摘要:

AbstractMyeloablative therapy supported by autologous bone marrow or blood stem cell transplantation was assessed in 41 patients who had multiple myeloma resistant to vincristine‐doxorubicin by continuous infusion with high‐dose dexamethasone (VAD) or other high‐dose dexamethasone regimens. In patients who had high or intermediate tumor mass, the myeloma cell mass was reduced by more than 75% in 56% of patients and the survival time quadrupled in comparison with that of a matched control group. Later treatment resulted in a lower response rate and shorter remission. Current myeloablative regimens supported by autologous stem cells provided a useful treatment for patients who had advanced primary resistant multiple myeloma. Such treatment should be given early in the disease course to provide the best chance for remission, collecting blood stem cells with facility, and preventing complications that would increase the risk of the proc

ISSN:1066-5099    

DOI:10.1002/stem.5530130718

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractAnalysis of prognostic factors has been made in 369 allogeneic transplants for multiple myeloma reported to the registry of the European Group for Blood and Bone Marrow Transplantation (EBMT). Favorable prognostic factors for obtaining a complete remission (CR) were stage I at diagnosis (CR 77%), one line of treatment before conditioning (CR 52%), CR before conditioning (CR 60%), and Ig A or light chain myeloma (CR 43% and 42%). Factors that predicted significantly for favorable survival in a univariate analysis included having received only one line of treatment, female sex, stage I at diagnosis, stage I at conditioning and a β2‐Microglobulin less than 4 mg/l. Favorable post‐BMT factors consisted of obtaining a CR following BMT and not being in graft‐versus‐host disease stage III or IV. A multivariate analysis of pre‐BMT factors showed that the sex of the patient and the number of lines of treatment pretransplant were independent prognostic factors.Allogeneic BMT is a promising treatment method for patients who have received only one line of treatment, particularly if they are of the female sex. BMT late in the course of the disease is usually un

ISSN:1066-5099    

DOI:10.1002/stem.5530130719

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractAllogeneic bone marrow transplantation (BMT) was first explored for the treatment of multiple myeloma (MM) in the mid 1980s. Since then, there has been a rapidly growing clinical demand for the use of this modality of treatment, so that the number of patients receiving worldwide transplants from HLA‐identical siblings is actually estimated to be at least several hundreds. Although it is difficult to compare results between different centers because of differences in patient characteristics, selection criteria for transplantation and conditioning regimens, a certain number of conclusions have emerged from these experiences. There is evidence that allogeneic BMT performed in different phases of MM and with different conditioning regimens yields a high frequency of complete remissions (CR), in the range of 50% to 60%, and long‐term survival and remission rates, both averaging approximately 20%. Although a toxic‐related mortality rate of 40% has been consistently reported for many years, the outcome of patients in whom BMT was performed as consolidation of remission has recently improved. Prior responsiveness to conventional chemotherapy, also the presence of low tumor cell mass (both at diagnosis and before transplant) predicts for increased CR rate (up to 70% or more), as well as long‐term survival and remission rates (both averaging approximately 50%). The continued relapse‐free survival, up to and beyond ten years, reported for some of these patients provides strong evidence that allogeneic BMT has the potential ability to cure MM, probably as the result of an immunologic effect of the infused donor's marrow T lymphocytes against residual myeloma cells (graft‐versus‐myeloma). It can be concluded that allogeneic BMT is an effective, potentially curative treatment strategy for carefully selected MM patients with unfavorable prognostic features

