Non‐myeloablative conditioning and allogeneic transplantation for multiple myeloma

In multiple myeloma (MM), allogeneic stem cell transplantation (alloHCT) carries a lower relapse risk than autologous transplantation but a greater transplant‐related mortality. Nonmyeloablative conditioning for allogeneic transplantation (NST) reduces transplant‐related toxicity. Results are encouraging when used during first remission in low‐risk patients, but less‐so in relapsed or refractory disease. This is a single‐center retrospective analysis of 20 previously treated MM patients who underwent NST from matched‐related or matched‐unrelated donors from 2000–2006. Median age was 52.7 years (37.2–68.0). Twenty‐five percent had advanced or high‐risk disease. Eleven still had active disease prior to NST. Conditioning was total body irradiation 200 cGy on a single fraction on day ?5, followed by antithymocyte globulin (ATG) 1.5 mg/kg/day and fludarabine 30 mg/m²/day on days ?4 to ?2. All received immunosuppression, most commonly with oral mycofenylate mofetil and cyclosporine beginning on day ?5. At day 100, 50% had achieved complete remission. Transplant‐related mortality was 25%. Median overall survival (OS) was 21.2 months (0.6–90+) and progression‐free survival (PFS) 6.6 months (0.6–90+). Both OS and PFS were 24% at 3 years. OS was significantly greater for patients with age <52 years (median 27 months vs. 7.9 months, P = 0.031), and there was a trend toward greater OS for those with β2 microglobulin <2.5 mg/l (median 27 months vs. 7.7 months, P = 0.08). Donor characteristics and Ig type had no significant effect on survival. These data suggest a benefit of NST in relapsed/refractory MM. Randomized trials must be performed to confirm and further qualify this benefit. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

Tacrolimus as monotherapy or combined with minidose methotrexate for graft-versus-host disease prophylaxis after allogeneic peripheral blood stem cell transplantation: long-term outcomes

We report long-term outcomes for allogeneic peripheral blood stem cell (PBSC) recipients, evaluating cumulative incidence (CI) of acute and chronic graft-versus-host disease (GVHD), after use of tacrolimus with or without minidose methotrexate for GVHD prophylaxis. From April 1996 to April 1998, 97 adults underwent allogeneic PBSC transplantation. The first 49 received tacrolimus monotherapy as GVHD prophylaxis and the subsequent 48 received combination therapy. The median follow-up for survivors was 67 months. Compared to combination therapy, tacrolimus monotherapy resulted in enhanced neutrophil engraftment, shortened hospitalization, comparable rates of GVHD, and equivalent 100-day survival. The CI of grades II-IV acute GVHD was 35% with tacrolimus and 23% with the combination (P=0.19). The CI of III-IV GVHD was 22% for tacrolimus and 19% for the combination. CI of chronic GVHD was similar between the two groups (P=0.5). Patients with good-risk disease had superior overall survival (OS) when compared to those with poor-risk features (P<0.001). Within the good-risk disease category, patients receiving methotrexate had a trend towards improved OS (P=0.07). Multivariate analysis indicated good-risk disease status and methotrexate were independently associated with improved OS, progression-free survival (PFS), and relapse. In addition, patients developing chronic GVHD had a significantly reduced risk of relapse and improved PFS.     

