Transplant Outcomes by Disease and Disease Stage

Appropriate timing of hematopoietic cell transplantation is critical to favorable outcomes. With some exceptions, transplanting earlier in the disease course generally leads to better outcomes.

On this page is comprehensive, disease-specific information on optimal transplant timing for both allogeneic transplants (related and unrelated) and autologous transplants.

 

Acute lymphoblastic leukemia (ALL)

Clinical studies and data collected by the Center for International Blood and Marrow Transplant Research (CIBMTR) have shown higher survival rates for adult ALL patients and pediatric patients with an HLA-identical sibling donor when allogeneic transplantation is performed earlier in the disease course (Figures 1, 2). [1,2,3] The survival advantage of allogeneic transplant in first complete remission (CR1) is clear for adult patients with Ph+ ALL or other high-risk factors. [1,2,4]

Figure 1.
Probability of Survival after HLA-Identical Sibling Transplants for ALL, Age <20 Years, 1998-2006 - by disease status. (CIBMTR data)


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Figure 2.
Probability of Survival after HLA-Identical Sibling Transplants for ALL, Age >20 Years, 1998-2006 - by disease status. (CIBMTR data)


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For patients with standard-risk ALL in CR1, the latest data show that matched sibling allogeneic transplant, rather than autologous transplant or chemotherapy, is the most effective treatment. A large, ongoing, prospective trial (UKALL 12/ECOG 2993) comparing allogeneic transplant to continuing chemotherapy or autologous transplant at CR1 for adult patients is showing significantly improved overall survival after allogeneic transplant for standard-risk patients.

This study of more than 1,980 patients showed that patients experienced significantly higher five-year OS and event-free survival (EFS) (63% and 59%, respectively) than patients who received either autologous transplants or chemotherapy (51% and 48%, respectively). [2] Data from this same large-scale study has demonstrated that achieving CR with induction therapy significantly improves long-term survival in adult patients with ALL. [5]

For patients receiving unrelated donor transplants, NMDP data show that for adult patients, five-year survival is significantly increased in patients transplanted in CR1 compared to patients in CR2 or with advanced disease (log-rank p-value < 0.0001) (Figure 3).

Figure 3.
ALL: Survival of adult marrow transplant patients, unrelated donor transplants facilitated by the NMDP, 1998-2006. (NMDP data)


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Five-year survival for pediatric patients is significantly increased for patients in CR1 (45%) and CR2 (21%) compared to patients with advanced disease (7%) (log-rank p-value < 0.0001) (Figure 4).

Figure 4.
ALL: Survival of pediatric marrow transplant patients, unrelated donor transplants facilitated by the NMDP, 1998-2006. (NMDP data)


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See further explanation of Figures 3 and 4 with downloadable PowerPoint^® slides.

A study of 260 adult ALL patients in CR1 found similar outcomes for autologous transplantation (n=101) and unrelated donor transplantation (n=159). This study used data sets from the National Marrow Donor Program (NMDP) (unrelated donor transplants) and the CIBMTR (autologous transplants).

Relapse was higher in autologous transplants, and one-year treatment-related mortality was higher in unrelated donor transplants. However, five-year leukemia-free survival in CR1 patients was similar for autologous transplantation (37%) and unrelated donor transplantation (39%). A non-significant trend was found favoring unrelated donor transplantation for patients in CR2. [6]

For recommendations from the NMDP and the American Society for Blood and Marrow Transplantation (ASBMT) on when to refer a patient with ALL for transplant consultation, see the Recommended Timing for Transplant Consultation. In addition, an independent panel of ALL experts convened by the ASBMT has developed a consensus document on the treatment of pediatric and adult ALL. The panel critically evaluated the evidence regarding the role of hematopoietic cell transplantation (autologous and allogeneic) and chemotherapy in treating patients with ALL. These recommendations have been published in Biology of Blood and Marrow Transplantation. [7,8]

Acute myelogenous leukemia (AML)

Allogeneic transplant following myeloablative cytotoxic therapy is currently considered the most effective antileukemic treatment option for adults with AML in remission. For patients with high-risk AML, most centers plan allogeneic transplants at an early phase in the treatment plan because of the patients' high risk of early relapse. [9] For adults receiving unrelated donor transplants, NMDP data show survival is significantly increased for transplants in CR1 or CR2 compared to transplants for patients with advanced disease (log-rank p-value < 0.0001) (Figure 8). For patients with an HLA-identical sibling donor, CIBMTR data show that the highest survival is obtained for allogeneic transplant in early disease stage (Figure 7).