ISSN:1066-5099    

DOI:10.1002/stem.5530130720

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractEighteen French centers reported 133 autologous stem cell transplantations performed after first remission induction in multiple myeloma. The source of stem cell was marrow (81 cases), blood (51 cases) or marrow plus blood (1 case). The immediate outcome after transplantation was 49 (37%) complete remissions (CR; 13 maintained, 36 achieved), 61 (46%) partial remissions, 17 failures and 5 toxic deaths. With a median follow up of 35 months, the median remission duration was 33 months, the median time to treatment failure was 22 months. The median overall survival was 46 months, 54 months for the 103 patients responding to primary treatment and 30 months for the 30 nonresponders. In univariate analysis, the outcome was influenced by age, Ig isotype, initial β2‐Microglobulin level, response to initial chemotherapy, plasma cell marrow involvement at the time of harvest, albumin and β2‐Microglobulin level at the time of transplantation and CR achievement after transplantation. In multivariate analysis, the most important prognostic factor was the quality of response after transplantation.The conditioning regimen and the source of stem cell had no significant impact on immediate and long‐term results. Maintenance therapy with a interferon did not appear to prolong remission duration or survival.Autologous stem cell transplantation is an effective consolidation for patients responding to primary treatment and a salvage therapy for some nonresponding patients. This approach has to be compared to conventional chemotherapy in prospective randomized studies. The critical impact of CR achievement on survival implies new strategies in order to increase the

ISSN:1066-5099    

DOI:10.1002/stem.5530130721

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractAutologous hematopoietic stem cell transplantation was used for treatment of 384 patients with multiple myeloma in 37 centers during the years 1986–1994. An analysis of prognostic factors was performed in 207 of these patients. One hundred forty one were males and 66 females, and median age was 49 years (range, 24–68). Actuarial survival at 78 months is 45%. Factors associated with a good prognosis were: response on chemotherapy immediately pretransplant, administration of only one treatment regimen, a low serum‐β2‐Microglobulin value at diagnosis and the use of a conditioning regimen including melphalan. In a multivariate analysis, response status pretransplant, age<45 years, melphalan conditioning and non‐TBI conditioning were independently predictive for longer survival, while transplantation after only one line of primary treatment and isotype other than light‐chain were of borderline significance. Post‐transplant alpha‐interferon treatment was associated with improved survival in responsive patients. Eighteen patients treated in one center (Huddinge) passed a double autograft program, and 14 are in continuous complete remission ([CR]; n = 10) or good partial remission (n = 4) at a median time of 17 months after the first transplant (range, 2–38). In five CR patients, polymerase chain reaction (PCR)‐analysis of the clone‐specific immunoglobulin‐rearrangement was performed, and four are PCR‐negative up to 33+ months after the first transplantation. We conclude that autografting in myeloma is most effective when applied early in the course of disease in younger, chemotherapy‐responsive patients. Alpha‐interferon maintenance treatment seems to be beneficial with respect to improved survival. Repeated cycles of high‐dose chemo‐radiotherapy with autologous stem cell rescue can induce a very high response rate, where the absence of minimal residual disease in CR patients has been demonstrated by

ISSN:1066-5099    

DOI:10.1002/stem.5530130722

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:1066-5099    

DOI:10.1002/stem.5530130723

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractIn an attempt to offset the impaired hematopoietic progenitors' mobilization and collection which are frequently encountered in multiple myeloma (MM), we have started a pilot study to evaluate the ability of a combination of high‐dose melphalan (HDM) and sequential s.c. administration of recombinant human interleukin 3 (rhIL‐3) and rh‐granulocyte colony‐stimulating factor (G‐CSF) to mobilize blood cells (BC) in MM patients. Two different schedules for administration were successively tested. Schedule A consisted of IL‐3 (5 μg/kg/d) from day 7 to day 11 after HDM followed by G‐CSF (5 μg/kg/d) from day 12 to day 20. Under schedule B, HDM was followed by IL‐3 alone at the same dosage from day 1 to day 3, IL‐3 and G‐CSF (idem) from day 4 to day 7 and G‐CSF alone from day 8 until completion of apheresis. Two patients (one previously untreated, one having received prior chemotherapy for one year) underwent schedule A; three patients (one previously untreated, two pretreated) underwent schedule B. The post‐HDM aplasia was not shortened in schedule A patients in comparison to what we usually observed following HDM alone (25 days) correlated with a very moderate two‐ to three‐fold CD34+cell increase. Only one patient was further transplanted with apheresis products: the post‐transplant granulocyte recovery was slower than usual (16 days versus 12 days) while platelet count never recovered over 20 × 109/l. In contrast, the post‐HDM aplasia was significantly shortened in two of the schedule B patients (3 to 10 days) and was followed by a 25‐ to 165‐fold increase in CD34+cells. These two patients underwent further BC transplant which was characterized by shortened granulocyte count nadir (9 days) and accelerated sustained platelet recovery (10 to 14 days). In the third patient, the hematopoietic recovery was delayed longer after schedule B and was preceded by a transient appearance of consistent rates of plasmacytoid cells in peripheral blood, suggesting a cytokine‐related mobilization of myeloma cells. However, schedule B, comprising an IL‐3/G‐CSF overlap, seems to better enhance BC mobilization than schedule A does and may offset the inhibition (induced by either the disease or melphalan) of hematopoiesis in high‐grade MM. Yet, the risk of concomitant tumor cell mobilization will require extreme caution when

