognostic factors in adult ALL include age greater than 35 years, poor performance status, male sex, and leukocytosis at presentation of '>30,000/μL (B-cell lineage) and '>100,000/μL (T-cell lineage).
Policy
Children
Allogeneic or autologous hematopoietic stem-cell transplantation (SCT) may be considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) in first complete remission but at high risk of relapse. (For definition of high-risk factors, see Policy Guidelines.)
Autologous or allogeneic hematopoietic SCT may be considered medically necessary to treat childhood ALL in second or greater remission or refractory ALL.
Allogeneic hematopoietic SCT is considered investigational to treat relapsing ALL after a prior autologous SCT.
Adults
Autologous or allogeneic hematopoietic SCT may be considered medically necessary to treat adult ALL in first complete remission but at high risk of relapse (for definition of high-risk factors, see Policy Guidelines).
Allogeneic hematopoietic SCT may be considered medically necessary to treat adult ALL in second or greater remissions, or in patients with relapsed or refractory ALL.
Autologous hematopoietic SCT is investigational to treat adult ALL in second or greater remission or those with refractory disease.
Allogeneic hematopoietic SCT is investigational to treat relapsing ALL after a prior autologous SCT.
Reduced-intensity conditioning (RIC) allogeneic hematopoietic SCT may be considered medically necessary as a treatment of ALL in patients who are in complete marrow and extramedullary first or second remission, and who for medical reasons (see Policy Guidelines), would be unable to tolerate a standard myeloablative conditioning regimen.
NOTE: The use of donor leukocyte infusions to treat relapse after allogeneic SCT for either children or adults is considered separately in policy No. 2.03.03.
Policy Guidelines
Determining High-Risk of Relapse:
In childhood ALL, adverse prognostic factors include the following: age less than 1 year or more than 9 years, male gender, white blood cell count at presentation above 50,000/μL, hypodiploidy (<45 chromosomes), t(9:22) or BCR/ABL fusion, t(4;11) or MLL/AF4 fusion, and ProB or T-lineage immunophenotype. Several risk stratification schema exist, but, in general, the following findings help define children at high risk of relapse: 1) poor response to initial therapy including poor response to prednisone prophase defined as an absolute blast count of 1000/μL or greater, or poor treatment response to induction therapy at 6 weeks with high risk having ≥1% minimal residual disease measured by flow cytometry), 2) all children with T-cell phenotype and 3) patients with either the t(9;22) or t(4;11) are considered high risk regardless of early response measures.
In adult ALL, risk factors for relapse are less well defined, but an adult patient with any of the following may be considered at high risk for relapse: age greater than 35 years, leukocytosis at presentation of >30,000/μL (B-cell lineage) and >100,000/μL (T-cell lineage),“poor prognosis” genetic abnormalities like the Philadelphia chromosome (t(9;22)), extramedullary disease and time to attain complete remission longer than 4 weeks {American Society of Hematology Education Program Handbook, 2007).
Two general categories of patients are considered potential candidates for reduced-intensity conditioning (RIC) allotransplants: those who would otherwise be considered candidates for a conventional myeloablative allotransplant, and those who would not. In the first category, a RIC allotransplant could be considered as a variant of a standard chemotherapy conditioning regimen for patients in whom allotransplant therapy is already accepted. In the latter category, RIC would be considered for patients with malignancies that are effectively treated with conventional myeloablative allogeneic transplants but whose age (typically older than 55 years) or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status) preclude use of a standard myeloablative conditioning regimen.
In patients who qualify for a myeloablative allogeneic hematopoietic SCT on the basis of overall health and disease status, either a myeloablative or RIC allogeneic SCT may be considered medically necessary.
Benefit Application
BlueCard/National Account Issues
The following considerations may supersede this policy:
- State mandates requiring coverage for autologous bone marrow transplantation offered as part of clinical trials of autologous bone marrow transplantation approved by the National Institutes of Health (NIH).
- Some plans may participate in voluntary programs offering coverage for patients participating in NIH-approved clinical trials of cancer chemotherapies, including autologous bone marrow transplantation.
- Some contracts or certificates of coverage (e.g., FEP) may include specific conditions in which autologous bone marrow transplantation would be considered eligible for coverage.