However, for patients with favorable-risk AML in CR1, the risk of transplant-related mortality may not be justified, and chemotherapy or autologous transplant may be preferred. Autologous transplant is also more commonly used in older patients, who may be less able to tolerate the allogeneic transplant regimen, and in patients without a matched donor. Autologous transplants lead to better outcomes when performed earlier in the disease stage (Figures 5 and 6).

A 2006 study comparing 668 autologous and 476 unrelated donor transplants in patients with AML in 1st or 2nd CR found that while autologous and unrelated donor transplantation can each produce extended leukemia-free survival, the high transplant-related mortality (TRM) in unrelated donor transplantation offsets its superior anti-leukemia effect.

In this study of transplants reported to the CIBMTR, TRM was significantly higher after unrelated donor transplantation, although relapse was lower. In patients transplanted in 1st CR, three-year survival was 57% (autologous patients) and 44% (unrelated donor) (p=0.002). In patients transplanted in 2nd CR, three-year survival was 46% (autologous) and 33% (unrelated donor) (p=0.006). The authors noted, however, that cytogenetics were known in only two-thirds of patients and that therefore any effects of treatment bias are unknown. [10]

Whether autologous transplant or chemotherapy is more effective has not been conclusively determined, as studies have produced differing results. [9]

For AML patients with high-risk cytogenetics, an allogeneic transplant early in CR1 has been shown, in some studies, to give a clear advantage. A trial that studied 734 patients on an intent-to-treat basis (the EORTC/GIMEMAAML-10 trial) found that for patients with bad/very bad risk cytogenetics, the 4-year disease-free survival (DFS) of patients with a donor (assigned to allogeneic transplant) was 43.4%, but only 18.4% for patients without a donor (assigned to autologous transplant). However, the DFS values for patients with good/intermediate risk cytogenetics were similar for both groups. [11]

In a 2007 study of 261 AML patients undergoing matched unrelated donor transplantation, cytogenetic risk factors had no effect on five-year overall survival and DFS for patients in first complete remission. In second complete remission, there was a non-significant trend toward better survival for patients with favorable cytogenetics. The researchers concluded that matched unrelated donor transplantation should be considered for patients with unfavorable cytogenetics lacking a suitable HLA-matched sibling donor. [12]

A panel of experts convened by the ASBMT have developed treatment recommendations for pediatric AML patients, which were published in 2007. [13] These recommendations include:

• Autologous transplantation and chemotherapy have equivalent outcomes in CR1
• Allogeneic transplantation has superior survival than chemotherapy and is recommended in CR1
• Matched related donor transplantation has superior survival than autologous transplantation in CR1
• Matched related donor transplantation is preferred in CR1 or CR2
• If a matched related donor is not available, alternative donors could be considered in CR2

For pediatric patients with an unrelated donor, NMDP data show five-year survival is significantly increased for patients transplanted in CR2 compared to CR1 or advanced disease (log-rank p-value < 0.0001) (Figure 9). However, a greater percent of patients transplanted in CR1 had poor-risk cytogenetics compared to patients transplanted in CR2. Unrelated transplant for AML in CR1 is indicated if the patient has poor-risk cytogenetics at diagnosis or induction failure. See the Recommended Timing for Transplant Consultation for recommendations for both adult and pediatric patients.

Figure 5.
Probability of Survival after Autotransplants for AML, Age <20 Years, 1998-2006 - by disease status. (CIBMTR data)


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Figure 6.
Probability of Survival after Autotransplants for AML, Age >20 Years, 1998-2006 - by disease status. (CIBMTR data)


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Figure 7.
Probability of Survival after HLA-Identical Sibling Transplants for AML with Myeloablative Conditioning, 1998-2006 - by disease status. (CIBMTR data)


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Figure 8.
AML: Survival of adult marrow transplant patients, unrelated donor transplants facilitated by the NMDP by disease stage, 1998-2006. (NMDP data)


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Figure 9.
AML: Survival of pediatric marrow transplant patients, unrelated donor transplants facilitated by the NMDP by disease stage, 1998-2006. (NMDP data)


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See further explanation of Figures 8 and 9 with downloadable PowerPoint^® slides.

