Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Française de Greffe de Moelle (SFGM)

Abstract

Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T‐cell‐depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft‐vs.‐host disease (GVHD) grade II and 38% chronic GVHD. The 5‐year overall and disease‐free survival were 32 ± 8% and 30 ± 8%, respectively, with a risk of relapse of 44 ± 12% and a transplant‐related mortality of 45 ± 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA‐identical donor was female and who relapsed more than 1 year after the first transplant.

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

“…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. Nevertheless, as in other series, most patients subsequently relapsed and died from their leukaemia.…”

“…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.…”

“…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.…”

“…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.…”

Double allogeneic hematopoietic SCT as a rescue therapy for poor-risk hematological malignancies

“…Several approaches have been evaluated in the past: (1) reduction of the Double HSCT for hematological malignancies G Stussi et al immunosuppression, 23 (2) donor lymphocyte infusions with or without previous reinduction chemotherapy, 32 (3) second single allogeneic HSCT 6,8,[33][34][35][36][37] and (4) dHSCT. 10,14 However, only a small percentage of relapsed patients are well enough for intensive treatment.…”