Autologous stem cell transplantation in first remission is associated with better progression-free survival in multiple myeloma

Autologous stem cell transplant (ASCT) is standard consolidation therapy in management of multiple myeloma (MM) patients. We reviewed records of all consecutive MM patients who underwent ASCT with high-dose melphalan at our center from year 2002 to 2016. A total of 141 ASCT were conducted (90 males and 51 females) with median age of 55 years (23–68 years). Median time from diagnosis to transplant was 7 months (3–79), with majority of patients underwent transplant in first remission, while 17 (12%) patients received transplant beyond first remission. Eighty-three percent patients obtained CR/VGPR post-ASCT. Transplant-related mortality was 2.1%. At a median follow up of 54 months, mean overall survival (OS) and progression-free survival (PFS) group were 128.3 months (95% C.I. 111.9–144.7 months) and 73.8 months (95% C.I. 57.7–89.9 months), respectively. On univariate analysis, OS was adversely affected by renal insufficiency (p?=?0.024), while OS was better with CR/VGPR post-ASCT (p?<?0.001) and lenalidomide maintenance therapy (p?=?0.009). PFS was affected by CR/VGPR pre-ASCT (p?=?0.021), CR/VGPR post-ASCT (p?<?0.001), and transplant in first remission (p?=?0.034). On multivariate analysis, lenalidomide maintenance (versus thalidomide) (p?=?0.007) and CR/VGPR response post-ASCT (p?=?0.0003) were found to be predictors for better OS and CR/VGPR response at transplant for better PFS (p?=?0.038). Transplant in first remission versus beyond first remission showed a trend for better PFS (p?=?0.073). Conclusion: Majority of patients obtained CR/VGPR post-ASCT. Longer PFS was seen with patients who were transplanted in first remission.     

多发性骨髓瘤的自体造血干细胞移植治疗

多发性骨髓瘤(multiple myeloma,MM)是一种好发于中老年人的血液系统恶性疾病,由骨髓中的浆细胞单克隆性增生引起。典型临床表现为骨骼系统破坏,如病理性骨折、本-周蛋白尿、贫血以及慢性肾功能不全,并伴随高钙血症、血沉增快及免疫球蛋白电泳出现单克隆免疫球蛋白峰等。MM常规化学治疗(化疗)反应率低,其中位生存期多为2～3年。临床研究证明经自体造血干细胞移植(AHSCT)治疗可     

Autologous and allogeneic stem cell transplantation in multiple myeloma

Multiple myeloma is still an incurable disease. The standard conventional chemotherapy comprises melphalan and prednisone (MP). Combination chemotherapy regimens could not improve the median survival of 36 months observed with MP. In the French IFM90 study, HD therapy with TBI plus melphalan 140 mg/m2 was shown to prolong overall survival and progression-free survival compared to conventional treatment. Nonetheless, most patients eventually succumb due to disease progression. Allogeneic transplantation may induce long-term remissions and even cure, but is hampered by a high transplantation-related mortality (TRM). Currently, efforts are made to reduce this TRM and to evaluate the graft-versus-myeloma effect.     

Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma

We evaluated toxicity, engraftment, chimerism, graft-versus-host disease (GVHD), and response to a dose-reduced allograft after cytoreductive autografting in 17 patients with advanced stage II/III multiple myeloma (MM). After autografting with melphalan (200 mg/m2) the patients received after a median interval of 119 days (range 60-210) a dose-reduced regimen consisting of fludarabine (180 mg/m2), melphalan (100 mg/m2), and antithymocyte globulin (3 x 10 mg/kg) followed by allografting from related (n = 7), mismatched related (n = 2), or unrelated (n = 8) donors to induce a graft-versus-myeloma effect. After dose-reduced allografting all patients became neutropenic (< 0.2 x 10(9)/L) for at least 8 days. All patients engrafted with a median time for leukocyte (> 1 x 10(9)/L) and platelet (> 20 x 10(9)/L) counts of 16 (range, 11-24) and 23 days (range, 12-43), respectively. Complete donor chimerism was detected after a median of 30 days (range, 19-38). Acute GVHD stage II occurred in 4 patients (25%) and grade III GVHD in 2 patients (13%). Chronic GVHD developed in 40% of the patients, but only 1 patient experienced extensive chronic GVHD requiring further immunosuppressive therapy. Two patients died of alveolar hemorrhage and pneumonia, resulting in a day 100 mortality rate of 11%. The rate of complete remission with negative immunofixation increased from 18% after autografting to 73% after allografting. After a median follow-up of 17 months after autologous and 13 months after allogeneic transplantation 13 patients are alive and 12 of them free of relapse or progression. The tandem auto-allotransplant protocol is highly active and provides rapid engraftment with complete donor chimerism and tolerable toxicity.     