Chronic myelogenous leukemia (CML)

Although allogeneic transplant is the only potential cure for CML, the effectiveness of imatinib mesylate for many patients with CML has made treatment decisions more complex. Resistance to imatinib -- most commonly through a Bcr-Abl mutation, although amplifications and point mutations are also possible -- is approximately 4% per year in patients receiving the drug in early chronic phase, with higher rates for patients in advanced stages. For this reason, allogeneic transplantation remains an important salvage option for patients who develop imatinib resistance. [14]

For CML patients treated with allogeneic transplant, studies and CIBMTR data prior to use of imatinib have shown that patients' likelihood of survival is significantly better when transplants are performed within one year of diagnosis (Figure 10). [15,16]

NMDP data for patients with unrelated donors show five-year survival is significantly increased in patients transplanted in first chronic phase compared to patients transplanted in accelerated or second chronic phase or blastic phase (log-rank p-value < 0.0001) (Figure 11). However, the benefits of early transplant must be weighed against potential transplant-related complications and the potential benefits of imatinib therapy.

Imatinib produces high response rates in patients with chronic phase CML. In one study of 1106 patients, at 18 months, patients treated with imatinib showed an estimated rate of complete cytogenetic response of 76.2% compared to 14.5% for those treated with interferon-alfa plus cytarabine, the previously common non-transplant treatment. [17]

For nearly all patients, front-line treatment with imatinib followed by assessment of cytogenetic response every 3 to 6 months will determine if and when transplant is indicated. Patients recommended to proceed to transplant include those resistant to or with an incomplete cytogenetic response to imatinib. [18,19] See the Recommended Timing for Transplant Consultation for details.

The graft-versus-leukemia effect is particularly pronounced in CML. [20] Reduced-intensity conditioning followed by allogeneic transplantation may be an acceptable treatment for some CML patients. A 2005 study of 186 patients (median age 50 years) transplanted for CML using a reduced-intensity conditioning regimen reported a three-year overall survival of 58% and a progression-free survival of 37%. [21]

Figure 10.
Probability of Survival after Transplants for CML in Chronic Phase, 1998-2006 - by donor type and disease duration. (CIBMTR data)


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Figure 11.
CML: Survival of adult marrow transplant patients by disease stage, unrelated donor transplants facilitated by the NMDP by disease stage, 1998-2006. (NMDP data)


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See further explanation of Figure 11 with downloadable PowerPoint^® slides.

Myelodysplastic syndromes (MDS)

Disease-free survival after allogeneic hematopoietic cell transplant for MDS is correlated with patient age, MDS subtype, prognostic score and chromosomal abnormalities. [22] CIBMTR data for patients with HLA-identical sibling donors show a higher likelihood of survival for transplants for patients transplanted in early disease stages for both related and unrelated donors (Figures 12 and 13).

However, for patients with unrelated donors, NMDP data show no significant 5-year survival advantage for RA/RARS subtypes compared to RAEB/RAEB-T subtypes (Figure 14), nor is there a significant difference in the survival of marrow and PBSC transplants for adults with MDS - RAEB/RAEB-T by conditioning regimen (Figure 15). Note that these data do not use International Prognostic Scoring System (IPSS) scores that correlate blast percentage, cytogenetics and number of lineages affected by cytopenia at diagnosis with outcome.

Although several studies have shown better patient outcomes when allogeneic transplants are performed soon after diagnosis and at an early stage of disease, [22,23,24] an accurate assessment of a patient's prognosis using the IPSS criteria is important to determining the timing for transplantation. [25,26] In a decision analysis based on HLA-identical sibling donor transplants performed 1990-99 and registered with the CIBTMR or performed at the Fred Hutchinson Cancer Research Center, Cutler, et al. [27] found the following:

• For patients with low and intermediate-1 risk IPSS scores, a higher life expectancy was associated with transplant that was delayed but performed prior to development of AML. This was true particularly for adult patients younger than 40.
• For patients with intermediate-2 and high-risk IPSS scores, a higher life expectancy was associated with transplant performed at diagnosis.

For recommendations from the NMDP and the ASBMT on when to refer a patient with MDS (scored using IPSS criteria) for transplant consultation, see the Recommended Timing for Transplant Consultation.

Figure 12.
Probability of Survival after Allotransplants for MDS, Age <20 years, 1998-2006, by disease status and donor type. (CIBMTR data)


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Figure 13.
Probability of Survival after Allotransplants for MDS, Age >20 Years, 1998-2006, by disease status and donor type. (CIBMTR data)


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Figure 14.
MDS: Survival of adult marrow transplant patients by FAB type, unrelated donor transplants facilitated by the NMDP, 1998-2006. (NMDP data)


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See further explanation of Figure 14 with downloadable PowerPoint^® slides.