ISSN:1066-5099    

DOI:10.1002/stem.5530130724

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractSince 1986, we have treated young patients with aggressive multiple myeloma (MM) by high‐dose chemotherapy (HDC) and total body irradiation (TBI) followed with autologous blood stem cell transplantation (ABSCT). To evaluate this strategy: 1) We conducted a phase II trial that included 63 patients. Within a median follow‐up of five years after transplantation, overall survival was 60% and median event‐free survival was four years, and 2) In the early 1990s, we initiated a prospective trial where, after collection of chemotherapy‐mobilized ABSC, patients under 55 years of age with newly diagnosed MM were randomly assigned either to HDC and TBI supported with ABSCT (high‐dose therapy [HDT] arm) or to a conventional vincristine, melphalan, cyclophosphamide and prednisone (VMCP) regimen (VMCP arm). In the latter, HDT with ABSCT was performed as a rescue therapy, in case of primary resistance to VMCP or at relapse in responders.As of June 1994, 167 patients have been enrolled since a median time of 26 months. Fourteen (8%) could not be randomized. Among the randomized patients (n = 153), 30 deaths were observed, 13 in the HDT group and 17 in the VMCP group (p= 0.28, two‐sided log rank test). Overall survival rates at two years were estimated at 78% for all 167 patients, at 82% in the HDT group and at 67% in the VMCP group.ABSC, provided they are collected early in the disease course, allow a great majority of myeloma patients to receive HDT. Additional follow‐up is required to better assess if HDT with ABSCT used as front‐line therapy confers an advantage over conventional therapy with earl

ISSN:1066-5099    

DOI:10.1002/stem.5530130725

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe aim of the study was to evaluate the feasibility and the efficacy of high‐dose chemoradiotherapy followed by autologous hematopoietic stem cell support with peripheral blood progenitor cells (PBPC) harvested after high‐dose cyclophosphamide (HDCYC) treatment in patients with high‐risk multiple myeloma (MM). Inclusion criteria were: age less than 65 years and high‐risk MM defined as stage II MM, stage III MM, refractory or relapsed MM. The design of the study was: 1) HDCYC ± hematopoietic growth factors followed by PBPC collection, and 2) high‐dose melphalan combined with total body irradiation (or busulfan for previously irradiated patients) followed by PBPC reinfusion (ABPCT). All 60 patients completed the procedure except two who died from infection after HDCYC and another of acute cardiac failure after reinfusion of PBPC. Out of the 60 evaluable patients, three failed to respond while the other 57 achieved either a partial (n = 33) or complete (n = 24) response. Thirty‐one patients progressed or relapsed after a median duration of response of 15 months (range: 3–43). The median follow‐up for the other 26 responder patients was 24 months (range: 2–66). Twenty‐one patients died, 18 of MM (2 after failure, 16 after relapse) and three responders of lung cancer (n = 1) and infection (n = 2). In conclusion, this study shows that this therapeutic approach is fe

ISSN:1066-5099    

DOI:10.1002/stem.5530130726

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:1066-5099    

DOI:10.1002/stem.5530130727

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY