Simple variables predict survival after autologous transplantation: a single centre experience in 181 multiple myeloma patients

Autologous stem cell transplantation (ASCT) has an important role in the treatment of multiple myeloma (MM) patients. The aim of our study was to analyse retrospectively the impact of selected simple parameters on the survival of patients with MM after ASCT, including age, type of M-protein, stage of MM, treatment response, and presence of renal impairment. A total of 181 MM patients were transplanted in our centre between 1995 and 2004. The median follow-up from transplant was 59 months. Following ASCT, 29% of patients were in complete remission (CR) and 62% in partial remission (PR); 35% of patients had very good partial response (VGPR). Median time to progression (TTP) and overall survival (OS) from start of therapy were 33.0 and 78.3 months, respectively. Significant prognostic parameters for poor survival after ASCT were: age at transplant > 60 years (P < 0.001), TTP < 20 months (P < 0.001), IgA type of monoclonal immunoglobulin (P = 0.045), renal impairment with serum creatinine > 177 micromol/l (> 2 mg/dl; P = 0.004), clinical stage III according to ISS (P = 0.002) and no achievement of CR and/or VGPR after ASCT (P < 0.001). The stage of the disease before ASCT did not significantly affect OS after ASCT.     

Role of high-dose melphalan with autologous stem cell transplantation in multiple myeloma patients receiving botezomib-containing induction therapy

To examine the role of high-dose melphalan therapy with autologous stem cell transplantation (HDM/ASCT) in the final outcomes of multiple myeloma (MM) patients receiving bortezomib-containing induction therapy (IT), we analyzed relationships between quality of response after IT including bortezomib or HDM/ASCT and survival. In total, 92 MM patients who received IT with bortezomib followed by HDM/ASCT were enrolled. The median follow-up was 28.0 months. Three-year progression-free survival (PFS) and overall survival (OS) were 41.1 and 72.0 %, respectively. A complete response (CR) after HDM/ASCT was a strong prognostic factor for PFS and OS (p = 0.002 and 0.001, respectively). Additionally, out of 67 patients who failed to achieve CR after IT, 36 (53.7 %) patients achieved CR after HDM/ASCT. PFS and OS in patients with CR after additional HDM/ASCT were similar to those in patients who had already achieved CR after IT. However, achievement of at least very good partial response following IT with bortezomib failed to improve PFS and OS (p = 0.35 and 0.11, respectively). Thus, we conclude that post-HDM/ASCT CR is the best prognostic factor for both PFS and OS regardless of response to bortezomib. Therefore, HDM/ASCT remains an important therapy in MM patients even after introduction of bortezomib IT.     

Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation

Minimal residual disease (MRD) assessment is standard in many hematologic malignancies but is considered investigational in multiple myeloma (MM). We report a prospective analysis of the prognostic importance of MRD detection by multiparameter flow cytometry (MFC) in 295 newly diagnosed MM patients uniformly treated in the GEM2000 protocol VBMCP/VBAD induction plus autologous stem cell transplantation [ASCT]). MRD status by MFC was determined at day 100 after ASCT. Progression-free survival (PFS; median 71 vs 37 months, P < .001) and overall survival (OS; median not reached vs 89 months, P = .002) were longer in patients who were MRD negative versus MRD positive at day 100 after ASCT. Similar prognostic differentiation was seen in 147 patients who achieved immunofixation-negative complete response after ASCT. Moreover, MRD(-) immunofixation-negative (IFx(-)) patients and MRD(-) IFx(+) patients had significantly longer PFS than MRD(+) IFx(-) patients. Multivariate analysis identified MRD status by MFC at day 100 after ASCT as the most important independent prognostic factor for PFS (HR = 3.64, P = .002) and OS (HR = 2.02, P = .02). Our findings demonstrate the clinical importance of MRD evaluation by MFC, and illustrate the need for further refinement of MM re-sponse criteria. This trial is registered at http://clinicaltrials.gov under identifier NCT00560053.     

Alpha-interferon maintenance treatment is associated with improved survival after high-dose treatment and autologous stem cell transplantation in patients with multiple myeloma: a retrospective registry study from the European Group for Blood and Marrow Transplantation (EBMT)

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.     

Autologous stem cell transplantation in multiple myeloma: improved survival in nonsecretory multiple myeloma but lack of influence of age,status at transplant,previous treatment and conditioning regimen. A single-centre experience in 127 patients

High-dose therapy with autologous stem cell transplantation (ASCT) has become the treatment of choice for symptomatic eligible patients with multiple myeloma (MM). We report our centre experience and analyse retrospectively the prognostic influence of pretransplant characteristics and transplant modalities on response and survival. A total of 127 MM patients (median age: 55.2 years) were transplanted between 1994 and 2001. In all, 69 patients had IgG, 28 IgA, 23 light chain, one IgD and six non secretory MM. At the time of autograft, 6% of patients were in complete remission (CR), 73% in partial remission (PR), 12% showed minor response to previous treatment and 9% had stable or refractory disease. Prior to autograft, 79% of cases had received only one line of chemotherapy and 21% two or more lines. All patients received PBSC support after conditioning with 200 mg/m(2) melphalan alone (100 patients) or melphalan and TBI (27 patients). We evaluated the influence of age (using as cutoff value the ages of 55, 60 and 65 years), type of MM, status pre- and post-ASCT, number of lines of previous regimens, time of ASCT from diagnosis, year of autograft, dose of reinfused CD34+ cells, plasma cell infiltration and beta(2)-microglobulin at diagnosis on overall (OS) and progression-free survivals (PFS) to define patients with better prognosis. Following ASCT, 15% of patients were in CR and 81% in PR, while only two patients progressed. Median OS and PFS from transplantation were 50.4 and 23.5 months, respectively. Median OS from diagnosis was 79.7 months. Transplant-related mortality was 2.3%. Low levels of beta(2)-microglobulin and the achievement of CR post-transplant correlated with longer PFS (P<0.03 and P<0.01, respectively). The median PFS was 36.1, 23.9, 21.1 and 16.4 months for nonsecretory, IgG, IgA and light chain subtypes, respectively. Age was not an important prognostic factor at a cutoff value of 55 or 60 years. We conclude that ASCT is a safe and effective procedure even in resistant cases. The outcome was independent of age, time from diagnosis, previous treatment and conditioning regimen, but there was a tendency for better survival in the nonsecretory patients.     

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.     

The impact of race on outcomes of autologous transplantation in patients with multiple myeloma

Multiple myeloma is the most common hematologic malignancy in African-Americans, with twice the mortality of Caucasians according to population based data. In the pretransplantation era, comparable conventional therapy has resulted in similar outcomes between African-Americans and Caucasians. However, there has been limited data on outcomes after high dose chemotherapy with autologous stem cell transplantation (ASCT). A retrospective analysis of Caucasian (n = 55) and African-American (n = 36) myeloma patients who underwent ASCT in an equal access health care system in the Department of Defense was performed. Presenting demographic variables, pre/post ASCT characteristics, overall mortality and relapse rates after ASCT were obtained. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier, and compared via log-rank testing. The median age at diagnosis for African-Americans = 52 years, Caucasians = 56 years (P = 0.009). There were no differences in presenting ISS stage, hemoglobin, calcium, or creatinine. African-Americans presented with higher CRP levels (P = 0.005), and a trend for less skeletal involvement (P = 0.10). Response to induction and ASCT was similar. Median PFS was 60.5 months (95% CI: 31.3-89.8 months) for African-Americans, 43.7 months (95% CI: 33.9-53.5 months) for Caucasians, HR of 1.3 (95% CI: 0.7-2.4), P = 0.46. Median OS was 95.2 months (95% CI: N/A) for African-Americans, 68.5 months (95% CI: 14.2-122.9 months) for Caucasians, HR of 1.4 (95% CI: 0.7-2.9), P = 0.41. In a cohort of myeloma patients who received autologous transplantation in an equal access health care system, there was comparable survival between African-Americans and Caucasians, suggesting that the historical increased mortality for African-Americans may be due to inequalities in access to care.     

Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: a prospective study from The Gel-Tamo Study Group

OBJECTIVE: Retrospective data shows that peripheral T-cell lymphoma (PTCL) patients sensitive to conventional chemotherapy for aggressive lymphomas may respond better if this treatment is consolidated with frontline autologous stem cell transplantation (ASCT). Here, we present data from a prospective phase II trial of high-dose chemotherapy and ASCT as a frontline consolidation therapy for aggressive nodal PTCL. METHODS: This study involved 26 gallium-scan-positive patients with high-risk nodal PTCL [excluding anaplastic lymphoma kinase (ALK) positive]. Patients received three courses of MegaCHOP before they were evaluated, and those that were gallium-scan-negative at this stage then received another course of MegaCHOP and ASCT. Patients who remained gallium-scan-positive received two courses of an IFE regimen (ifosfamide 10 g/m(2), etoposide 150 mg/m(2)/12 h on days 1-3) and if they at least achieved PR, they then received the transplant. RESULTS: Complete response (CR) was achieved by 12 patients (46%) after three courses of MegaCHOP and 12 patients received IFE as a salvage therapy. After the ASCT (n = 19), 89% of patients achieved CR. In contrast, six patients (23%) did not receive the transplant because of the progression of the disease (n = 5) or lethal toxicity (n = 1). One patient in first-line CR refused ASCT. After a median follow-up of 35 months, the overall survival (OS) and progression-free survival (PFS) at 3 yr was 73% and 53%, respectively. Moreover, the OS, PFS and disease-free survival (DFS) were 84%, 56% and 63%, respectively 2 yr after transplant in patients who received ASCT consolidation (n = 19). CONCLUSIONS: Early salvage therapy for patients with high-risk aggressive nodal PTCL that do not achieve CR after three courses of chemotherapy and ASCT frontline consolidation for chemosensitive patients may improve treatment outcome.     

LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed Hodgkin's lymphoma. We have analysed 67 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n=61) or primary refractory (n=6) Hodgkin's lymphoma. The 100-day treatment-related mortality was 3%. With a median follow-up of 67 months (range 3.3-161.0) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 68 and 64%, respectively. Probabilities for OS and PFS at 5 years for patients with chemosensitive relapse (n=40) were 81 and 78% versus 50 and 35%, respectively, for patients (n=27) with chemoresistant relapse (P=0.012 for OS, P=0.002 for PFS). In multivariate analysis mixed cellularity classical or lymphocyte-depleted classical histology subtype and haemoglobin level of 10 g/dl or less at the time of ASCT were identified as risk factors for worse OS, whereas stage III or IV disease at diagnosis and disease status at ASCT other than complete or partial remission predicted inferior PFS. LACE followed by ASCT is an effective treatment for the majority of patients with chemosensitive relapsed Hodgkin's lymphoma and a proportion of chemorefractory patients also benefit.     

The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantation for follicular lymphoma

The impact of the follicular lymphoma (FL) histologic grade on outcomes after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) is unknown. We evaluated 219 consecutive patients with grades 1-3 FL who underwent HDT and ASCT at our center. Overall survival (OS), progression-free survival (PFS), relapse and non-relapse mortality (NRM) was estimated for each grade after controlling for other predictive factors. The number of patients with grades 1, 2 and 3 FL was 106 (48%), 75 (34%) and 38 (17%), respectively. Five-year outcome estimates for the entire cohort included 60% OS, 39% PFS and 46% relapse (median follow-up=7.8 years). PFS and relapse were nearly identical among patients with grade 3 FL versus grades 1-2 FL after adjusting for other contributing factors (hazard ratio (HR)=0.90, P=0.68; HR=1.07, P=0.80, respectively). The hazard for mortality (HR=0.70, P=0.23) and NRM (HR=0.33, P=0.07) was non-significantly lower among patients with grade 3 FL compared to patients with grades 1-2 disease. Factors associated with inferior PFS included elevated lactate dehydrogenase (HR=1.52, P=0.03), chemoresistance (HR=1.82, P=0.02), > or =2 prior therapies (HR=1.8, P=0.03) and prior radiation (HR=1.99, P=0.003). These data suggest that the histologic grade of FL does not impact PFS or relapse following HDT and ASCT.     

Predictors of prolonged survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma

A total of 149 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with myeloablative (MAC; n = 38) or reduced-intensity conditioning (RIC; n = 110) regimens at MD Anderson Cancer Center were evaluated. Of the total, 120 (81%) patients had relapsed or had refractory disease. Median age of MM patients was 50 (28-70) years with a followup time of 28.5 (3-164) months. The 100-day and 5-year treatment related mortality (TRM) rates were 17% and 47%, respectively. TRM was significantly lower with RIC regimens (13%) vs. 29% for MAC at 100 days (P = 0.012). The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) was 35% and chronic GVHD was 46%. PFS and OS at 5 years were 15% and 21%, respectively. In multivariate analysis, allo-HCT for primary remission consolidation was associated with longer PFS (HR 0.35; 95% CI, 0.18-0.67) and OS (HR 0.29; 95% CI 0.15-0.55), while absence of high-risk cytogenetics was associated with longer PFS only (HR 0.59; 95% CI 0.37-0.95). We observe that TRM has decreased with the use of RIC regimens, and long-term disease control can be expected in a subset of MM patients undergoing allo-HCT. Further studies should be conducted in carefully designed clinical trials in this patient population.     

A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma

One hundred ten patients with multiple myeloma (MM) failing to achieve at least near-complete remission (nCR) after a first autologous stem cell transplantation (ASCT) were scheduled to receive a second ASCT (85 patients) or a reduced-intensity-conditioning allograft (allo-RIC; 25 patients), depending on the human leukocyte antigen (HLA)-identical sibling donor availability. There was a higher increase in complete remission (CR) rate (40% vs 11%, P = .001) and a trend toward a longer progression-free survival (PFS; median, 31 months vs not reached, P = .08) in favor of allo-RIC. In contrast, it was associated with a trend toward a higher transplantation-related mortality (16% vs 5%, P = .07), a 66% chance of chronic graft-versus-host disease and no statistical difference in event-free survival and overall survival. Although the PFS plateau observed with allo-RIC is very encouraging, this procedure is associated with high morbidity and mortality, and therefore it should still be considered investigational and restricted to well-designed prospective clinical trials. This trial is registered at ClinicalTrials.gov ID number NCT00560053.     

High-dose chemotherapy with autologous stem cell transplantation in extranodal NK/T-cell lymphoma: a retrospective comparison with non-transplantation cases

To determine the role of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in extranodal NK/T-cell lymphoma patients, we conducted a retrospective analysis. In our previous study, we searched for patients who had received HDC/ASCT and identified 16 eligible patients and compared the treatment outcome with historical control group (n=246). Nine patients received HDC/ASCT in the first (CR1) or second complete remission (CR2), while seven patients received HDC/ASCT as salvage. Twelve of 16 patients achieved or maintained CR after HDC/ASCT. Among the 12 patients, five patients relapsed. Estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates were 71.3+/-12.4% and 25.8+/-14.3%, respectively. There was a tendency of better survival in patients who received HDC/ASCT as compared to those who did not (P=0.091). In subset analysis, patients who underwent HDC/ASCT at CR (P=0.049) and patients with stage III or IV (P=0.001) had a favorable outcome. Patients with NKIPI 3,4 or EUNKTL, who underwent HDC/ASCT had more prolonged survival without statistical significance (P=0.055 and 0.056). In conclusion, HDC/ASCT may be considered as a treatment option for patients with extranodal NK/T-cell lymphoma, especially those in CR, with advanced disease (stage III/IV or EUNKTL) and high NKIPI scores.     

血清乳酸脱氢酶水平与初诊老年多发性骨髓瘤病人预后的相关性分析

目的探讨血清乳酸脱氢酶(LDH)与初诊老年多发性骨髓瘤(MM)临床指标的相关性及其预后意义。方法回顾性分析我院2009年7月至2016年1月年龄≥65岁的78例初诊老年MM病人的临床资料,并绘制病人的Kaplan-Meier生存曲线,分析初诊时血清LDH水平与病人预后的关系。根据病人的LDH水平分为LDH正常组和LDH升高组,并根据荧光原位杂交技术检测结果对60例资料完整的MM病人进行修正的国际分期系统(R-ISS)分期,比较其与国际分期系统(ISS)分期对预后判断的准确性。结果所有病人中位随访时间为16.5个月,初诊时LDH水平升高者占11.5%(9/78)。LDH正常组中位生存期(OS)和中位无进展生存期(PFS)分别为44.0个月、23.0个月,LDH升高组分别为14.0个月、12.0个月,2组间比较,差异有统计学意义(P<0.01)。COX多因素回归分析显示,LDH水平升高是老年MM病人OS的独立不良预后因素(HR=5.998,95%CI2.454~14.664,P<0.001)。另外,ISS分期Ⅱ期和Ⅲ期病人的中位OS差异无统计学意义(44.0个月比39.0个月,P=0.713),中位PFS差异也无统计学意义(26.0个月比20.0个月,P=0.569);而R-ISS分期Ⅱ期和Ⅲ期病人的中位OS差异有统计学意义(44.0个月比15.5个月,P<0.001),中位PFS差异无统计学意义(21.0个月比14.0个月,P=0.097)。结论LDH水平是判断老年MM病人预后的重要指标,基于其基础上的R-ISS分期在预后判断中要优于ISS分期。     

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma

Autologous stem cell transplantation (ASCT) improves survival in patients with previously untreated multiple myeloma (MM) and relapsed, chemotherapy-sensitive, aggressive non-Hodgkin lymphoma (NHL). Lower relapse rates seen in allogeneic stem cell transplantation have been related to early absolute lymphocyte count (ALC) recovery as a manifestation of early graft-verus-tumor effect. In ASCT, the relation between ALC recovery and clinical outcomes in MM and NHL was not previously described. This is a retrospective study of patients with MM and NHL who underwent ASCT at the Mayo Clinic between 1987 and 1999. The ALC threshold was determined at 500 cells/microL on day 15 after ASCT. The study identified 126 patients with MM and 104 patients with NHL. The median overall survival (OS) and progression-free survival (PFS) times for patients with MM were significantly longer in patients with an ALC of 500 cells/microL or more than patients with an ALC of fewer than 500 cells/microL (33 vs 12 months, P <.0001; 16 vs 8 months, P <.0003, respectively). For patients with NHL, the median OS and PFS times were significantly longer in patients with an ALC of 500 cells/microL or more versus those with fewer than 500 cells/microL (not reached vs 6 months, P <.0001; not reached vs 4 months, P <.0001, respectively). Multivariate analysis demonstrated day 15 ALC to be an independent prognostic indicator for OS and PFS rates for both groups of patients. In conclusion, ALC is correlated with clinical outcome and requires further study. (Blood. 2001;98:579-585)     

Outcome after autologous and allogeneic stem cell transplantation for patients with multiple myeloma: impact of graft-versus-myeloma effect

A total of 228 patients with multiple myeloma (MM), 166 patients receiving autologous transplantation (124 PBSC and 38 BM) and 66 patients receiving T-cell-depleted allogeneic transplantation were analyzed to compare overall survival (OS), progression-free survival (PFS) and risk of relapse. Patients receiving autologous transplantation had a significantly improved OS (P=0.006) and PFS (P=0.002) at 2 years with OS and PFS for autologous transplant 74% and 48%, respectively, compared with 51% and 28% for allogeneic transplantation. By 4 years after transplantation, outcome was similar with OS and PFS for autologous transplantation 41% and 23%, respectively, compared with 39% and 18% for allogeneic transplantation. The 4-year cumulative incidence of nonrelapse mortality was significantly higher in patients receiving allogeneic transplantation (24% vs 13%) (P=0.004). Relapse was the principle cause of treatment failure for both groups; however, there was a significantly reduced risk of relapse associated with allogeneic transplantation at 4 years: 46% for allograft vs 56% for autograft (P=0.02). Despite a lower risk of relapse after allogeneic transplantation, autologous transplantation is associated with improved OS and PFS compared with allogeneic transplantation in patients with MM. Strategies focused on reducing nonrelapse mortality in allogeneic transplantation may translate into an improved outcome for patients receiving allogeneic transplantation.     

Timing of autologous stem cell transplantation from last chemotherapy affects lymphocyte collection and survival in non-Hodgkin lymphoma

Autograft absolute lymphocyte count (A-ALC) is a prognostic factor for survival in non-Hodgkin lymphoma (NHL) after autologous stem cell transplantation (ASCT). An A-ALC is dependent upon the preaphaeresis absolute lymphocyte count (PA-ALC) at the time of aphaeresis. It was hypothesised that the time interval from last chemotherapy (TILC) to aphaeresis affects PA-ALC. One hundred and sixty consecutive NHL patients who underwent ASCT at the Mayo Clinic between 1996 and 2001 were evaluated. A strong correlation between TILC and PA-ALC (r = 0.67, P < 0.0001) was identified. Higher PA-ALC was observed in TILC > or =55 d compared with TILC <55 d [median: 7.0 vs. 3.8 x 10(9)/l], P < 0.0001). TILC as a continuous variable was identified as a prognostic factor for overall survival (OS) [hazard ratio (HR) = 0.989, P < 0.01] and progression-free survival (PFS) (HR = 0.992, P < 0.0492). Median OS and PFS were longer in the TILC > or =55 d vs. TILC <55 d group (not reached vs. 21 months, P < 0.0008; 76 vs. 9 months, P < 0.0025, respectively). Multivariate analysis demonstrated TILC to be an independent prognostic indicator for OS and PFS. These findings suggest that the immune status of the host at the time of aphaeresis may predict survival after ASCT.     