Rationale
Childhood ALL
The policy on childhood acute lymphoblastic leukemia (ALL) was initially based on TEC Assessments completed in 1987 and 1990. (5,6) In childhood ALL, conventional chemotherapy is associated with complete remission rates of about 95%, with long-term durable remissions of 60%. Therefore, for patients in a first complete remission (CR1), stem-cell transplantation (SCT) therapy is considered necessary only in those with risk factors predictive of relapse (see Description section above).
The prognosis after first relapse is related to the length of the original remission. For example, leukemia-free survival is 40%–50% for children whose first remission was longer than 3 years, compared to only 10%–15% for those with early relapse. Thus, SCT may be a strong consideration in those with short remissions. At present, the comparative outcomes with either autologous or allogeneic SCT are unknown.
Three reports describing the results of randomized controlled trials (RCTs) that compared outcomes of hematopoietic SCT to outcomes with conventional-dose chemotherapy in children with ALL were identified subsequent to the TEC Assessment. (7-9) The children enrolled in the RCTs were being treated for high-risk ALL in CR1 or for relapsed ALL. These studies reported that overall outcomes after SCT were generally equivalent to overall outcomes after conventional-dose chemotherapy. While SCT administered in CR1 was associated with fewer relapses than conventional-dose chemotherapy, it was also associated with more frequent deaths in remission (i.e., from treatment-related toxicity). A more recently published randomized trial (PETHEMA ALL-93, n = 106) demonstrated no significant differences in disease-free survival or overall survival rates at median follow-up of 78 months in children with very high-risk ALL in CR1 who received allogeneic or autologous SCT versus standard chemotherapy with maintenance treatment (10). Similar results were observed using either intention-to-treat (ITT) or per-protocol (PP) analyses. However, the authors point out several study limitations that could have affected outcomes, including the relatively small numbers of patients; variations among centers in the preparative regimen used prior to SCT and time elapsed between CR and undertaking of assigned treatment; and the use of genetic randomization based on donor availability rather than true randomization for patients included in the allogeneic SCT arm.
These results, and reviews of other studies, (11,12) suggest that while overall and event-free survival are not different after SCT compared to conventional-dose chemotherapy, SCT remains an important therapeutic option in the management of childhood ALL, especially for patients considered at high risk of relapse. This conclusion is further supported by an evidence-based systematic review of the literature sponsored by the American Society for Blood and Marrow Transplantation (ASBMT) (13). Other investigators recommend that patients should be selected for this treatment using risk-directed strategies. (14)
Clinicaltrials.gov Database
A search of the Clinicaltrials.gov database in March 2007 identified 4 open or active Phase III and IV trials of hematopoietic SCT for childhood ALL as follows:
1. Phase II/III study of standard and novel conditioning therapy and allogeneic blood or marrow transplantation in patients with severe aplastic anemia or hematologic malignancy (RPCI-RP-9815);
2. Phase III randomized study of induction chemotherapy followed by consolidation and reinduction with or without late intensification followed by a maintenance regimen or allogeneic bone marrow transplantation in infants with acute lymphoblastic leukemia (ICU-INTERFANT99);
3. Phase III randomized study of filgrastim (G-CSF)-mobilized peripheral blood SCT versus bone marrow transplantation from HLA-compatible unrelated donors in patients with hematologic malignancies (BMTCTN-0201); and
4. Phase III randomized study of nonmyeloablative conditioning comprising low-dose total body irradiation with versus without fludarabine followed by HLA-matched related allogeneic hematopoietic SCT in patients with hematologic malignancies at low or moderate risk for graft rejection (FHCRC-1813.00).
Adult ALL
The policy on adult ALL was initially based in part on a 1997 TEC Assessment of autologous (not allogeneic) SCT. (15) This Assessment offered the following conclusions:
-
For patients in CR1, the data suggest survival is equivalent after autologous SCT or conventional-dose chemotherapy. For these patients, the decision between autologous SCT and conventional chemotherapy may reflect a choice between intensive therapy of short duration and longer but less-intensive treatment.
-
In other settings, such as in second (CR2) or subsequent remissions, data were inadequate to determine the relative effectiveness of autologous SCT compared to conventional chemotherapy.
An evidence-based systematic review sponsored by the American Society for Blood and Marrow Transplantation (ASBMT) addressed the issue of SCT in adults with ALL. (16) The ASBMT panel recommends hematopoietic SCT for adults with high-risk disease in CR1, but not for standard-risk patients. It also recommends SCT for patients in CR2, although data are not available to directly compare outcomes with alternatives.
