Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant

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.

Section: Discussionmentioning

confidence: 99%

Second allogeneic hematopoietic SCT for relapsed ALL in children

Kato

Hirono

Okamoto

et al. 2012

“…Therapeutic options are limited for those who relapse, as they tolerate further chemotherapy poorly, and repeat transplants have limited efficacy. 8,9 Immunotherapy offers a new approach to patients who relapse after allogeneic BMT. This has mostly been in the form of donor lymphocyte infusions (DLI), and several reports have demonstrated long-term survival with this approach.…”

mentioning

confidence: 99%

Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myelogenous leukemia

Kumar

Chen

Gastineau

et al. 2001

Summary:Allogeneic BMT is potentially curative for patients with acute myelogenous leukemia (AML) in first remission. However, many patients relapse after transplantation. Various immunotherapeutic options have been attempted with variable success in preventing relapse. Early identification of patients at high risk for relapse could allow prompt intervention. We examined the effect of slow lymphocyte recovery after siblingmatched allogeneic BMT on the risk of relapse in patients with AML. We also examined the effect of prednisone-containing GVHD prophylaxis on the rate of lymphocyte recovery. Patients with absolute lymphocyte count (ALC) Ͻ150 × 10 6 /l by day +30 had a 3.5-fold higher risk of relapse (P = 0.0088) and a lower overall survival (P = 0.0079) than patients with a higher ALC. We did not find correlation between lymphocyte count determined earlier in the post-transplantation course (day +21) and the risk of relapse. Patients receiving prednisone had a significantly lower ALC at day +30 than those who did not receive prednisone (289 vs 549 × 10 6 /l, P = 0.002). We conclude that a slow lymphocyte recovery after allogeneic BMT for AML is strongly predictive of subsequent relapse and that the type of GVHD prophylaxis should be considered when analyzing lymphocyte recovery. Bone Marrow Transplantation (2001) 28, 951-956. Keywords: allogeneic; bone marrow transplantation; cyclosporine; lymphocyte recovery; prophylaxis; relapse Allogeneic BMT offers the potential for cure in patients with acute myelogenous leukemia (AML). Several studies of allogeneic BMT have shown a benefit for patients in first remission with high-risk AML. [1][2][3][4][5] However, 10% to 40% of patients who have complete remission after allogeneic BMT for AML eventually relapse. Several factors, includ- ing FAB type, 6 associated karyotypic abnormalities, 7 stage of the disease, conditioning regimen used, 3,5 GVHD prophylaxis, 6 and development of acute and chronic GVHD, have been shown to influence the incidence of relapse after allogeneic BMT for AML. Therapeutic options are limited for those who relapse, as they tolerate further chemotherapy poorly, and repeat transplants have limited efficacy. 8,9 Immunotherapy offers a new approach to patients who relapse after allogeneic BMT. This has mostly been in the form of donor lymphocyte infusions (DLI), and several reports have demonstrated long-term survival with this approach. [10][11][12][13] These results have led to evaluation of its role in preventing relapse; however, DLI is also associated with a risk of severe GVHD. Other approaches for prevention of relapse have included the use of cytokines like interferon-alpha (IFN-␣) and interleukin-2 (IL-2) or rapid withdrawal of immunosuppression. Since only a quarter to a third of patients relapse after allogeneic BMT, a need exists for prognostic variables that can prospectively identify patients at risk for relapse and thereby help select appropriate patients for prophylactic immunotherapy.Slow recovery of the lymphocyte count after allog...

“…These results suggest that in blastic relapse of Ph + leukaemia after SCT, STI571 might be considered a frontline treatment, as both DLI and chemotherapy have limited efficacy, 11 and a second myeloablative SCT is associated with considerable therapyrelated risks. 12 However, additional donor stem cells may be needed, in view of the possible marrow aplasia that may accompany the therapeutic response. Finally, in all cases (patients 5-8) who relapsed after allogeneic SCT, donor chimerism was apparently totally lost at the time of commencement of STI571.…”

Section: Discussionmentioning

confidence: 99%

Tyrosine kinase inhibitor STI571 in the treatment of Philadelphia chromosome-positive leukaemia failing myeloablative stem cell transplantation

Lie

et al. 2002

Summary:Eight patients with Philadelphia chromosome-positive (Ph + ) leukaemia relapsing from stem cell transplantation (SCT) (one syngeneic and seven allogeneic) were treated with the tyrosine kinase inhibitor STI571. Five patients relapsing as chronic myeloid leukaemia (CML) in chronic phase achieved a complete haematological response, with complete and major cytogenetic responses occurring in four and one cases, respectively. One patient became negative for BCR/ABL in the bone marrow. Three patients relapsed as acute leukaemia (two CML in myeloblastic crisis and one Ph + acute lymphoblastic leukaemia), all of whom achieved haematological and cytogenetic responses. One patient also became BCR/ABL negative. However, pancytopenia and graft-versus-host disease led to cessation of treatment in the remaining two cases, which was followed by disease recurrence refractory to further STI treatment. Our results showed that Ph + leukaemic relapses after SCT might respond well to STI571 therapy.