Autologous peripheral blood stem cell transplantation as first line treatment of multiple myeloma: an Italian Multicenter Study

BACKGROUND AND OBJECTIVE: The outcome of patients with multiple myeloma (MM) has not changed markedly since the introduction of melphalan and prednisone. In recent years several studies have investigated the role of intensive therapy followed by infusion of autologous peripheral blood stem cells (PBSC) together with the administration of hematopoietic growth factors. In this study we evaluated the feasibility and efficacy of a PBSC transplantation program for patients with de novo MM in a multicenter setting. DESIGN AND METHODS: In a non-randomized controlled trial 52 patients with de novo MM from 6 Italian centers underwent a three phase treatment strategy including 3 cycles of VAD-like chemotherapy for initial debulking, followed by high-dose cyclophosphamide (HD-CY) and collection of PBSC, that were transplanted after a conditioning regimen with melphalan plus busulfan. Maintenance treatment was a conventional dose of interferon, given until relapse. Actuarial survival and response duration curves were plotted according to Kaplan and Meier's method; the groups were compared using the log rank test. Response rates were compared by the c(2) test; multivariate analysis was performed according to the stepwise regression model. RESULTS: Overall 39/52 (75%) of patients responded, with a complete remission (CR) rate of 31%. After a median follow-up of 55 months, median duration of event-free survival (EFS) and overall survival (OS) are 21 and 57 months, with 24% and 48% probabilities of being event-free and alive after 6 years, respectively. Among the group of 39 responders, CR was significantly associated with prolonged response and survival (2 deaths and 6 relapses/16 patients) as compared with PR (11 deaths and 15 relapses/23 patients), and remained the only significant variable also in a multivariate analysis. Myelosuppression did not protract beyond one week in transplanted patients; extra-hematologic toxicity was very low. INTERPRETATION AND CONCLUSIONS: This multicenter study confirms the feasibility of an aggressive approach to de novo MM patients. Additional confirmation is given of the increased rate of CR, and the significant prolonged survival observed in complete responders. In this experience the association melphalan plus busulfan was shown to be effective, at least as part of conditioning regimens, in the transplant strategy.     

Myelodysplastic syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma

Long-term survivors after autologous peripheral blood stem cell transplantation (APBSCT) for lymphoma or Hodgkin's disease are known to have a high risk of developing myelodysplastic syndrome (MDS), but the risk of MDS is not clear for patients transplanted for myeloma. We reviewed the outcomes for 82 myeloma patients who underwent APBSCT at our center. The group included 47 men and 35 women of median age 56 years (range: 37-74 years). Median time from diagnosis to APBSCT was 8.2 months (range: 2.6-86.1 months). Before coming to transplantation, 28% had received oral melphalan (MEL), 98% received other chemotherapy and 34% received radiation. A single APBSCT was provided for 68, and 32% underwent APBSCT more than once. High-dose MEL alone was used as the preparative regimen for 83%, and the remainder received at least one APBSCT with a more intensive preparative regimen. Ten patients (12%) developed MDS. The 5-year cumulative incidence is 18% (95% confidence interval, 9-30%). There were no demographic factors associated with an increased risk of developing MDS. Median survival after the diagnosis of MDS was 18 months. There is a relatively high risk of MDS after APBSCT for myeloma, and optimal therapy has not been established for these patients.     

Maintenance treatment with recombinant alpha interferon after autologous bone marrow transplantation for aggressive myeloma in first remission after conventional induction chemotherapy

Twenty patients (median age 57 years) with high tumor mass myeloma in first remission after conventional chemotherapy received a two-phase treatment: autologous bone marrow transplantation (ABMT) using a preparative regimen of high dose melphalan plus total body irradiation followed by maintenance treatment with recombinant alpha interferon. Before ABMT all patients were in partial remission, while after ABMT 10 (50%) achieved complete remission, and 10 remained in partial remission (with a 90% decrease in measurable paraprotein in 7/10). With a median follow-up of 19.8 months (12.2-33.5) after diagnosis and 13 months (4-25) after ABMT, the Kaplan-Meier 2-year post-ABMT probability of progression-free survival was 85% (95% CI = 58.7-95.8%). None of the 10 patients in complete remission has relapsed. No toxic death occurred. Alpha interferon was introduced early after ABMT (2.7 months) and was well tolerated. This strategy may represent an advance in the management of aggressive myeloma.     