Based on results from 3 randomized clinical trials the ASBMT panel concluded that allogeneic SCT is superior to autologous SCT in adult patients in CR1, although available data did not permit separate analyses in high-risk versus low-risk patients. (17-19) However, partially conflicting results were reported in a multicenter (35 Spanish hospitals) randomized trial (PETHEMA ALL-93; n =222) published after the ASBMT literature search. (20) Among 183 high-risk patients in CR1, those with an HLA-identical family donor were assigned to allogeneic SCT (n =84); the remaining cases were randomized to autologous SCT (n =50) or to delayed intensification followed by maintenance chemotherapy up to 2 years in CR (n =48). At median follow-up of 70 months, the study did not detect a statistically significant difference in outcomes between all 3 arms by both per-protocol and intention-to-treat analyses. However, the authors point out several study limitations that could have affected outcomes, including the relatively small numbers of patients; variations among centers in the preparative regimen used prior to SCT; differences in risk group assignment; and the use of genetic randomization based on donor availability rather than true randomization for patients included in the allogeneic SCT arm.
A phase III randomized study of allogeneic or autologous SCT versus conventional consolidation and maintenance chemotherapy is specific to patients with ALL in CR1 (ECOG 2993). (21) After induction treatment that included imatinib mesylate for Philadelphia chromosome-positive patients, Philadelphia chromosome-positive patients received autologous or allogeneic SCT followed by imatinib mesylate. Philadelphia chromosome-negative patients received either conventional consolidation/maintenance therapy or autologous SCT. The final results of this study suggest a significant benefit of allogeneic SCT over chemotherapy or autologous SCT in patients with Philadelphia chromosome-negative high-risk ALL. (21)
While allogeneic SCT may be an option for some adults with ALL, for several reasons allogeneic transplant remains controversial in the treatment of adults with ALL. First, the increased morbidity and mortality from GVHD limit its use, particularly for older patients. Second, evidence is scant for a beneficial graft-versus-leukemia effect in this disease to counterbalance the harms from GVHD. Finally, even for adults who survive the procedure, there is a significant relapse rate, and overall very few adults are long-term disease-free survivors. Taken together, current evidence supports the use of allogeneic SCT for the poor-risk subgroup of those with ALL in association with the Philadelphia chromosome or in patients with refractory or relapsed ALL.
Two other randomized controlled trials and 1 large registry-based retrospective review were published on SCT to treat ALL in adults. (22-24) These studies did not compare outcome after SCT to outcome after conventional-dose chemotherapy, but rather compared (a) outcome according to stem-cell source (bone marrow versus peripheral blood); (b) outcome using primed or unprimed peripheral blood stem cells; or (c) the benefits of adding interleukin-2 as post-transplant therapy. The results of these studies and several dozen uncontrolled clinical series confirm the existing policy on the use of autologous or allogeneic SCT to treat adult ALL in first or subsequent remission or in relapse (see above).
Clinicaltrials.gov Database
An updated search (March 2007) of Clinicaltrials.gov showed 4 active clinical trials on hematologic malignancies include adult ALL patients as follows:
-
Phase II/III study of standard and novel conditioning therapy and allogeneic blood or marrow transplantation in patients with severe aplastic anemia or hematologic malignancy (RPCI-RP-9815);
-
Phase III randomized study of filgrastim (G-CSF)-mobilized peripheral blood SCT versus bone marrow transplantation from HLA-compatible unrelated donors in patients with hematologic malignancies (BMTCTN-0201); and
-
Phase III randomized study of nonmyeloablative conditioning comprising low-dose total body irradiation with versus without fludarabine followed by HLA-matched related allogeneic hematopoietic SCT in patients with hematologic malignancies at low or moderate risk for graft rejection (FHCRC-1813.00).
-
Phase II/III protocol using busulfan, cyclophosphamide, and melphalan as conditioning therapy for patients receiving SCT for acute leukemia or myelodysplastic syndrome (MDS). It is hypothesized that this new regimen will be well tolerated and curative (0005M52481)
Allogeneic Transplant after Prior Failed Autologous Transplant
A 2000 TEC Assessment focused on allogeneic SCT after a prior failed autologous SCT, in the treatment of a variety of malignancies, including ALL. (25) The TEC Assessment found that data were inadequate to permit conclusions about outcomes of this treatment strategy. Published evidence was limited to small, uncontrolled clinical series with short follow-up. Updated literature searches have not identified any additional evidence to permit conclusions on this use of SCT.
