Second transplant for acute and chronic leukemia relapsing after first HLA-identical sibling transplant

Eapen, Mary; Giralt, Sergío; Horowitz, Mary M.; Klein, John P.; Wagner, John E.; Zhang, M. J.; Tallman, Martin S.; Marks, David I.; Camitta, Bruce M.; Champlin, Richard E.; Ringdén, Olle; Bredeson, Christopher; Martino, Rodrigo; Rp, Gale; Cairo, Mitchell S.; Litzow, Mark R.; Lima, Marcos de

doi:10.1038/sj.bmt.1704645

Cited by 202 publications

(289 citation statements)

References 27 publications

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“…This result confirms our earlier report based on less mature data from a diverse patient population treated similarly. 3 Furthermore, it resembles data from more recent series incorporating less intensive conditioning protocols, 6 but appears slightly better than the TRM with myeloablative regimens, either TBI-based or BUCY. 5,7,8 Early disease control was very satisfactory with 50/53 evaluable patients achieving CR at 1 month.…”

Section: Discussionmentioning

confidence: 86%

“…At 3 years our patients' relapse incidence was 56% and the OS rate 18%, similar to the results of some series, 8,22 but worse than the 40-50% relapse rate and 30% OS rate observed by other investigators after myeloablative or RIC. [5][6][7]23 A higher relapse incidence has been noted with the use of RIC regimens in some studies, 6 but there are exceptions. 23 Other possible causes for our series' high relapse rate are our patients' advanced median age, 6 early relapse p12 months after first allo-SCT in 32/58 patients, 7 and the fact that only 4/58 patients were transplantated in CR.…”

Section: Discussionmentioning

confidence: 99%

“…These patients pose a special therapeutic challenge, since they are especially prone to TRM due to heavy pretreatment, while also carrying a very high risk of relapse. [5][6][7][8] We tried to address both problems by developing a novel RIC protocol with fludarabine and thiotepa aiming to combine efficacy with low organ toxicity. 3 Thiotepa was chosen because it is a welltolerated alkylator with potent antileukaemic as well as stem-cell toxic activity, [17][18][19] whereas fludarabine is as immunosuppressive as CY, but less toxic and enhances alkylator-induced damage by inhibiting DNA repair.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Second, despite high TRM and GVHD rates, relapse remains the main cause of death in this very high-risk patient population. [5][6][7][8] The concept of allo-SCT with reduced-intensity conditioning (RIC) is based on the notion that the GVL contributes significantly to the curative potential. This permits dose reductions of preparative chemotherapy or radiation with a lower overall toxicity.…”

Section: Introductionmentioning

confidence: 99%

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Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML

Christopoulos

Schmoor

Waterhouse

et al. 2013

Bone Marrow Transplant

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A second allograft was offered to 58 relapsed AML patients after conditioning with fludarabine 90-150 mg/m 2 and thiotepa 15 mg/kg, in most cases with active disease. Median age was 53 years (range 23-69), median time to relapse after the first allo-SCT was 326 (47-2189) days and median follow-up was 6.7 years. GVHD prophylaxis consisted mainly of CsA and alemtuzumab. Response rates at 1 month were CR in 50 and persistent disease in 3/53 evaluable patients. At 3 years, the relapse incidence (95% confidence interval) was 56 (45-71)%, the TRM 31 (21-46)%, the OS rate was 18 (9-29)% and the EFS rate was 13 (5-23)%. OS improved with younger patient age, longer relapse-free interval after the first allo-SCT and the development of chronic GVHD. Patients p65 years old who relapsed 412 months after the first allograft (n ¼ 20) had a 3-year OS rate of 41 (19-62)%. Conventional cytogenetics and FLT3 mutation status did not affect outcome. Our regimen is feasible and provides at least for a subgroup of patients with AML recurrence after allo-SCT a reasonable therapeutic option in an otherwise fatal situation. Further modifications and a better understanding of the underlying biology could help lower the risk of relapse. INTRODUCTIONFor patients with AML, relapsing after allo-SCT prognosis is very poor. A second allograft is currently the only therapeutic approach capable of inducing long-term remissions in patients who cannot be salvaged with DLI. 1,2 This approach has, however, two main limitations. First, many of these patients cannot tolerate a second allo-SCT because of accumulated organ toxicities and opportunistic infections, which increase the risk for TRM and severe GVHD. 3,4 Second, despite high TRM and GVHD rates, relapse remains the main cause of death in this very high-risk patient population. [5][6][7][8] The concept of allo-SCT with reduced-intensity conditioning (RIC) is based on the notion that the GVL contributes significantly to the curative potential. This permits dose reductions of preparative chemotherapy or radiation with a lower overall toxicity. 9 In 2008, we reported the results of a phase II RIC trial using fludarabine 5 Â 30 mg/m 2 and thiotepa 3 Â 5 mg/kg in patients with recurrent or persistent haematological malignancies after a previous auto-or allo-SCT. 3 In this series, a TRM (95% confidence interval) of 29 (14-44)% at 2 years despite heavy pretreatment demonstrated the feasibility of our regimen, but the low number of patients in each diagnostic subgroup and the relatively short follow-up precluded a thorough evaluation of efficacy.Here we analyse the long-term outcome of a larger, homogeneous patient cohort with AML at relapse after first allo-SCT treated in a similar manner.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML

Christopoulos

Schmoor

Waterhouse

et al. 2013

Bone Marrow Transplant

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“…There are no confirmatory data about an advantage for the selection of a different donor for the second SCT, although there are some reports 4 about this selection, including a study showing that different donor has a trend toward better survival. 12 Our analysis did not provide evidence supporting the use of a different donor.…”

mentioning

confidence: 93%

Second allogeneic hematopoietic SCT for relapsed ALL in children

Kato

Hirono

Okamoto

et al. 2012

Bone Marrow Transplant

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A second SCT is generally accepted as the only potentially curative approach for ALL patients that relapse after SCT, but the role of second SCT for pediatric ALL is not fully understood. We performed a retrospective analysis of 171 pediatric patients who received a second allo-SCT for relapsed ALL after allo-SCT. OS at 2 years was 29.4 ± 3.7%, the cumulative incidence of relapse was 44.1±4.0% and non-relapse mortality was 18.8±3.5%. Relapse occurred faster after the second SCT than after the first SCT (117 days vs 164 days, P ¼ 0.04). Younger age (9 years or less), late relapse (180 days or more after first SCT), CR at the second SCT, and myeloablative conditioning were found to be related to longer survival. Neither acute GVHD nor the type of donor influenced the outcome of second SCT. Multivariate analysis showed that younger age and late relapse were associated with better outcomes. Our analysis suggests that second SCT for relapsed pediatric ALL is an appropriate treatment option for patients that have achieved CR, which is associated with late relapse after the first SCT. Keywords: second transplantation; relapse; ALL; children INTRODUCTION SCT is the most effective treatment for high-risk and refractory leukemia, but relapse is still a major event of allo-SCT. It is generally accepted that a second SCT is the only potentially curative approach for patients who relapse after allo-SCT, but only some patients are eligible for a second SCT because of the high mortality and morbidity associated with repeated allo-SCT. In addition, high relapse rates occur because of the resistance of leukemic cells that have not been eliminated by the first SCT. Some previous studies have examined the role of second SCT, 1 --10 but because of the small number of patients in these studies, the efficacy and safety of second allo-SCT for pediatric ALL patients that have relapsed after SCT remains unclear.In this study, to investigate the prognostic factors of second SCT and identify subgroups for whom second SCT is effective, we performed a retrospective analysis of 171 patients who received a second SCT for relapsed ALL after allo-SCT.

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Relapse of Hematologic Malignancy After Allogeneic Hematopoietic Transplantation

Champlin¹

2015

Thomas’ Hematopoietic Cell Transplantation

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Second transplant for acute and chronic leukemia relapsing after first HLA-identical sibling transplant

Cited by 202 publications

References 27 publications

Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML

Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML

Second allogeneic hematopoietic SCT for relapsed ALL in children

Relapse of Hematologic Malignancy After Allogeneic Hematopoietic Transplantation

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