No abstract

Summary. We prospectively investigated minimal residual disease (MRD) in 51 children with B-lineage acute lymphoblastic leukaemia (ALL) treated according to the Fralle 93 protocol. PCR follow-up was performed in children in morphological and cytogenetic complete remission, provided an immunoglobulin (IgH) gene rearrangement could be detected using FR3/J H amplimers. MRD was studied according to our previously described methodology, with a few modifications including the use of a consensus J H probe to control for PCR efficiency variations.Out of the initial 51 patients, 34 were assessable for MRD at the end of induction at the time of analysis. MRD levels were as follows: >1/10 3 in 26%, 1/10 3 to 1/10 4 in 50% and <1/10 4 or not detectable in 24%. With a median follow-up of 20 months there were five relapses, all of which occurred in the group of patients with MRD >1/10 3 . To date, none of the patients with MRD р1/10 3 (good molecular responder) has relapsed. Classification according to molecular response at the end of induction did not correlate with the conventional risks groups: there were no statistically significant differences between good and bad molecular responders. Of particular interest is the absence of correlation between WBC at diagnosis and MRD level at the end of induction. We conclude that classification of patients into good and bad molecular responders using PCR seems to be a better prognostic indicator than conventional risk factors in childhood B-lineage ALL. Patients with MRD level >1/10 3 have a particularly poor outcome and should always be considered for alternative therapeutic strategies in the future, whereas in good molecular responders belonging to poor or intermediate risk categories, treatment de-escalation might be contemplated.

The effectiveness of granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) in the treatment of febrile neutropenic cancer patients remains controversial. To assess their role in this condition, we conducted a systematic review of randomised trials published as full papers. A methodological evaluation using a specifically designed quality scale was performed before meta-analysis. Eleven trials were eligible, 8 of which were meta-analysable. The median quality score for the 11 pooled trials was 58.3% (range: 33.3%-68.8%). No significant quality difference was observed between positive (colony-stimulating factor more effective) and negative trials ( P=0.36). No quality difference was observed between the 8 meta-analysable studies and the 3 others, with respective median scores of 59.3% and 50%. No advantage was detected for the use of CSF in terms of mortality from febrile neutropenia, with a relative risk of 0.71 (95% CI 0.44-1.15). The relative risk was 0.66 (95% CI 0.39-1.13) in the G-CSF subgroup and 0.97 (95% CI 0.34-2.79) in the GM-CSF subgroup. Aggregation of the results on infection-related mortality, length of stay in hospital, fever and of neutropenia duration, antibiotic therapy adaptation and duration, superinfection rate and toxicity was not possible owing to the lack of adequate data in the publications. On the basis of this review, we cannot recommend the routine use of G-CSF or GM-CSF in established febrile neutropenia.

No abstract

Autologous transplantation using peripheral blood stem cells (PBSCs) collected after chemotherapy, followed by growth factor administration (ASCT), is increasingly used in the treatment of non‐Hodgkin's lymphoma (NHL). However, quantitative data regarding contaminating malignant cells in the harvests are still scarce. We prospectively investigated 37 diffuse large‐cell lymphomas (DLCLs) in complete remission (CR) that were treated according to multicentric protocols at our centre. DNA was extracted from the diagnostic lymph node. The complementarity‐determining region (CDR) III was sequenced and a patient‐specific oligomer synthesized. Contamination was evaluated semiquantitatively by polymerase chain reaction (PCR) and was confirmed by a limiting dilution analysis. PBSCs collected at regeneration after administration of granulocyte colony‐stimulating factor (G‐CSF), steady‐state bone marrow (BM) and peripheral blood samples at CR were compared. DNA was available in 37 patients, from which 22 rearrangements could be sequenced. Patients (n = 15) who had both the required follow‐up samples and a suitable clonal marker were investigated. In two cases, the patient‐specific PCR assay set up at diagnosis later gave false‐negative results in samples in which clonal DNA was still detectable by other sets of primers. PBSC contamination was highly variable: 7 out of 15 patients showed a PBSC/BM ratio of NHL cells greater than 1 log, whereas 8 out of 15 patients showed no difference and could vary from one apheresis to another. Eight ASCTs were performed, five of which used highly contaminated PBSCs: four patients relapsed early, three with disseminated lymphoma. Thus, 50% of DLCLs in CR seem to mobilize significantly malignant cells at regeneration under G‐CSF. Considering the higher numbers of cells reinfused, this translates into a much higher number of lymphoma cells reinfused when compared with autologous bone marrow transplantation (ABMT). However, their clonogenic potential remains unknown and, despite concerning observations in certain cases, it is still unclear whether this has an impact upon the outcome of ASCT.