Figure 15.
MDS - RAEB/RAEB-T: Survival of adult marrow and PBSC transplant patients by conditioning regimen, unrelated donor transplants facilitated by the NMDP, 1998-2006. (NMDP data)

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Multiple myeloma

Autologous transplantation is currently the standard of care for multiple myeloma and is recommended by the ASBMT as de novo therapy for patients who require treatment for multiple myeloma. [28] Although timing of autologous transplant does not have a significant impact on overall survival outcomes for patients with multiple myeloma, [29,30,31, and Figure 16] transplant as initial treatment is preferred because it may prolong time in remission and avoid the risk of myelodysplasia from conventional alkylating agent therapy. [28]

Although autologous transplantation lengthens survival, nearly all patients face eventual disease progression and relapse. One approach to address this is tandem autologous transplants, which in recent studies have shown better results than a single procedure. [32,33] Another approach that has shown promise is autologous transplant followed by non-myeloablative allogeneic transplant. [34] These two approaches are currently being studied in a large phase III multi-center trial by the BMT CTN. [35]

There has been renewed interest in allogeneic transplantation in multiple myeloma patients due to the development of reduced-intensity or non-myeloablative conditioning and the concurrent reduction in immediate transplant-related mortality. A multi-center study published in 2005 of 229 patients (median age 52 years) undergoing non-myeloablative allogeneic transplantation for multiple myeloma found a three-year overall survival of 41% and a progression-free survival of 21%. Adverse survival in this study was associated with chemoresistant disease and more than one prior transplant. The researchers concluded that although a graft-versus-myeloma effect is apparent and that non-myeloablative transplantation is feasible in multiple myeloma, “heavily pretreated patients and patients with progressive disease do not benefit.” [36]

Figure 16.
Probability of Survival after Hematopoietic Stem Cell Transplants for Multiple Myeloma, 1998-2006 - by donor type. (CIBMTR data)


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Non-Hodgkin's lymphoma (NHL)

For patients with diffuse large cell lymphoma or follicular lymphoma, data from the CIBMTR (Figures 17 and 18) show that autologous hematopoietic cell transplant outcomes are better in patients with chemotherapy-sensitive disease. However, patients' individual risk factors determine the recommended time for transplant; for many patients, transplant is considered at relapse (for details see the Recommended Timing for Transplant Consultation).

For diffuse large B-cell NHL, autologous transplantation is currently the standard of care. [37] The role of allogeneic transplant for NHL is under evaluation. Data from the CIBMTR for transplants using HLA-identical sibling donors show better outcomes in patients transplanted with chemotherapy-sensitive disease (Figures 19 and 20). Most patients with unrelated donors are transplanted at disease recurrence. Graft source (marrow or PBSC) has no significant impact on unrelated donor outcomes when using non-myeloablative preparative conditioning regimens (Figure 21).

Reviews of transplants for lymphomas reported to European and American registries from 1985-1998 have showed that relapse rates were better following allogeneic transplant for NHL. Nevertheless, because of high transplant-related mortality associated with allogeneic transplant, the overall survival was higher after autologous transplants. [38,39] However, the rates of allogeneic transplant-related mortality have continued to improve since the period covered in these reviews, and studies to evaluate the potential of allogeneic transplant in NHL treatment are ongoing.

Figure 17.
Probability of Survival after Autotransplants for Diffuse Large B-Cell Lymphoma, 2000-2006, by disease status. (CIBMTR data)


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Figure 18.
Probability of Survival after Autotransplants for Follicular Lymphoma, 2000-2006, by disease status. (CIBMTR data)


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Figure 19.
Probability of Survival after HLA-Identical Sibling Allotransplants for Follicular Lymphoma, 1998-2006, by disease status and conditioning regimen. (CIBMTR data)


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Figure 20.
Probability of Survival after HLA-Identical Sibling Allotransplants for Diffuse Large Cell Lymphoma, 1998-2006, by disease status and conditioning regimen. (CIBMTR data)


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Figure 21.
NHL: Survival of adult marrow non-myeloablative transplant patients, unrelated donor transplants facilitated by the NMDP by cell source, 1998-2006. (NMDP data)


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See further explanation of Figure 21 with downloadable PowerPoint^® slides.