An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation

The role of allogeneic bone marrow transplantation in lymphoma remains uncertain. We have analyzed 1185 allogeneic transplants for lymphoma reported to the EBMT registry between 1982 and 1998 and compared the results with those of 14687 autologous procedures performed over the same period. Patients receiving allogeneic transplants were subdivided according to histology: low-grade non-Hodgkin's lymphoma (NHL) 231 patients; intermediate-grade NHL 147 patients; high-grade NHL 255 patients; lymphoblastic NHL 314 patients; Burkitt's lymphoma 71 patients; and Hodgkin's disease 167 patients. These patients received allogeneic transplants as their first transplant procedure. Actuarial overall survival (OS) at 4 years from transplantation was: low-grade NHL 51.1%; intermediate-grade NHL 38.3%; high-grade NHL 41.2%; lymphoblastic lymphoma 42.0% years; Burkitt's lymphoma 37.1%; and Hodgkin's disease 24.7% years. These outcomes are relatively poor because of the high procedure-related mortality associated with these procedures, particularly in patients with Hodgkin's disease (51.7% actuarial procedure-related mortality at 4 years). Multivariate analysis showed that for all lymphomas apart from Hodgkin's disease, status at transplantation significantly affected outcome. A matched analysis was performed: for all categories of lymphoma, OS was better for autologous than for allogeneic transplantation. Relapse rate was better in the allogeneic group for low-, intermediate- and high-grade, and lymphoblastic NHL. It was equivalent for Burkitt's lymphoma and worse in the allogeneic group for Hodgkin's disease. Allogeneic transplantation appears to be superior to autologous procedures in terms of producing a lower relapse rate. The toxicity of allogeneic procedures must however be reduced before this translates into an improvement in OS.     

Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome

Risk-adapted treatment of multiple myeloma (MM) includes autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (HSCT). Case reports on extramedullary (EM) compared to bone marrow (BM) relapse after HSCT suggest a dismal prognosis. We compared the outcome of 78 MM patients relapsing after auto- (group A: n = 53) or allo- (group B: n = 25) HSCT, stratified into BM (64 patients) vs EM (14 patients) relapse. The relapse-specific groups were also compared with respect to risk factors, including age, beta2-microglobulin, pretreatment, cytogenetics and stage. EM relapse sites were lungs (5), soft tissue (4), pericardium (2), bone (1), skin (1) and CNS (1). As of May 2004, the overall (OS) and progression-free (PFS) survival after HSCT in patients relapsing from EM sites was not significantly different from BM relapse patients, both after auto- and allo-HSCT. Although MM patients relapsing from EM sites after allo-HSCT used to be regarded as having few therapeutic options, we observed encouraging responses to donor lymphocyte infusions (DLI). Treatment responses to DLIs were observed in 5/9 (56%) BM relapse patients, and in 3/4 (75%) EM relapse patients. These observations suggest that EM relapse after HSCT is common and needs an individualized diagnostic and therapeutic approach in MM during clinical follow-up after HSCT.     

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.     

Thalidomide plus dexamethasone is an effective salvage regimen for myeloma patients relapsing after autologous transplant

OBJECTIVES: High-dose therapy followed by autologous transplant (AT) is the effective induction treatment for newly diagnosed multiple myeloma (MM) patients. The best salvage therapy has not been defined; treatment options include thalidomide plus dexamethasone (TD), AT and conventional chemotherapy (CC). The aim of the study was to define the best treatment option for patients relapsing after AT. PATIENTS AND METHODS: We compared the outcome of 90 MM patients treated at diagnosis with AT and then salvaged with TD (43 patients), AT (28 patients) or CC (19 patients). The major prognostic factors, the median times between diagnosis and start of salvage treatment and the progression-free survival (PFS) from diagnosis were similar among the three groups. RESULTS: The response rate was higher after salvage AT and after TD, and lower after CC (P < 0.001). TD significantly prolonged PFS from first relapse (P < 0.0001). Median PFS was 20.3 months after TD, 9 months after AT, and 4.5 months after CC. Overall survival (OS) from first relapse was significantly improved by TD (median OS 55.5 months) but not by AT (15 months) or CC (27.5 months) (P = 0.008). Multivariate analysis indicated that TD and age were the only independent risk factors associated with improved outcome. CONCLUSION: TD improved PFS and OS in myeloma patients relapsing after AT.     

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 role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis

Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.     

The role of high-dose therapy and stem cell rescue in the management of T-cell malignant lymphomas: a BSBMT and ABMTRR study

Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous subset of lymphomas with a poorer prognosis compared with B-cell lymphomas. We conducted a retrospective study of 82 patients who received high-dose therapy for PTCL (autologous SCT (ASCT) N=64; allogeneic SCT (Allo-SCT) N=18). With a median follow-up from ASCT of 37 months from transplant, 33 patients were alive; 20 died of progressive disease, 10 died from non-relapse mortality (NRM) with 1 unknown cause. Three-year overall survival (OS) and progression-free survival (PFS) were 53% (95% confidence interval (CI) 42, 67) and 50% (95% CI 39, 64), respectively. Factors significantly affecting OS and PFS on univariate analysis were histological subtype and chemotherapy sensitivity. In a multivariate analysis, the only factor with significant impact was chemotherapy sensitivity. After a median follow-up from Allo-SCT of 57 months, five patients were alive; five died of progressive disease and eight died from NRM. The 3-year OS and PFS were 39% (95% CI 22, 69) and 33% (95% CI 17, 64), respectively, and the 3-year relapse rate was 28% (95% CI 6, 50). These results demonstrate that high-dose chemotherapy with autologous stem cell rescue has a substantial role in the management of T-cell lymphoma. The use of full-intensity allogeneic transplantation is limited by high transplant-related mortality, and exploration of reduced intensity regimens is warranted.     

Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: a multicentre experience

Patients with relapsed diffuse large B-cell lymphoma (DLBCL) who have failed or are ineligible for autologous haematopoietic cell transplantation (HCT) have a poor prognosis. We examined the outcomes of non-myeloablative allogeneic HCT in this setting. Thirty-one patients with DLBCL and one patient with Burkitt lymphoma received allogeneic HCT following 2 Gy total body irradiation with or without fludarabine. Median age was 52 years. Twenty-four patients (75%) had undergone prior autologous HCT. Disease status at HCT was complete response (14/32, 44%), partial response (9/32, 28%), or refractory (9/32, 28%). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II-IV, grades III-IV, and chronic GVHD were 53%, 19%, and 47% respectively. With a median follow-up of 45 months, 3-year estimated overall (OS) and progression-free survival (PFS) was 45% and 35% respectively. Three-year cumulative incidences of relapse and non-relapse mortality were 41% and 25% respectively. In multivariate models, chemosensitive disease and receipt of >or=4 lines of treatment before HCT were associated with better OS. Patients with chemosensitive disease had 3-year OS and PFS of 56% and 43% respectively. Non-myeloablative allogeneic HCT can produce long-term disease-free survival in patients with chemosensitive relapsed DLBCL who have failed or are ineligible for autologous HCT.     

Comparison of outcome following allogeneic bone marrow transplantation with cyclophosphamide-total body irradiation versus busulphan-cyclophosphamide conditioning regimens for acute myelogenous leukaemia in first remission

We evaluated transplant-related mortality (TRM), leukaemia relapse, leukaemia-free survival (LFS) and overall survival (OS) in patients receiving busulphan and cyclophosphamide (BuCy) or cyclophosphamide and total body irradiation (CyTBI) prior to allogeneic bone marrow transplantation (BMT) for acute myelogenous leukaemia (AML) in first remission. Outcomes of 381 human leucocyte antigen (HLA)-matched sibling transplants using BuCy were compared with 200 transplants using CyTBI performed between 1988 and 1996. The incidence of hepatic veno-occlusive disease was higher with BuCy (13%) than with CyTBI (6%) (P = 0.009). Risks of acute and chronic GVHD were similar. In multivariate analysis, relapse risk was higher in the BuCy group [relative risk (RR) = 1.72; 95% confidence interval (CI), 1.05-2.81; P = 0.031]. Eleven of 373 evaluable patients in the BuCy group had a central nervous system relapse in contrast to none of 194 evaluable patients in the CyTBI group (P = 0.016). There were no differences in TRM, LFS and OS. CyTBI conditioning may lower relapse risk but produces comparable TRM, LFS and OS to BuCy for HLA-matched sibling transplantation in first remission AML.     