National Comprehensive Cancer Network Guidelines
The National Comprehensive Cancer Network clinical practice guidelines for non-Hodgkin’s lymphoma indicate autologous or allogeneic SCT is appropriate for treatment of poor risk patients with lymphoblastic lymphoma (i.e., when disease is considered to be systemic). (26) These guidelines are generally consistent with this policy.
2008 Updates
The policy was updated with a literature search through May 2008 and again in October 2008.
Two studies were published on the use of RIC regimens for allogeneic SCT in patients with ALL. The first was a multicenter single-arm study of patients (n =43, median age 19 years; range: 1-55) in second complete remission (CR2). (27) The 3-year overall survival rate was 30%, with 100-day and treatment-related mortality rates of 15% and 21%, respectively. Despite achievement of complete donor chimerism in 100% of the patients, 28 (65%) had leukemic relapse, with 67% ultimately succumbing to their disease. In a registry-based study, 97 adult patients (median age 38 years, range 17-65) underwent RIC and allogeneic SCT to treat ALL in CR1 (n =28), beyond CR1 (CR2/CR3, n =26/5) and advanced or refractory disease (n =39). (28) With median follow-up of about 3 years, in the overall population 2-year OS was 31%, with non-relapse mortality of 28% and relapse rate of 51%. In patients transplanted in CR1, overall survival was 52%; in CR2/CR3, it was 27%; in patients with advanced or refractory ALL, overall survival was 20%. These data suggest RIC and allogeneic SCT have some efficacy as salvage therapy in high-risk ALL.
Thus, based on currently available data and clinical input as noted in the following section, RIC allogeneic SCT may be considered medically necessary in patients who demonstrate complete marrow and extramedullary first or second remission, could be expected to benefit from a myeloablative allogeneic SCT, and who, for medical reasons, would be unable to tolerate a myeloablative conditioning regimen. Additional data are necessary to determine whether some patients with ALL and residual disease may benefit from RIC allogeneic SCT.
Physician Specialty Society and Academic Medical Center Input
In response to requests, input was received from one Physician Specialty Society (two reviewers) and 2 Academic Medical Centers while this policy was under review. While the various Physician Specialty Societies and Academic Medical Centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the Physician Specialty Societies or Academic Medical Centers, unless otherwise noted. There was strong consensus among reviewers that RIC allogeneic SCT was of value in patients who were in complete remission. With this exception, there was general support for the policy statements.
2008 National Comprehensive Cancer Network Guidelines
The National Comprehensive Cancer Network clinical practice guidelines (v.3.2008) remain generally consistent with this policy. (26)
2008 National Cancer Institute Clinical Trials Database (PDQ®)
A search of the NCI PDQ database in May 2008 identified 5 active phase III trials that involve stem-cell support for patients with ALL (adult or pediatric). Information on these trials can be accessed via the following link (http://www.cancer.gov/search/psrv.aspx?cid=113933&protocolsearchid=4634244 ).
References:
- Physician Data Query (PDQ®). Childhood acute lymphoblastic leukemia. Modified 09/05/2008. Available online at http://www.cancer.gov/cancertopics/pdq/treatment/childALL/healthprofessional.
- Pieters R, Carroll WL. Biology and treatment of acute lymphoblastic leukemia. Pediatr Clin N Am 2008; 55(1):1-20.
- Carroll WL, Bhojwani D, Min DJ et al. Pediatric acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2003:102-31.
- Physician Data Query (PDQ®). Adult acute lymphoblastic leukemia treatment. Modified 09/25/2008. Available online at http://www.cancer.gov/cancertopics/pdq/treatment/adultALL/healthprofessional.
- 1990 TEC Evaluations; p. 254.
- 1987 TEC Evaluations; p. 243.
- Wheeler KA, Richards SM, Bailey CC et al. Bone marrow transplantation versus chemotherapy in the treatment of very high-risk childhood acute lymphoblastic leukemia in first remission: results from Medical Research Council UKALL X and XI. Blood 2000; 96(7):2412-8.