Hodgkin's disease

The use of high-dose therapy with autologous hematopoietic cell transplant is considered a standard therapy for patients with chemosensitive relapsed and primary refractory Hodgkin's disease. [40] Studies have shown that active disease at the time of transplant and the number of previous chemotherapy treatments both have a significant influence on survival after transplant. [41,42]

Data from the CIBMTR also show the probability of survival after autologous transplant is better when it is performed during complete remission than during non-remission (Figure 22). Transplantation for patients who respond to therapy may therefore be considered early in the course of the disease, before the development of chemotherapy resistance and cumulative organ toxicity. [41,42] (See the Recommended Timing for Transplant Consultation.)

The use of allogeneic transplantation in treating Hodgkin's disease remains controversial. In one study of the EBMT registry of patients receiving transplants for lymphomas, Hodgkin's disease was the only lymphoma where relapse-free survival was poorer after allogeneic transplant than after autologous transplant. [38] However, a smaller study of 157 patients with relapsed or refractory Hodgkin's disease transplanted at Johns Hopkins Oncology Center between 1985 and 1998 found signs of a graft-versus-Hodgkin's disease effect and a lower risk of secondary AML/MDS following allogeneic transplant compared to autologous transplant, and recommended further study. [43]

Figure 22.
Probability of Survival after Autotransplants for Hodgkin Disease, 1998-2006, by disease status. (CIBMTR data)


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Other diseases

The following five curves show survival data from the NMDP and the CIBMTR of other diseases for which hematopoietic cell transplantation can be a curative therapy.

Fanconi anemia

Figure 23.
Fanconi Anemia: Overall Survival of Pediatric Patients (Age < 18 Years), unrelated donor reduced-intensity transplants facilitated by the NMDP, 1998-2006. (NMDP data)


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Severe aplastic anemia

Figure 24.
Severe Aplastic Anemia: Overall Survival of Adult (Age > 18 Years) and Pediatric (Age < 18 Years) Patients, unrelated donor marrow transplants facilitated by the NMDP, 1998-2006. (NMDP data)


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Figure 25.
Probability of Survival after Allotransplants for Severe Aplastic Anemia, 1998-2006 - by donor type and age. (CIBMTR data)


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Inherited immune system disorders

Figure 26.
Inherited Immune System Disorders: Overall Survival of Patients with Severe Combined Immunodeficiency (SCID) and Wiskott-Aldrich Syndrome (WAS), unrelated donor marrow transplants facilitated by the NMDP, 1998-2006. (NMDP data)


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Inherited metabolic disorders

Figure 27.
Inherited Metabolic Disorders: Overall Survival of Pediatric (Age < 18 Years) Patients with adrenoleukodystrophy (ALD)/metachromatic leukodystrophy (MLD) or Hurler syndrome, unrelated donor transplants facilitated by the NMDP, 1998-2006. (NMDP data)


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References

Acute lymphoblastic leukemia

1. Kiehl MG, Kraut L, Schwerdtfeger R, et al. Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: No difference in related compared with unrelated transplant in first complete remission. J Clin Oncol. 2004; 22(14):2816-2825.
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2. Rowe JM, Buck G, Fielding A, et al. In adults with standard-risk acute lymphoblastic leukemia (ALL) the greatest benefit is achieved from an allogeneic transplant in first complete remission (CR) and an autologous transplant is less effective than conventional consolidation/maintenance chemotherapy: Final results of the international ALL trial (MRC UKALL XII/ECOG E2993) [abstract]. Blood 2006; 108(11): abstract 2.
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3. Weisdorf D, Bishop M, Dharan B, et al. Autologous versus allogeneic unrelated donor transplantation for acute lymphoblastic leukemia: comparative toxicity and outcomes. Biol Blood Marrow Transplant. 2002; 8(4):213-220.
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4. 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):3028-3037.
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5. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005;106(12):3760-3767.
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6. Bishop MR, Logan BR, Gandham S, et al. Long-term outcomes of adults with acute lymphoblastic leukemia after autologous or unrelated donor bone marrow transplantation: a comparative analysis by the National Marrow Donor Program and Center for International Blood and Marrow Transplant Research. Bone Marrow Transplant. 2007; 41(7):635-642.
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7. 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):823-861.
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8. 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.
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Acute myelogenous leukemia

