Search

Between January 1989 and November 1995, 259 patients with multiple myeloma (MM), 22 stage I, 57 stage II and 180 stage III at diagnosis were treated with myeloablative high-dose therapy followed by autologous peripheral blood stem cell (PBSC) transplantation. The median time from diagnosis to transplantation was 17 months (6–112). At the time of transplant, 56 patients were in CR, 153 in PR, 25 were nonresponders and 25 had progressive disease. Mobilization of stem cells was performed with G-CSF alone in 141 cases, chemotherapy plus G-CSF in 65, chemotherapy plus GM-CSF in 36 and chemotherapy alone in 17 patients. The conditioning regimen consisted of high-dose melphalan alone in 96 patients, melphalan plus TBI in 73, busulfan plus melphalan in 56, busulfan plus cyclophosphamide in 27 and cyclophosphamide plus TBI in seven. The median durations of neutropenia (>0.5 × 109/l) and thrombocytopenia (>20 × 109/l) were 12 (5–118) and 13 days (5–360), respectively. Transplant-related mortality occurred in 11 patients (4%). Once a stable graft was achieved, 114 patients (44%) received maintenance treatment with recombinant alpha interferon (IFN-α). Among the 248 patients evaluable for response 125 (51%) had a CR and 100 had a PR (40%). The median duration of progression-free survival (PFS) and overall survival (OS) after transplantation was 23 and 35 months, respectively. Univariate analysis showed that response status pretransplant, only one line of primary induction treatment and IFN-αmaintenance treatment post-transplant significantly influenced OS. Female sex, pretransplant responsive disease, and treatment with IFN-α post-transplant were the factors significantly influencing PFS. The conditioning regimen and method of stem cell mobilization had no significant impact on OS and PFS. On multivariate analysis the only independent factors associated with a longer survival were the number of... [ABSTRACT FROM AUTHOR]

Summary:In the present study, we analyze the efficacy of prophylaxis with meropenem in patients receiving a matched related donor allogeneic transplant. In total, 38 patients were sequentially treated with meropenem starting on the day of the first febrile episode (n=17, group A) vs prophylactic meropenem starting on the first day with <500/mm3 granulocytes (n=21, group B), and maintained until resolution of fever or after granulocyte count >500/mm3. Of these, 16 (94%) patients in group A developed fever as compared to 16 (76%) in group B (P=0.02). While only one patient in group A did not require first-line antibiotherapy, there were seven (33%) in group B who did not require it (P=0.01) since fever lasted less than 72?h. In addition, 52% patients in group B did not require second-line antibiotics as compared to 11% among patients in group A (P=0.04). In multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02); P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04-0.62); P=0.04) significantly influenced the development of fever. In conclusion, the current pilot study suggests that the use of prophylaxis with meropenem during the period of neutropenia in patients undergoing allogeneic transplantation favorably affects the morbidity of the procedure by reducing febrile episodes.Bone Marrow Transplantation (2004) 33, 183-187. doi:10.1038/sj.bmt.1704335 Published online 1 December 2003 [ABSTRACT FROM AUTHOR]

We have performed a prospective study to evaluate early chimerism and its kinetics after allogeneic peripheral blood stem cell transplantation among 68 patients who received a reduced-intensity conditioning (RIC) regimen with fludarabine plus melphalan (n=40) or busulphan (n=28). Chimerism was analyzed by polymerase chain reaction amplification of short tandem repeats in unfractionated (UF) and/or fractionated nucleated cells from bone marrow and peripheral blood (PB). All of the patients showed initial donor engraftment and no patient presented primary or secondary graft failure. In UF samples, the probability of achieving stable complete donor chimerism (CDC) in PB within the first 6 months was 70% on day +30, 85% on day +100 and 95% on day +180. CDC in granulocytes was observed in nearly all cases from day +30 onwards. CDC in T cells, however, differed among melphalan and busulphan recipients during the first 3 months (100 vs 0% on day +30 and 93 vs 20% on day +90, respectively). In multivariate analysis, the only significant variable associated with the achievement of early CDC was having received more than two lines of chemotherapy pretransplant (P<0.02). No correlation was found between the rate of achieving early CDC and the occurrence of acute graft-versus-host disease (GVHD) or disease progression post-transplant. In multivariate analysis, the only variable that influenced the incidence of disease progression post-transplant was the development of chronic extensive GVHD (P<0.05). In conclusion, a state of CDC is readily obtained within the first 6 months after our RIC protocols. Donor myeloid engraftment occurs rapidly in all cases, while early T-cell CDC is more common in more immunosuppressed hosts and, perhaps, in melphalan recipients.Bone Marrow Transplantation (2003) 31, 387-392. doi:10.1038/sj.bmt.1703846 [ABSTRACT FROM AUTHOR]

Presents a study that examined the association between standard allogeneic stem cell transplantation (SCT) and high transplant-related mortality (TRM) in patients who have failed a prior autologous SCT (ASCT) in Spain. Effects of reduced-intensity conditioning (RIC) on myeloablative transplants; List of diseases treated with ASCT, including leukemia; Percentage of transplant-related mortality; Main cause of treatment failure; Analysis of the development of RIC.

Contaminating tumour cells in apheresis products have proved to influence the outcome of patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (APBSCT). The gene scanning of clonally rearranged VDJ segments of the heavy chain immunoglobulin gene (VDJH) is a reproducible and easy to perform technique that can be optimised for clinical laboratories. We used it to analyse the aphereses of 27 MM patients undergoing APBSCT with clonally detectable VDJH segments, and 14 of them yielded monoclonal peaks in at least one apheresis product. The presence of positive results was not related to any pre-transplant characteristics, except the age at diagnosis (lower in patients with negative products, P = 0.04). Moreover, a better pre-transplant response trended to associate with a negative result (P = 0.069). Patients with clonally free products were more likely to obtain a better response to transplant (complete remission, 54% vs 28%; >90% reduction in the M-component, 93% vs 43% P = 0.028). In addition, patients transplanted with polyclonal products had longer progression-free survival, (39 vs 19 months, P = 0.037) and overall survival (81% vs 28% at 5 years, P = 0.045) than those transplanted with monoclonal apheresis. In summary, the gene scanning of apheresis products is a useful and clinically relevant technique in MM transplanted patients. Bone Marrow Transplantation (2001) 28, 665–672. [ABSTRACT FROM AUTHOR]

We compared the occurrence of severe infections following 71 reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplants (PBSCT) and 123 standard myeloablative PBSCT (MINI and STAND groups, respectively) from HLA-identical siblings. The probability of 1-year infection-related mortality (IRM) was 19% in the STAND group and 10% in the MINI group (log-rank, P = 0.3). On multivariate analysis the only significant variable associated with a higher risk of IRM was the development of moderate-to-severe GVHD (P = 0.005). The probability of developing CMV infection was 39% in the STAND group and 21% in the MINI group (P = 0.03) (43% and 21%, respectively, in seropositive donor/recipient pairs, P = 0.01), and the probability of developing CMV disease was 9.5% and 1%, respectively (P = 0.05) (11% and 1%, respectively, in seropositive donor/recipient pairs, P = 0.03). Multivariate analysis of CMV infection identified four variables associated with a higher risk: CMV positive serostatus (P = 0.05), STAND transplant group (P = 0.02), the development of moderate-to-severe GVHD (P < 0.001) and a dose of CD34+ cells infused below 6 × 106/kg (P = 0.01). Invasive fungal infections and pneumonias of unknown origin did not differ between groups, and neither did other severe non-CMV viral infections and bacterial infections. Our results suggest that RIC allogeneic PBSCT may decrease the risk of dying from an opportunistic infection and reduces the occurrence of CMV infection and disease. Overall, the development of GVHD (acute or chronic) is an important risk factor for these complications. Other infections continue to pose a significant threat to recipients of RIC allografts, stressing that prophylactic and supportive measures are an important aspect in their care. Bone Marrow Transplantation (2001) 28, 341–347. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effect of alpha-IFN maintenance treatment after autologous stem cell transplantation (ASCT) for multiple myeloma in a retrospective registry analysis. 473 patients with multiple myeloma who received IFN maintenance treatment ASCT were compared with 419 patients who did not receive IFN-treatment. Patients who were evaluable for response and in complete or partial remission at 6 months after ASCT were eligible, after excluding patients with graft failure. Cox proportional hazards assumptions were checked and handled by stratification. The prognostic variables unevenly distributed between the two groups were statistically corrected for in the Cox analysis. 391 patients reached complete remission (CR) after ASCT (203 in the IFN group and 188 in the no-IFN group) and 501 were in partial remission (PR, IFN 270, no-IFN 231). Overall survival (OS) and progression-free survival (PFS) were significantly better in the IFN-group (OS, 78 vs 47 months, P = 0.007, and PFS, 29 vs 20 months, P = 0.006, respectively). The difference in OS and PFS was most strongly pronounced in the PR patients. 209 patients have died (IFN, 84; no-IFN, 125). Progressive myeloma was the cause of death in 94% of the IFN-treated patients and in 83% of the no-IFN group (P = NS). Thus, IFN maintenance treatment after ASCT was associated with better OS and PFS. Treatment seemed to be most beneficial in patients who did not achieve CR. The difference in median survival was as long as 2.5 years, and although part of this difference is attributable to differences in other prognostic factors, it might justify possible differences in quality-of-life due to adverse effects of interferon treatment. Bone Marrow Transplantation (2001) 27, 511–515. [ABSTRACT FROM AUTHOR]