Myeloablative allografting for chronic lymphocytic leukemia: evidence for a potent graft-versus-leukemia effect associated with graft-versus-host disease

In all, 30 patients with CLL proceeded to myeloablative allogeneic BMT using related (n=20, 67%) or unrelated (n=10) donors, at the Princess Margaret Hospital (Toronto) (n=20) or the Leukemia/BMT Program of BC (Vancouver) (n=10), from 1989 to 2001. Median (range) interval from diagnosis to BMT was 4.8 (0.3-13) years, median number of prior therapies was three and median age 48 years. The preparative regimen included total body irradiation in 15 (50%). In all, 14 of 30 patients (47%) are alive, with median (range) follow up of 4.3 (2.4-10.5) years. All are in complete remission, two following therapy for post-BMT progression. Actuarial overall (OS) and event-free survival (EFS) at 5 years is 39% (OS 48% for related donor and 20% for unrelated donor BMT); cumulative incidence of nonrelapse mortality (NRM) and relapse is 47 and 19%, respectively. Both acute (RR=0.008, P=0.01) and chronic (RR=0.006, P=0.02) Graft-versus-host disease (GVHD) were associated with markedly decreased risk of relapse. Patients receiving grafts from unrelated donors had increased NRM (RR=3.6, P=0.02) and decreased OS (RR of death=3.4, P=0.002). Allogeneic BMT has resulted in long-term EFS in approximately 40% of patients with CLL. There is evidence for a strong graft-versus-leukemia effect associated with acute and chronic GVHD, resulting in near complete protection from relapse.     

Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p

In patients with multiple myeloma (MM), risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches. In the present study, we analyzed the prognostic value of 12 chromosomal abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial. Because of the 2-arm design of the study, we were able to analyze the effect of a bortezomib-based treatment before and after autologous stem cell transplantation (arm B) compared with standard treatment without bortezomib (arm A). For allanalyzed chromosomal aberrations, progression-free survival (PFS) and overall survival (OS) were at least equal or superior in the bortezomib arm compared with the standard arm. Strikingly, patients with del(17p13) benefited the most from the bortezomib-containing treatment: the median PFS in arm A was 12.0 months and in arm B it was 26.2 months (P = .024); the 3 year-OS for arm A was 17% and for arm B it was 69% (P = .028). After multivariate analysis, del(17p13) was an independent predictor for PFS (P < .0001) and OS (P < .0001) in arm A, whereas no statistically significant effect on PFS (P = .28) or OS (P = .12) was seen in arm B. In conclusion, the adverse impact of del(17p13) on PFS and OS could be significantly reduced by bortezomib-based treatment, suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13).     

Autologous and allogeneic stem cell transplantation in adult ALL: the Swedish Adult ALL Group experience

Adult patients with acute lymphoblastic leukaemia (ALL) have been treated according to national protocols in Sweden since 1986. Stem cell transplantation (SCT) has been recommended in first remission for patients with risk factors for relapse, and for standard risk patients only after relapse. In this retrospective study, the results of autologous and allogeneic SCT in these populations were evaluated. In total, 187 patients with a median age of 34 years (17-66 years) underwent SCT. The 5-year disease-free survival (DFS), for all patients, was 26% (Confidence intervals (CI) 20-32%). The 5-year DFS was higher for patients transplanted in first remission 32% (CI 24-40%) compared to 14% (CI 5-23%; P<0.0001) in patients transplanted beyond first remission. No significant differences in DFS (P=0.06) were determined between autologous, related donor and unrelated donor SCT in the whole cohort. A lower relapse rate was counterbalanced by higher treatment-related mortality in patients undergoing allogeneic SCT. In Philadelphia-positive ALL, allogeneic SCT was superior to autologous SCT, with a 5-year DFS of 30% (CI 12-47%) vs 0% (P=0.04). Limited chronic graft-versus-host-disease (GVHD) was associated with an improved DFS of 53% (CI 38-69%) compared to no chronic GVHD of 22% (CI 10-36%; P=0.0008), indicating a clinically important graft-versus-leukaemia effect.     