9. Löwenberg B, Griffin JD, Tallman MS. Acute myeloid leukemia and acute promyelocytic leukemia. Hematology 2003: American Society of Hematology Education Program Book. 82-101.
10. Lazarus HM, Pérez WS, Klein JP, et al. Autotransplantation versus HLA-matched unrelated donor transplantation for acute myeloid leukaemia: a retrospective analysis from the Center for International Blood and Marrow Transplant Research. Br J Haematol. 2006; 132(6):755-769.
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11. Willemze R, Suciu S, Mandelli F, de Witte T, Amador S. Autologous versus allogeneic stem cell transplantation in acute myeloid leukemia. Ann Hematol. 2004; 83(Suppl 1):S134.
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12. Tallman MS, Dewald GW, Gandham S, et al. Impact of cytogenetics on outcome of matched unrelated donor hematopoietic stem cell transplantation for acute myeloid leukemia in first or second complete remission. Blood. 2007; 110(1):409-417.
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13. Oliansky DM, Rizzo JD, Aplan PD, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in children: an evidence-based review. Biol Blood Marrow Transplant. 2007;13(1):1-25.
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Chronic myelogenous leukemia

14. Jabbour E, Jorge Cortes, Hagop M. Kantarjian, et al. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation–related imatinib failure. Blood. 2006; 108(4):1421-1423.
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15. Weisdorf DJ, Anasetti C, Antin JH, et al. Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor. Blood. 2002; 99(6):1971-1977.
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16. Davies SM, DeFor TE, McGlave PB, et al. Equivalent outcomes in patients with chronic myelogenous leukemia after early transplantation of phenotypically matched bone marrow from related or unrelated donors. Am J Med. 2001; 110(5):339-346.
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17. O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003; 348(11):994-1004.
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18. Melo JV, Hughes TP, Apperley JF. Chronic Myeloid Leukemia. Hematology 2003: American Society of Hematology Education Program Book. 132-152.
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19. Maziarz RT, Mauro MJ. Mini Review: Transplantation for chronic myelogenous leukemia: yes, no, maybe so … an Oregon perspective. Bone Marrow Transplant. 2003; 32(5):459-469.
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20. Guglielmi C, Arcese W, Dazzi F, et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood. 2002; 100(2):397-405.
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21. Crawley C, Szydlo R, Lalancette M, et al. Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT. Blood. 2005; 106(9):2969-2976.
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Myelodysplastic syndromes

22. Castro-Malaspina H, Harris RE, Gajewski J, et al. Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood. 2002; 99(6):1943-1951.
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23. Al-Ali HK, Brand R, van Biezen A, et al. A retrospective comparison of autologous and unrelated donor hematopoietic cell transplantation in myelodysplastic syndrome and secondary acute myeloid leukemia: a report on behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Leukemia. 2007; 21(9):1945-1951.
    http://www.nature.com/leu/journal/v21/n9/abs/2404774a.html
24. Oran B, Giralt S, Saliba R, et al. Allogeneic hematopoietic stem cell transplantation for the treatment of high-risk acute myelogenous leukemia and myelodysplastic syndrome using reduced-intensity conditioning with fludarabine and melphalan. Biol Blood Marrow Transplant. 2007; 13(4):454-462.
    http://www.bbmt.org/article/PIIS1083879106007798/abstract
25. Deeg HJ, Appelbaum FR. Hemopoietic stem cell transplantation for myelodysplastic syndrome. Curr Opin Oncol. 2000; 12(2):116-120.
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27. Cutler CS, Lee SJ, Greenberg P, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood, 2004; 104(2):579-585.
    http://www.bloodjournal.org/cgi/content/full/104/2/579

Multiple myeloma

28. Position Statement of the American Society for Blood and Marrow Transplantation. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of multiple myeloma. 2003.
    http://www.asbmt.org/policystat/policy.html
29. Hahn T, Wingard JR, Anderson KC, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of multiple myeloma: An evidence-based review. Biol Blood Marrow Transplant, 2003; 9(1):4-37.
    http://www.bbmt.org/article/PIIS1083879102000058/fulltext
30. Bladé J, Vesole GH, Gertz M. Transplantation for multiple myeloma: who, when, how often? Blood. 2003; 102(10):3469-3477.
    http://www.bloodjournal.org/cgi/content/full/102/10/3469
31. Fermand JP, Ravaud P, Chevret S, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998; 92(9):3131-3136.
    http://www.bloodjournal.org/cgi/content/full/92/9/3131
32. Attal M, Harousseau J-L, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003; 349(26):2495-2502.
    http://content.nejm.org/cgi/content/abstract/349/26/2495
33. Cavo M, Cellini C, Zamagni E, et al. Superiority of double over single autologous stem cell transplantation as first-line therapy for multiple myeloma [abstract]. Blood. 2004; 104(11): abstract 536.
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