The number of CD34+ cells has been described as the best parameter for predicting the quality of engraftment in peripheral blood progenitor cell (PBPC) transplantation in the early post-transplant period. In this study we have determined the optimal number of CD34+cells in order to maintain engraftment in the long term in a series of 100 patients receiving autologous PBPC transplantation. Based on our previous experience on the speed of early hematopoietic recovery, four subgroups of patients were established: patients infused less than 0.75 × 106/kg CD34+ (n = 9), 0.75 to 1.25 (n = 24), 1.25 to 2.0 (n = 37) and more than 2.0 (n = 30). These groups were designated as low, intermediate-low, intermediate-high and high CD34 groups, respectively. Transitory loss of neutrophil engraftment was observed in 67%, 30%, 16% and 6% of patients in the four mentioned CD34 groups respectively, with statistically significant differences between the different groups. Significant differences were also observed between the low CD34 group and the rest of the groups as regards platelet and red blood cell transfusion requirements, fever episodes, days of hospitalization and antibiotic requirements throughout the first year. Our results show that the dose of CD34+ cells influences engraftment also in the late post-transplant period, and correlates with transfusion and antibiotic requirements, fever episodes and days of hospitalization during the first year post-transplant. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess which factors influence hematopoietic function long term after transplantation. For this purpose, we have analyzed a series of 79 patients who underwent autologous transplantation. None of them received any further chemotherapy or radiotherapy after transplant. All patients were disease-free 1 year after autologous transplantation. Late impairment of hematopoietic function was defined as the presence of non-transient peripheral blood cytopenias, detected 6 and 12 months after autografting. Before transplantion, 38.7% of patients showed peripheral blood cytopenias. Six and 12 months after transplantation, cytopenias presented in 44.2% and 42.4% of patients, respectively. Cases displaying cytopenias 6 months after transplantation had received a significantly lower dose of CFU-GM and CD34+ cells than patients without cytopenias (P = 0.012 and P= 0.04, respectively). The same correlation, with even higher statistical significance, was observed 12 months after transplant (P = 0.007 and P = 0.005). Alkylating agents and radiotherapy administered prior to transplantation and age did not seem to influence the presence of permanent cytopenias. The incidence did not vary significantly according to the stem cell source (bone marrow or peripheral blood). The number of CFU-GM and CD34+ cells infused was the most important factor for maintenance of adequate hematopoiesis. [ABSTRACT FROM AUTHOR]

Secondary myelodysplastic syndromes (MDS) are increasingly being reported after autologous transplantation. Transient dysplastic changes have also been observed after this type of treatment. However, to the best of our knowledge no systematic morphological analysis has been perfomed to determine the influence of stem cell transplantation on bone marrow morphology. In 53 patients undergoing autologous transplantation, we evaluated the bone marrow, before and 6 and 12 months after the transplant, in order to analyze the appearance of dyshemopoietic changes, assessed according to a pre-established score. We also studied 25 bone marrow samples obtained at the time of diagnosis, prior to treatment, but we did not find morphological atypia. Six months after transplant, cellularity and thrombopoiesis had decreased in 38% and 49% of patients respectively, although 1 year after the process they were normal in most cases. Myelodysplasia was already present in bone marrow before transplantation and continued to be in evidence for a long time afterwards. This suggests that chemotherapy and radiotherapy used prior to transplantation are responsible for dysplastic changes. The myeloid line was the most affected with 100% of patients showing dysgranulopoiesis 1 year after autografting. Cytopenias were observed in 51% and 44% of patients 6 and 12 months after transplantation. Moreover, concomitant presence of cytopenia and myelodysplasia was observed in 37.7% of patients at 6 months after transplantation and 25% at 12 months, and therefore they could be diagnosed with MDS. These data contrast with the incidence of secondary MDS reported in earlier publications. According to these findings, the value of the French–American–British Co-operative Group criteria for the diagnosis of MDS following autologous transplantation is questionable. Moreover, since dyshemopoietic features are almost always present after autologous transplant, morphological criteria are not... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the use of vitamin D as a treatment for chronic graft versus host disease (GVHD).

A letter to the editor about the use of vincristine in the treatment of transplantation-associated thrombotic microangiopathy is presented.

Hemorrhagic cystitis (HC) is a common complication following hemopoietic stem cell transplantation (HSCT), its incidence ranging from 7 to 52% of all patients. Late occurring HC frequently results from viral infections. We describe a patient who developed severe polyomavirus-associated HC, which responded dramatically to a single dose of intra-muscular vidarabine. Previous studies show an improvement in HC with vidarabine therapy, but to date only the intravenous route of administration has been described and responses described take from several days to weeks. This report confirms the safety and efficacy of vidarabine administered intramuscularly when used in patients with an adequate platelet count, thereby making its use feasible when intravenous vidarabine is not available. Bone Marrow Transplantation (2000) 26, 1229–1230. [ABSTRACT FROM AUTHOR]

Patients with hypereosinophilic syndrome (HES) display a very heterogeneous clinical picture ranging from asymptomatic cases to very aggressive forms. We report a 38-year-old woman with progressive HES who developed severe myelofibrosis and was treated by allogeneic stem cell transplantation, using peripheral blood (PBSCT) instead of bone marrow as the source of progenitor cells, after conditioning with cytoxan and busulphan. To the best of our knowledge, this is the first case of HES with myelofibrosis treated with PBSCT. The patient remains alive 8 months post-PBSCT, and bone marrow fibrosis has significantly decreased following transplantation. Bone Marrow Transplantation (2000) 25, 217–218. [ABSTRACT FROM AUTHOR]