Allogeneic or autologous stem cell transplantation (SCT) for relapsed and refractory Hodgkin's disease and non-Hodgkin's lymphoma: a single-centre experience

PURPOSE OF THE STUDY: The aim of the study was to evaluate which patient might benefit most from allogeneic stem cell transplantation (SCT) in the treatment of relapsed and/or refractory lymphoma. PATIENTS AND METHODS: Thirty-eight consecutive lymphoma patients receiving either autologous (n = 24) or allogeneic (n = 14) stem cell grafts at our institution from 1986 to 1998 were retrospectively analysed regarding overall survival (OS), disease-free survival (DFS), transplant-related mortality (TRM), and relapse incidence (RI). Uni- and multivariate analyses were performed to identify patient characteristics predictive for outcome after SCT. RESULTS: The probabilities of OS, DFS, TRM, and relapse were 57%, 51%, 29%, and 30% following autologous and 43%, 43%, 29%, and 38% following allogeneic SCT. Disease status (sensitive versus refractory) and the time interval between diagnosis and SCT were the most powerful predictive parameters for OS and TRM, whereas elevated serum LDH levels were signifcant in determining relapse. CONCLUSIONS: In patients with elevated serum LDH levels and bone marrow involvement at the time of transplantation allogeneic was superior to autologous SCT and resulted in better outcome due to a lower relapse incidence strongly suggesting the existence of a graft-versus-lymphoma effect.     

Hematopoietic stem cell transplantation in Lebanon: first comprehensive report

Hematopoietic SCT (HSCT) has become a curative therapeutic strategy for several malignant and nonmalignant diseases. We report the comprehensive results of the first 10 years of experience in HSCT from the two major BMT units in Lebanon: Makassed University Hospital and the American University of Beirut Medical Center. The median and the 5-year overall survival (OS) were 97 months and 58%, respectively, for the 84 patients who received allogeneic HSCT, and 60 months and 50%, respectively, for the 228 patients who received autologous BMT. The results for myeloablative allogeneic transplantation were as follows: AML (n=28, 5-year OS 58%, 5-year disease-free survival (DFS) 48%), CML (n=9, 5-year OS 66%, 5-year DFS 52%), ALL (n=13, 2-year OS 10%, 2-year DFS 10%), thalassemia (n=10, 5-year transfusion-free survival 67%). The results for autologous HSCT were as follows: diffuse large B-cell lymphoma (DLBCL) in relapse (n=37, 5-year OS 68%, 5-year progression-free survival (PFS) 65%), Hodgkin's lymphoma (n=55, 5-year OS 55%, 5-year PFS 36%), and first-line multiple myeloma (n=71, 5-year OS 53%, 5-year PFS 24%). For allogeneic transplanted patients, the cumulative TRM was 23% and the incidence of acute GVHD was 23%. For autografted patients, TRM was 2.6%. These results indicate that despite the relatively low socioeconomic status of the Lebanese population, both allogeneic and autologous HSCT are feasible with outcomes similar to developed countries.     

Prognostic factors for survival after autologous transplantation: a single centre experience in 133 multiple myeloma patients

Autologous stem cell transplantation (ASCT) has an established role in the treatment of symptomatic multiple myeloma (MM). Our aim was to analyse the impact of selected prognostic parameters on the survival of patients with MM after ASCT. The new International Staging System (ISS) was also evaluated. A total of 133 MM patients were transplanted in our centre between 1995 and 2002. Following ASCT, 35% of patients were in complete remission (CR) and 60% were in partial remission (PR). The median progression-free (PFS) and overall (OS) survival from transplantation were 29.5 and 68.8 months, respectively. Transplant-related mortality (TRM) was 3%. On multivariate analysis, factors associated with significantly shorter OS were lack of CR after transplant (P = 0.002, hazard ratio (HR): 3.1), stage 3 according to ISS (P = 0.001, HR: 3.0) and age at transplant over 60 years (P = 0.035, HR: 2.0). The status of disease before ASCT did not significantly affect PFS and OS after transplantation. We conclude that ASCT is a safe and effective procedure in MM patients, associated with low TRM. The survival after ASCT was dependent on response after ASCT, stage according to ISS and age.     

