Reduced-intensity Allogeneic Hematopoietic Stem Cell Research Articles

Assessment Of The Hematopoietic Cell Transplantation Comorbidity Index In Older Patients Receiving Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is an established therapy for malignant and nonmalignant hematologic disorders. Reduced-intensity conditioning (RIC) regimens have expanded the use of HSCT to elderly and higher risk patients. However, HSCT still remains associated with a significant mortality and morbidity and the careful assessment of risks and benefits before transplantation is essential. Major factors which influence non-relapse mortality (NRM) and overall survival (OS) after HSCT are diagnosis, type of transplant, remission status and the patient's risk profile, which includes age and presence of comorbidities. The use of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) has been proposed to predict the probability of NRM and OS following HSCT. However, the HCT-CI usefulness for older patients receiving a reduced intensity allogeneic HSCT remains unclear. MethodsA retrospective medical record review was performed to collect data from patients who underwent an allogeneic HSCT at a large, urban, NCI Comprehensive Cancer Center during a five year period (January 2005 to December 2010). Patients 55 years and older who were transplanted using RIC for a hematologic malignancy were selected to be analyzed. Comorbidities and test results were collected to determine the HCT-CI score and other clinical data collected included disease and remission status at time of transplant. Results85 patients aged >55 years old who received a RIC HSCT for hematologic malignancies between January 2005 to December 2010 were analyzed. The median patient age at the time of transplantation was 63 years (range: 55-75 years). The patient diagnoses included AML (39%), NHL (29%), MM (9%), MDS (11%), CLL (8%), ALL (4%). The median pre-transplantation HSCT-CI score was 2 (range: 0-9). Among 85 patients, OS at 2 years was 44%. The 2 yr OS was 31%, 37% and 44% in the low-, intermediate-, and high-risk HSCT-CI groups (p = 0.61), respectively. The corresponding NRM at 2 years was 25%, 17% and 18% (p = 0.91). We found no predictive value of HSCT-CI for either OS or NRM in older patients having an allogeneic HSCT with reduced-intensity condition. Stratification of age (55-59, 60-64, and 65+) showed no significant impact on 2 yr OS or NRM. However, there was a trend towards a better 2 yr OS for patients who had achieved a CR versus no CR at time of transplant (48% vs 41%). ConclusionOlder patients with hematologic malignancies represent a highly selected cohort, with the prospect of an allogeneic HSCT often considered too high-risk. A method to reliably stratify these older HSCT candidates is greatly needed. However, the HCT-CI score in this retrospective analysis did not help predict their NRM or 2 year OS for patients 55 years and older with hematologic malignancies receiving a reduced intensity HSCT. Further research is warranted into what combination of factors may provide a reliable predictive score for older patients with hematologic malignancies. Disclosures:Mehta:Millennium: Speakers Bureau; Celgene: Speakers Bureau.

Correction: Allogeneic hematopoietic stem cell transplantation for relapsed acute myeloid leukemia in ETO positive with reduced-intensity conditioning.

[This corrects the article DOI: 10.18632/oncotarget.22612.].

Cytomegalovirus Status and the Outcome of T Cell–Replete Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation

Cytomegalovirus (CMV) serostatus of donor and recipient are frequently used in algorithms of donor selection, whereas the impact of CMV reactivation on transplantation-related mortality, leukemia control, and overall survival (OS) remains controversial. Therefore, we retrospectively studied the impact of latent or active CMV infections on the outcome and occurrence of graft-versus-host disease (GVHD) after reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (SCT) in 294 patients during the period from 2004 to 2010. CMV viral load was routinely monitored in plasma using a quantitative PCR. Preemptive antiviral therapy was initiated when the viral load in plasma exceeded a predefined threshold. In a proportional hazards model, a seropositive recipient was significantly associated with increased occurrence of acute GVHD. However the CMV serostatus of both recipient and donor and the presence of active CMV infection was not associated with the occurrence of relapses, chronic GVHD, or OS. We conclude that in the presence of viral load monitoring and preemptive treatment, latent or active CMV infection does not substantially affect the OS after T cell–replete RIC allogeneic SCT.

Research progress of reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in treatment of myelodysplastic syndrome

Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is likely to be the optimum method to cure international prognostic scoring system (IPSS) intermediate and high-risk patients with myelodysplastic syndrome(MDS). However, patients suffered with MDS are usually too old to undergo myeloablative conditioning allogeneic stem cell transplantation(MAC-HSCT). On account of its advantages of higher efficiency and lower toxicity, reduced intensity conditioning allogeneic stem cell transplantation(RIC-HSCT) is widely applied in the treatment of MDS patients. Currently, fludarabine plus alkylating regimens are widely applied, but the clinical outcomes are different from each regimen. Although RIC-HSCT has unique advantages in treating intermediate and high-risk elder MDS compared with MAC-HSCT and non-HSCT therapy, whether the outcome is influenced by factors such as tumor burden, recipient age, IPSS risk stratification, type of allo-HSCT, and comorbidity before transplantation is still unclear. In this article, we review literatures on RIC-HSCT in treatment of MDS. Key words: Myelodysplastic syndrome; Transplantation conditioning; Hematopoietic stem cell transplantation

Outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma.

We retrospectively evaluated single-institute outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a reduced-intensity conditioning regimen consisting of fludarabine (125 mg/m²) and melphalan (140 mg/m²) for multiple myeloma. Twenty-three patients (median age: 46 years) were evaluated. Stem cell sources were bone marrow or peripheral blood stem cells from siblings (n = 4) and bone marrow from unrelated donors (n = 19). For graft-versus-host disease prophylaxis, cyclosporine A or tacrolimus with short-term methotrexate was given. Disease status at time of transplant was complete response in four patients, very good partial or partial response in 13, and stable or progressive disease in six. The median follow-up period of 7 survivors at analysis was 73.2 months (range 46.0-158.9 months). During the follow-up, disease recurrence or progression was observed in 21 patients, and was primary causes of death in 88% of the patients. The 5-year overall survival and progression-free survival rates were 38.6% (95% CI 19.3-57.7%) and 5.4% (95% CI 0.4-21.6%), respectively. Although allo-HSCT with this conditioning could be safely performed, further refinement of this approach aiming at more effective eradication of myeloma cells is clearly warranted.