- Harrison G, Richards S, Lawson S et al. Comparison of allogeneic transplant versus chemotherapy for relapsed childhood acute lymphoblastic leukaemia in the MRC UKALL R1 trial. Ann Oncol 2000; 11(8):999-1006.
- Lawson SE, Harrison G, Richards S et al. The UK experience in treating relapsed childhood acute lmphoblastic leukaeima: a report on the Medical Research Council UK ALLR1 study. Br J Haematol 2000; 108(3):531-43.
- Ribera JM, Ortega JJ, Oriol A et al. Comparison of intensive chemotherapy, allogeneic, or autologous stem-cell transplantation as postremission treatment for children with very high risk acute lymphoblastic leukemia: PETHEMA ALL-93 trial. J Clin Oncol 2007; 25(1):16-24.
- Uderzo C. Indications and role of allogeneic bone marrow transplantation in childhood very high risk acute lymphoblastic leukemia in first complete remission. Haematologica 2000; 85(11 suppl):9-11.
- Uderzo C, Dini G, Locatelli F et al. Treatment of childhood acute lymphoblastic leukemia after the first relapse: curative strategies. Haematologica 2000; 85(11 suppl):47-53.
- Hahn T, Wall D, Camitta B et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in children: an evidence-based review. Biol Blood Marrow Transplant 2005; 11(11):823-61.
- Gaynon PS, Trigg ME, Heerema NA et al. Children’s Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995. Leukemia 2000; 14(12):2223-33.
- 1997 TEC Assessments; Tab 25.
- Hahn T, Wall D, Camitta B et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. Biol Blood Marrow Transplant 2006; 12(1):1-30.
- Dombret H, Gabert J, Boiron JM et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia–results of the prospective multicenter LALA-94 trial. Blood 2002; 100(7):2357-66.
- Hunault M, Harousseau JL, Delain M et al. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood 2004; 104(10):3028-37.
- Attal M, Blaise D, Marit G et al. Consolidation treatment of adult acute lymphoblastic leukemia: a prospective, randomized trial comparing allogeneic versus autologous bone marrow transplantation and testing the impact of recombinant interleukin- 2 after autologous bone marrow transplantation. BGMT Group. Blood 1995; 86(4):1619-28.
- Ribera JM, Oriol A, Bethencourt C et al. Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial. Haematologica 2005; 90(10):1346-56.
- Goldstone AH, Richards SM, Lazarus HM et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 2008; 111(4):1827-33.
- Blaise D, Kuentz M, Fortanier C et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early stage leukemia: a report from the Société Française de Greffe de Moelle. J Clin Oncol 2000; 18(3):537-46.
- Blaise D, Attal M, Reiffers J et al. Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission. Eur Cytokine Netw 2000; 11(1):91-8.
- Champlin RE, Schmitz N, Horowitz MM et al. Blood stem cells compared to bone marrow as a source of hematopoietic cells for allogeneic transplantation. Blood 2000; 95(12):3702-9.
- 2000 TEC Assessments; Tab 9.
- Non-Hodgkin’s Lymphoma. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology.v.3.2008; http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf.
- Gutierrez-Aguirre CH, Gomez-Almaguer D, Cantu-Rodriguez OG et al. Non-myeloablative stem cell transplantation in patients with relapsed acute lymphoblastic leukemia: results of a multicenter study. Bone Marrow Transplant 2007; 40(6):535-9.
- Mohty M, Labopin M, Tabrizzi R et al. Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Haematologica 2008; 93(2):303-6.