Effect of rituximab on peripheral blood stem cell mobilization and engraftment kinetics in non-Hodgkin's lymphoma patients

Rituximab is used for in vivo tumor cell purging for non-Hodgkin's lymphoma (NHL) patients prior to autologous peripheral blood stem cell transplantation (PBSCT). However, its effects on PBSC mobilization and function are poorly understood. We compared the mobilization characteristics and engraftment kinetics of 13 NHL patients receiving and 34 NHL patients not receiving rituximab 6 months before PBSC mobilization. In the rituximab group, there was a significantly longer time to neutrophil engraftment (P=0.0466), a trend toward the need for BM harvest to supplement low-yield PBSC collections (31 vs 9%, P=0.08) and a significantly increased rate of bacteremia episodes (62 vs 26%, P=0.025). Median progression-free survival (PFS) and overall survival (OS) were significantly longer in the rituximab compared to the nonrituximab patients (P=0.049 and 0.042, respectively). However, patients in the nonrituximab group were at high risk for recurrence and expected to have shorter survival. Rituximab used within 6 months prior to collection may have a detrimental effect on PBSC mobilization and engraftment. However, rituximab is a major therapeutic breakthrough for NHL treatment and this negative effect may be offset by improved survival. Further studies are warranted in larger populations to determine the impact of rituximab on engraftment, PFS and OS.     

Syngeneic transplantation in multiple myeloma - a case-matched comparison with autologous and allogeneic transplantation. European Group for Blood and Marrow Transplantation.

Twenty-five patients with multiple myeloma received bone marrow grafts (n = 24) or peripheral blood stem cells (n = 1) from twin donors. The outcome was compared in a case-matched analysis to 125 patients who underwent autologous transplantation, and 125 who underwent allogeneic transplantation. Seventeen patients (68%) receiving twin transplants entered complete remission, which was not significantly different from that of autologous (48%) or allogeneic (58%) transplants. The median overall and progression-free survival for the twins was 73 and 72 months, respectively. The overall survival tended to be better (73 vs 44 months) and the progression-free survival was significantly better (72 vs 25 months) than with autologous transplantation and both were significantly better than with allogeneic transplantation. Three of 17 patients who entered complete remission following transplantation had relapsed at follow-up. This relapse rate was significantly lower than following autologous transplantation and similar to the relapse rate with allogeneic transplantation. Only two twins died of transplant-related toxicity. Six further patients died of progressive or relapsing disease. Syngeneic transplantation in multiple myeloma appears to be the treatment of choice if a twin donor is available. A lower relapse risk than in autotransplantation may be due to reinfusion of malignant cells in some patients treated with this modality or to the presence of a graft-versus-myeloma effect in some syngeneic transplants.     

Allogeneic hematopoietic stem cell transplantation in patients with diffuse large B cell lymphoma relapsed after autologous stem cell transplantation: A GITMO study

Patients who relapse after an autologous hematopoietic stem cell transplantation (SCT) have a very poor prognosis. We have retrospectively analyzed diffuse large B cell lymphoma patients who underwent an allo-SCT after an auto-SCT relapse reported in the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) database. From 1995 to 2008, 3449 autologous transplants were reported in the GITMO database. Eight hundred eighty-four patients relapsed or progressed after transplant; 165 patients, 19% of the relapsed patients, were treated with allo-transplant. The stem cell donor was related to the patient in 108 cases. A reduced intensity conditioning regimen was used in 116. After allo-SCT, 72 patients (43%) obtained a complete response and 9 obtained a partial response with an overall response rate of 49%; 84 patients (51%) experienced rapid progression of disease. Ninety-one patients died, 45 due to disease and 46 due to treatment-related mortality. Acute graft-versus-host disease was recorded in 57 patients and a chronic GvHD in 38 patients. With a median follow-up of 24 months (2-144) after allo, overall survival (OS) was 39%, and after a median of 21 months (2-138) after allo, progression-free survival (PFS) was 32%. Multivariate analysis indicated that the only factors affecting OS were status at allo-SCT, and those affecting PFS were status at allo-SCT and stem cell donor. This retrospective analysis shows that about one-fifth of patients with diffuse large B cell lymphoma who experience relapse after autologous transplantation may be treated with allogeneic transplantation. Moreover, the only parameter affecting either OS or PFS was the response status at the time of allo-SCT.