Severe ototoxicity following carboplatin-containing conditioning regimen for autologous marrow transplantation for neuroblastoma.

Children with neuroblastoma receiving high-dose carboplatin as part of their conditioning regimen for autologous marrow transplantation have a high incidence of speech frequency hearing loss. We evaluated hearing loss in 11 children with advanced stage neuroblastoma who underwent autologous marrow transplantation, following a conditioning regimen containing high-dose carboplatin (2g/m2, total dose). Audiometric evaluations were obtained at diagnosis, prior to and following transplant. Exposure to other known ototoxins also was assessed. All patients sustained worsening of hearing following high-dose carboplatin. Nine of the 11 children (82%) had evidence of speech frequency hearing loss post transplant for which hearing aids were recommended (grades 3-4). Three of the nine children had speech frequency loss prior to transplant which progressed following transplant. The entire group was heavily pre-treated with platinum-containing chemotherapy pre-BMT and had extensive exposure to other ototoxins, including aminoglycoside antibiotics, diuretics, and noise exposure - all of which could have exacerbated the effects of carboplatin. High-dose carboplatin is ototoxic, particularly in patients who have been primed with previous platinum therapy or other ototoxic agents. We conclude that further efforts are needed to monitor and minimize this complication. In cases where hearing loss is inevitable due to cumulative ototoxic exposures, families need to be adequately prepared for the tradeoffs of potentially curable therapy.

Relapsed acute lymphoblastic leukemia: similar outcomes for autologous and allogeneic marrow transplantation in selected children.

The therapy of choice for relapsed childhood acute lymphoblastic leukemia is controversial. We retrospectively compared the outcome of 57 patients who received autologous bone marrow transplantation (BMT) with 17 patients who underwent allogeneic BMT for B cell lineage acute lymphoblastic leukemia after at least one marrow relapse. The allogeneic BMT cohort included only those who would also have been eligible for autologous BMT had they not had a matched sibling donor. Specifically, patients who were not in complete remission, those with T cell positive leukemia, t(9;22) or those with only an extramedullary relapse were excluded from both groups. Conditioning regimens included total body irradiation and chemotherapy. Age, white blood count at diagnosis, and duration of first and longest complete remissions were comparable for the two groups. The median follow-up of the event-free survivors was 4.8 years for those who received an autologous BMT (n = 26) and 4.6 years for those who received an allogeneic BMT (n = 8). The relapse rate was higher in the autologous BMT group and the incidence of non-leukemic deaths higher in the allogeneic BMT group. Event-free survival at 3 years was comparable for the two groups (47% +/- 7 vs 53% +/- 12, autologous vs allogeneic, respectively; P = 0.77). Based upon these findings, we concluded that the outcome for autologous BMT was equivalent to allogeneic BMT for relapsed childhood B cell lineage acute lymphoblastic leukemia in selected clinical situations.

Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections.

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN AND METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage--colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU-GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G-CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.