|
Codes |
Number |
Description |
|
CPT |
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 |
Thawing of previously frozen harvest |
|
|
38209 |
Washing of harvest |
|
|
38210 |
Specific cell depletion with harvest, T cell depletion |
|
|
38211 |
Specific cell depletion with harvest, T 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 |
Bone marrow; aspiration only |
|
|
38221 |
Bone marrow; biopsy, needle or trocar |
|
|
38230 |
Bone marrow harvesting for transplantation |
|
|
38240 |
Bone marrow or blood-derived peripheral stem-cell transplantation: allogeneic |
|
|
38241 |
Same as 38240 but autologous |
|
|
86812, 86813, 86816, 86817, 86821, 86822 |
Histocompatibility studies code range (e.g., for allogeneic transplant) |
|
|
86915 |
Bone marrow, modification or treatment to eliminate cells (i.e., purging) |
|
ICD-9 Procedure |
41.00 |
Bone marrow transplant, not otherwise specified |
|
|
41.01 |
Autologous bone marrow transplant |
|
|
41.02 |
Allogeneic bone marrow transplant with purging |
|
|
41.03 |
Allogeneic bone marrow transplant without purging |
|
|
41.04 |
Autologous hematopoietic stem-cell transplant |
|
|
41.05 |
Allogeneic hematopoietic stem-cell transplant |
|
|
41.06 |
Cord blood stem-cell transplant |
|
|
41.07 |
Autologous hematopoietic stem-cell transplant with purging |
|
|
41.08 |
Allogeneic hematopoietic stem-cell transplant with purging |
|
|
41.09 |
Autologous bone marrow transplant with purging |
|
|
41.91 |
Aspiration of bone marrow from donor for transplant |
|
|
99.79 |
Other therapeutic apheresis (includes harvest of stem cells) |
|
ICD-9 Diagnosis |
204.00 – 204.01 |
Acute lymphoblastic leukemia code range |
|
HCPCS |
Q0083, Q0084, Q0085 |
Chemotherapy administration code range |
|
|
J9000, J9001, J9010, J9015, J9017, J9020, J9025, J9027, J9031, J9035, J9040, J9041, J9045, J9050, J9055, J9060, J9062, J9065, J9070, J9080, J9090, J9091, J9092, J9093, J9094, J9095, J9096, J9097, J9098, J9100, J9110, J9120, J9130, J9140, J9150, J9151, J9160, J9165, J9170, J9175, J9178, J9181, J9182, J9185, J9190, J9200, J9201, J9202, J9206, J9208, J9209, J9211, J9212, J9213, J9214, J9215, J9216, J9217, J9218, J9219, J9225, J9226, J9230, J9245, J9250, J9260, J9261, J9263, J9264, J9265, J9266, J9268, J9270, J9280, J9290, J9291, J9293, J9300, J9303, J9305, J9310, J9320, J9340, J9350, J9355, J9357, J9360, J9370, J9375, J9380, J9395, J9600, J9999 |
Chemotherapy drugs code range |
|
|
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) |
|
Type of Service |
Therapy |
|
|
Place of Service |
Inpatient/Outpatient |
|
Index
Acute Lymphoblastic Leukemia, High-dose Chemotherapy
Acute Lymphocytic Leukemia, High-dose Chemotherapy
ALL, High-dose Chemotherapy
High-dose Chemotherapy, Acute Lymphocytic Leukemia
Stem-Cell Transplant, Acute Lymphocytic Leukemia (ALL)
Policy History
|
Date |
Action |
Reason |
|
04/30/00 |
Add to Therapy section |
New policy; policy based on original master policy on high-dose chemotherapy for ALL. However, policy statement is unchanged |
|
08/18/00 |
Replace policy |
Policy statement revised to state that allogeneic transplant after a prior failed autotransplant is considered investigational, based on 2000 TEC Assessment |
|
12/18/02 |
Replace policy |
Literature review update through November 2002. Policy updated with expanded rationale and new references; policy statement unchanged. Updated CPT codes |
|
11/9/04 |
Replace policy |
Literature review update through August 2004. Added update on clinical trials and NCCN guidelines; policy statement unchanged |
|
09/27/05 |
Replace policy |
Literature review update through August 2005. NCI clinical trials and NCCN guidelines information unchanged. No clinical trials publications to change previous conclusions; policy statement unchanged |
|
04/17/07 |
Replace policy |
Literature review update through March 2007. NCI clinical trials updated; NCCN guidelines information unchanged. Reference numbers 6, 9, 12-17 added; policy statement unchanged |
| 06/12/08 | Replace policy | Literature review update through May 2008. NCI clinical trials updated; NCCN guidelines information unchanged. Reference numbers 23 and 24 added; policy statement unchanged |
| 12/11/08 | Replace policy | Policy revised with literature search, reference numbers 1 to 4 added, other references renumbered. Reference 21 updated. Clinical input reviewed. New policy statement added that RIC allogeneic SCT may be considered medically necessary in select patients in complete remission. Policy title changed to state “Acute Lymphoblastic Leukemia.” |
Find a Provider
Medicare
Prescription Drugs
Medicare Formulary