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Objective@#To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients.@*Methods@#200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018.@*Results@#The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response.@*Conclusions@#Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.
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Objective@#To compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) .@*Methods@#Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively.@*Results@#①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3rd month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) .@*Conclusion@#HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.
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Objective To analyze the clinical pathology features of light-chain amyloidosis associated renal disease,and investigate the survival influential factors. Method From January 1998 to March 2009,25 patients with light-chain amyloidosis associated renal disease were reviewed and followed up.Results Of the 25 patients with light-chain amyloidosis associated renal disease,median age was 57(37-69) years old and lamda light-chain predominated (88% ,22/25). Heavy proteinuria and nephrotic syndrome with peripheral edema were typical clinical presentations. Renal biopsy showed that amyloid deposition of light-chain amyloidosis associated renal disease involved the glomeruh mostly, with mesangial area widening. Median survival of all patients was 24.4 months after diagnosis. The estimated 1,2,3 year survival rate was (65 ± 10 )%, (46 ± 12 )% and (15 ± 12 )% respectively. There was significant difference in median survival between the two groups (24.7 months in the group of 14 patients with isolated kidney affected,16.4 months in the group of 11 patients with kidney and other organs involved,P = 0.03). By univariate analysis, kidney associated with other organs amyloidosis and renal dysfunction were relevant to prognosis (P ＜ 0.05) and heart involvement was probably relevant (P = 0.06),whereas sex,age,plasma cell ratio,serum albumin level and hemoglobin level had no relation(P＞ 0.05 ). Multivariate analysis revealed that renal dysfunction at the time of diagnosis was a significant and independent prognostic factor for survival (P ＜0.05). Conclusions Renal dysfunction at the time of diagnosis is the best predictor of survival. The presence of amyloidosis in organs other than the kidney, such as advanced cardiac amyloidosis, predicts a poor survival.
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Objective To compare the clinical efficacy and complications of allogeneic peripheral blood stern cell transplantation (Allo-PBSCT) and immunosuppressive therapy (IST) for severe aplastic anemia(SAA). Methods Twenty-five patients with SAA underwent allogeneic HLA-matched sibling donor PBSCT(n = 12) and IST (n = 13). PBSCT group received conditioning regimen of cyclophosphamido(Cy) in combination with antithymocyte globulin(ATG). IST group received ATG followed by cyclosporine A (CsA).The short-term and long-term effects and complications were investigated. Results The mean time of recovery in the absolute neutrophil count (ANC), platelet and hemoglobin (Hb) in PBSCT group [(13.5±2.3), (23.5±4.1), (82.7±6.1)d, respectively]was shorter than those in IST group [(32.6±3.5), (73.8±6.2), (296.4±12.5)d, respectively]and there were statistical differences between two groups(P<0.05). But the one-year treatment effect between two groups showed no difference (P>0.05). There were no statistical differences in 3-year survival and overall survival rate between two groups (P>0.05). However, statistical difference was observed in overall relapse rate (P<0.05). The common complication in two groups was virus infection including cytomegalovirus (CMV) and varicella zoster virus (VZV), but there was no statistical difference in the incidence of virus infection between them (P>0.05). Conclusions Both allo-PBSCT and IST are effective methods for treating patients with SAA. PBSCT is considered preferentially in clinic, because of its advantages in faster hematopoietic engraftment, lower relapse rate and no increased complication.
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Objective To investigate early reduction of the dose of immunosuppressive drug after allogeneic peripheral blood stem cell transplantation(allo-PBSCT)for patients with refractory or relapsed leukemia.Methods Between Janaury 2004 and December 2006,15 patients with relapsed or refractory leukemia in Department of Hematology,the First Affiliated Hospital,Sun Yat-Sen University and Institute of Hematology & Blood Diseases Hospital,CAMS & PUMC,received allo-PBSCT from their relatives,12 from HLA-identical siblings.The preparative regimens included BuCy and TBICy with or without cytarabine.Cyclosporine A(CsA)or tacrolimus was used for graft-versus-host disease(GVHD)prophylaxis,with rapid decreasing starting on day 30 of post transplant if no GVHD appeared in receipts of matched sibling tranplantation.Results(1)Faster engraftment was achieved in all patients.Grade Ⅰ~Ⅱ acute GVHD appeared in 5 patients.Chronic GVHD occured in 7 of 11 evaluable patients.(2)Of 9 patients with an lower CsA or tacrolimus dosage,only 1 developed grade Ⅰ acute GVHD,4 chronic GVHD,2 extramedullary relapse.(3)After a median follow-up of 328 days,8 patients has leukemia-free-survival(LFS),4 relapsed,and only 1 had transplantation-related mortality(TRM)in the first 3 months post-transplant.The estimated LFS at 1 year and 2 years was 51% and 25%,respectively.Conclusion Patients with advanced leukemia might benefit from allo-PBSCT with significant lower treatment failure incidence.Dose reductions of CsA and tacrolimus in early transplant might enhance graft-versus-leukemia effect,and improve long-term LFS.