Prolonged responses after autologous stem cell transplantation in African-American patients with multiple myeloma

Multiple myeloma (MM) has a double incidence in African-American (AA) than in non-AA patients and previous studies have shown a higher mortality in the former patient population. Here, we retrospectively analyzed the results of autologous stem cell transplantation (ASCT) in 38 AA and 32 non-AA consecutive patients. The two groups were comparable at diagnosis for age, stage of the disease, cytogenetic abnormalities, beta(2) microglobulin and albumin blood levels, and plasma cell marrow infiltration. The rates of complete and partial response observed in AA and non-AA patients after induction chemotherapy (9 and 42 vs 13 and 33%) and at 2 months (31 and 25 vs 30 and 20%) following ASCT were similar. At 6 months after ASCT, a greater relapse rate was observed in non-AA patients (P=0.009). At a median follow-up of 26 months, AA patients had a greater event-free survival (P=0.02) than non-AA patients, whereas overall survival was comparable in the two groups. The initial finding that AA patients with MM, compared to non-AA patients, had more prolonged responses and comparable survival after ASCT suggests that intensified chemotherapy is equally effective in patients of various ethnicities.     

High-dose therapy/autologous stem cell transplantation in patients with chemosensitive multiple myeloma: predictors of complete remission

High-dose therapy (HDT) followed by autologous stem cell support is widely used as intensification treatment in patients with multiple myeloma (MM) responsive to the initial chemotherapy. However, there is growing evidence that only the subset of patients who achieve complete remission (CR) actually benefit from this approach. The aim of this study was to identify pretransplant predictors of CR in responding myeloma patients intensified with HDT. A total of 59 patients with chemosensitive disease received myeloablative therapy. The intensification regimen consisted of MEL-200 (23), MEL-140/TBI 12 Gy (21) or busulfan-based regimens (15). Serum and urine negative immunofixation were required for CR. After HDT, the CR rate increased from 8 to 37%. For the overall series, the median event-free survival (EFS) and overall survival (OS) from the initiation of therapy were 41 and 68 months, respectively. Patients who achieved CR had an EFS (median 47 vs 36 months; P=0.023) as well as an OS (median not reached vs 60 months; P=0.006) significantly longer than those attaining a lower degree of response. Finally, the pretransplant features significantly associated to CR were a low M-protein size (serum 相似文献   

Long-term follow-up of multiple myeloma after autologous hematopoietic stem cell transplantation:a single center results

正Objective To evaluate the efficacy and long-term outcome of a combined protocol for multiple myeloma(MM),including induction therapy,autologous hematopoietic stem cell transplantation(ASCT)and consolidation and maintenance therapy.Methods Clinical records of 144 patients with MM from January 1,2005 to February 1,2016 were retrospectively analyzed.Results The overall response rate(ORR)after ASCT was 100.0%,     

Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry

OBJECTIVE: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. METHODS: Only patients with SSc, treated by HSCT in European phase I-II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). RESULTS: Given as median (range). Among 57 patients aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5-81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). CONCLUSION: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.     

Differential humoral responses against heat-shock proteins after autologous stem cell transplantation in multiple myeloma

Heat-shock proteins (HSP) are important molecules in the pathogenesis of multiple myeloma (MM). Their blockages by drugs or cellular immune response have been investigated, and a possible association with the presence of oligoclonal bands (OB) has been postulated in patients with MM after allogenic stem cell transplantation. The aim of the present study was to ascertain the serum antibody levels against three HSP (60, 70 and 90) by ELISA in patients with MM in complete remission after autologous stem cell transplantation (ASCT), with or without OB, and compare them with those patients with stable gammopathy of undetermined significance (MGUS) and healthy controls. Our results in samples after ASCT showed no differential levels of anti-HSP according to the presence or absence of the oligoclonal response. However, higher levels of anti-HSP90 were found in patients with stable MGUS in comparison with MM patients (p?=?0.004). In the same line, a longer progression-free survival was observed in those patients who presented higher anti-HSP90 levels after ASCT (p?=?0.042). These results suggest, for first time, the potential of anti-HSP90 humoral immune response for long-term control of malignant plasma cell disorders.     

Impact of failed response to novel agent induction in autologous stem cell transplantation for multiple myeloma

The aim of this study was to evaluate the impact of the response to induction therapy on the long-term prognosis of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) in the era of novel agents (NAs). A total of 171 patients who were newly diagnosed with MM and underwent early ASCT were analyzed. One hundred ten had a NA-based induction therapy, and 61 patients had a non-NA-based induction therapy. After a median follow-up of 45.4 months, the 4-year overall survival (OS) and progression-free survival (PFS) from transplantation were 60.5 and 25.5 %, respectively, for the NA-based induction group and 54.6 and 15.6 %, respectively, for the non-NA-based induction group. Multivariate analyses revealed that the patients who had NA-based induction had a significantly shorter OS (P?<?0.001) and PFS (P?<?0.001) when at least a partial response (PR) was not achieved. In patients who did not receive NAs before ASCT, lack of at least a PR to induction therapy was not associated with a survival disadvantage. These findings suggest that, unlike pretransplantation induction before NAs, patients who do not respond to induction treatment using NAs may not derive a benefit from ASCT. The relevance of induction failure differs for corticosteroid- and NA-based induction.