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.
Summary.Intensive chemotherapy produces a lower complete remission (CR) rate in the myelodysplastic syndromes (MDS) than in de novo acute myeloid leukaemia (AML), possibly due in part to a higher incidence of P glycoprotein (PGP) expression in MDS blast cells. We designed a randomized trial of intensive chemotherapy with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged р 65 years with high-risk MDS. Patients were randomized to receive mitoxantrone 12 mg/m 2 /d days 2-5 þ AraC 1 g/m 2 /12 h days 1-5, with (Q þ ) or without (Q ¹ ) quinine (30 mg/kg/d). 131 patients were included. PGP expression analysis was successful in 91 patients. In the 42 PGP-positive cases, 13/ 25 (52%) patients in the Q þ group achieved CR, compared to 3/17 (18%) patients in the Q ¹ group (P ¼ 0·02) and median Kaplan-Meier survival was 13 months in the Q þ group, and 8 months in the Q ¹ group (P ¼ 0·01). No life-threatening toxicity was observed with quinine. In conclusion, the results of this randomized study show that quinine increases the CR rate and survival in PGP-positive MDS cases treated with intensive chemotherapy.
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