A French Cohort of Childhood Leukemia Survivors: Impact of Hematopoietic Stem Cell Transplantation on Health Status and Quality of Life

AbstractThe late effects and quality of life (QoL) in childhood acute leukemia survivors were compared between hematopoietic stem cell transplantation (HSCT) recipients and patients who underwent conventional therapy. The study included 943 patients, 256 of whom underwent HSCT (27.1%). Medical visits were conducted to detect the occurrence of physical late effects. Based on patient age, different questionnaires were used to assess QoL. To evaluate the association between HSCT and each type of late effect or QoL dimension, the appropriate multivariate regressions were performed. QoL mean scores were compared with those obtained for age- and sex-matched French control subjects. Of all the survivors, 674 (71.5%) had at least 1 late effect, with the risk being 5.0 CI95 (3.0-8.6) times higher for transplantation survivors. For child survivors, scoring of QoL showed no significant differences between the treatment groups. The adult HSCT survivors reported lower physical dimension QoL scores than chemotherapy survivors. Compared with French norms, the survivor group reported a significantly lower mental composite score; however, the physical composite score showed no significant difference. Thus, transplanted survivors have a high risk of developing late effects, resulting in a decreased physical well-being in adulthood. However, long after treatment completion, childhood leukemia survivors report that effects on psychological well-being are more important than they are in physical QoL dimensions

Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent ten-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted in chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and DLI (n=30), or isolated reinfusion of donor lymphocytes (DLI) (n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy = 385 d, second allograft = 391d, chemotherapy = 174d, DLI alone = 140d, palliative care = 43d. A second SCT or a combination of chemotherapy and donor lymphocytes infusion yielded similar outcome (HR=0.85, p=0.53) unlike chemotherapy alone (HR 1.43 p=0.04), palliative care (HR=4.24, p<0.0001) or isolated DLI (HR=1,94, p<0.04). Despite limitations in this retrospective setting, strategies including immunointervention appear superior to other approaches, mostly in AML

Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg(®)) in children with relapsed/refractory myeloid leukemia

BACKGROUND: Gemtuzumab ozogamicin (GO) is a cytotoxic anti-CD33 monoclonal antibody that has given promising preliminary results in adult myeloid CD33+ AML. We conducted a retrospective multicenter study of 12 children treated with GO on a compassionate basis (median age 5.5 y). Three patients (2 MDS/AML, 1 JMML) were refractory to first-line treatment, 8 patients with de novo AML were in refractory first relapse, and one patient with de novo AML was in 2(nd )relapse after stem cell transplantation (SCT). CD33 expression exceeded 20% in all cases. METHODS: GO was administered alone, at a unit dose of 3–9 mg/m(2), once (3 patients), twice (3 patients), three (5 patients) or five times (1 patient). Mean follow-up was 128 days (8–585 d). RESULTS: There were three complete responses (25%) leading to further curative treatment (SCT). Treatment failed in the other nine patients, and only one patient was alive at the end of follow-up. NCI-CTC grade III/IV adverse events comprised hematological toxicity (n = 12), hypertransaminasemia (n = 2), allergy and hyperbilirubinemia (1 case each). There was only one major adverse event (grade IV allergy). No case of sinusoidal obstruction syndrome occurred. CONCLUSION: These results warrant a prospective trial of GO in a larger population of children with AML