Outcomes of young adults (aged ≤ 40 years) with newly diagnosed multiple myeloma after up-front autologous stem cell transplant

Multiple myeloma (MM) primarily affects older patients. There are scarce data on the outcomes of young adults undergoing autologous transplantation (auto-HCT). In this single-centre analysis, we included 117 younger patients, with a median age of 37 years (range 22–40) at transplant. Seventeen (15%) patients had high-risk cytogenetics. Before transplant, 10% of patients achieved ≥CR and 44% achieved ≥VGPR. At best post-transplant response, 56% and 77% of patients achieved ≥CR and ≥VGPR respectively. With a median follow-up for survivors of 72.6 months (range 0.9–238.0), median PFS and OS were 43.1 months (95% CI 31.2–65.0) and 146.6 months (95% CI 100.0–208.1) respectively. Patients who underwent auto-HCT after 2010 had better median PFS (84.9 months vs. 28.2 months, p < 0.001) and OS (NR vs. 91.8 months, p < 0.001) compared with those transplanted earlier. In multi-variate analysis, achieving ≥CR as best post-transplant response was associated with improved PFS (HR [95% CI] 0.55 [0.32–0.95], p = 0.032), while achieving ≥VGPR was predictive of superior OS (0.32 [0.16–0.62], p < 0.001). Three patients (3%) developed a second primary malignancy. Younger MM patients had durable survival after auto-HCT, which further improved after the availability of novel anti-myeloma drugs in recent years. Depth of response following transplant remains a key predictor of survival.     

A retrospective analysis of outcomes for primary mediastinal large B-cell lymphoma treated with RCHOP followed by radiotherapy or front-line autologous stem cell transplantation

Objectives: Our aim was to retrospectively investigate the data from our institute the response rate and outcome in patients with primary mediastinal B-cell lymphoma (PMBL) who received the rituximab in combination with CHOP (RCHOP) followed by autologous stem cell transplantation (ASCT) or RCHOP followed by involved field radiation therapy (IFRT).

Methods: Sixty five patients with PMBL received RCHOP as first-line chemotherapy between January 2005 and December 2010. Forty of the 65 patients completed the planned subsequent IFRT after initial chemotherapy. Thirteen of the 65 patients received the front-line ASCT after RCHOP. Twelve patients received RCHOP alone.

Results: Thirty two of the 40 patients who received the RCHOP followed by IFRT have complete remission (CR) or CRu (CR/unconfirmed). All patients have CR or CRu after the ASCT. The progression free survival (PFS) and the estimated overall survival (OS) rate at 5 years for 32 CR/CRu patients in the RCHOP followed by IFRT group were 57 and 65%, respectively, as compared to RCHOP/ASCT group who were 94 and 100%, respectively. Twelve patients who received RCHOP alone had the same PFS and OS rate as the 40 patients who received RCHOP/IFRT (5-year PFS:62 vs. 65%, p?=?0.068; 5-year OS:57 vs. 67%, p?=?0.058). For all 65 patients, the age-adjusted international prognostic index (aaIPI) score remained the only predictor of a worse outcome.

Conclusion: The PFS and OS rate of RCHOP/IFRT were found to be unsatisfied. RCHOP/ASCT showed a satisfactory PFS and OS rate.     

Tandem transplants with different high-dose regimens improve the complete remission rates in multiple myeloma. Results of a Grupo Español de Síndromes Linfoproliferativos/Trasplante Autólogo de Médula Osea phase II trial

Between 1994 and 1999, 88 multiple myeloma (MM) patients were included in a phase II study to evaluate a tandem autologous stem cell transplantation (ASCT) programme. The first was conditioned with melphalan 200 mg/m2 (MEL200-ASCT1), and the second with cyclophosphamide, etoposide and BCNU (CBV-ASCT2). All patients were in response after MEL200-ASCT1. A control group of MM patients with response to a single ASCT was selected to compare outcomes. After MEL200-ASCT1, 26 patients (30%) achieved complete remission (CR). Of the remaining 48 evaluable patients, 16 (33%) achieved CR with CBV-ASCT2. The final CR rate was 48%. The 5-year survival (OS) was 55%[95% confidence interval (CI) 43-67%] while the event-free survival (EFS) was 28% (95% CI 15-39%). CR status after CBV-ASCT2 was the most important prognostic factor for OS and EFS (P = 0.00001), although no differences in outcomes were detected when the patients in CR after MEL200-ASCT1 were compared with those who obtained CR after CBV-ASCT2. Univariate and multivariate analyses showed improved OS and EFS for the tandem series as compared with the control series treated with a single MEL200-ASCT. However, in a stratified comparison by response, there were no prognostic differences between tandem patients and control patients treated with a single ASCT. In summary, our study suggests that the benefit of a second high-dose therapy course depends on its capacity to result in CR for MM patients who have not attained CR after ASCT1.