Higher Tacrolimus Concentrations Early Post-Transplant Reduce the Risk of Acute Graft-Versus-Host Disease in Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation

s / Biol Blood Marrow Transplant 21 (2015) S355eS373 S369 be more economically responsible in a small group of patients will have a large impact on drug expenditures. As the price of thiotepa continues to rise and alternative regimens are utilized more frequently, there remains a responsibility for the practitioner to report and determine the most effective, safe, and economically responsible pediatric hematopoietic stem cell transplant conditioning regimen.

Impact of Serotherapy on Immune Reconstitution and Survival Outcomes after Stem Cell Transplantations in Children: Thymoglobulin Versus Alemtuzumab

Abstract The outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is strongly affected by the kinetics of reconstitution of the immune system. This study compared the effects of antithymocyte globulin (ATG) and alemtuzumab on various outcome parameters after HSCT. The study cohort consisted of 148 children, with a median age of 9.6 years (range, .4 to 19.0), who underwent HSCT for malignant and benign hematological disorders in a single HSCT unit. Conditioning included ATG (n = 110) or alemtuzumab (n = 38). Cox proportional hazard regression analysis showed that alemtuzumab significantly delayed the recovery of CD3+ T cells and CD4+as well as CD8+ T cell subsets (P ≤ .001) and natural killer (NK) cells (P = .008) compared with ATG. In both ATG- and alemtuzumab-treated patients, shorter drug exposure lead to significantly faster recovery of T cells. Alemtuzumab was associated with lower donor chimerism 3 and 6 months after transplantation and a higher risk of disease relapse (P = .001). The overall survival and event-free survival risks were significantly lower for alemtuzumab-treated patients (P = .020 and P

Encouraging Outcomes of Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Patients with Acute Lymphoblastic Leukemia in Second Complete Remission

[Background] We have been performing reduced-intensity stem cell transplantation (RIST) to avoid preconditioning-related complications. However, the effectiveness of RIST in pediatric patients with acute lymphoblastic leukemia (ALL) remains to be clarified.[Methods] We retrospectively reviewed 37 pediatric patients with ALL in second complete remission (CR2) who underwent first allogeneic hematopoietic stem cell transplantation (allo-SCT) between 1993 and 2012 in our institute. We compared the outcomes of RIST with those of myeloablative stem cell transplantation (MAST).[Results] The median age at allo-SCT was 9 years (range, 1 to 18 years). There were 33 B-lineage ALL, 3 T-lineage ALL, 1 lineage unknown ALL, and none of Philadelphia chromosome-positive ALL. Sixteen patients received HLA-matched bone marrow (7 related; 9 unrelated), 12 HLA-mismatched bone marrow (11 unrelated; 1 HLA haploidentical related), 4 cord blood, and 5 CD34 positive peripheral blood stem cells (HLA haploidentical related). In all patients, the 5-year overall survival (5y-OS) rate and the 5-year event free survival (5y-EFS) rate were 75.1% and 56.5%, respectively.Seven patients underwent RIST and 30 patients underwent MAST. The median follow-up durations of RIST and MAST groups were 3.3 years (range, 0.9 to 8.2 years) and 11.3 years (range, 0 to 21.2 years), respectively. The 5y-OS rates in RIST and MAST groups were 85.7% and 59.8%, and the 5y-EFS rates were 71.4% and 53.3%, respectively. The 5-year cumulative transplant-related mortality (TRM) rates in RIST and MAST groups were 0% and 31.0%, and the 5-year cumulative relapse rates were 28.6% and 24.3%, respectively.[Discussion] In our series, the cumulative relapse rate in RIST group was similar with that in MAST group, and the cumulative TRM rate in RIST group was lower than that of MAST group. Therefore, both of the 5y-OS and the 5y-EFS rates in RIST group seem to be better than those in MAST group. The outcomes of RIST in our series do not seem to be poorer. Although further studies are needed because of the small size of patients and short follow-up duration, RIST can be considered as the first transplantation for pediatric patients with ALL in CR2. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Imatinib Combined with Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Versus Imatinib Alone for Young Patients with Chronic Myeloid Leukemia in Chronic Phase

Background and AimsThe relative merits of reduced intensity hematopoietic stem cell transplantation (RIST) for chronic myeloid leukemia (CML) in the first chronic phase (CP) in the imatinib (IM) era have not previously been evaluated. This prospective clinical trial was designed to compare the medical outcomes, with combination therapy of RIST plus imatinib versus imatinib alone in treating young patients with first CP including the early CP (ECP; a CML duration < 12 months) and the late CP (LCP; a CML duration ∼12 months).Patients and methodsFrom January 2005 to January 2013, Patients aged ¡Ü 49 years, who were treated consecutively at the First Affiliated Hospital of Zhejiang University, were non-randomly assigned to treatment with imatinib alone or RIST group according to whether the patient had an HLA-matched donor; those with an HLA-matched donor were assigned to the RIST group, and the others were assigned to the imatinib group. In the RIST group, the conditioning regimen was based on busulfan, fludarabine and anti-thymocyte globulin, combined with pre-transplant imatinib for 3-12 months and post-transplant imatinib for 12 months.ResultsIn total, 130 patients with the age from 11 to 49 years old were recruited, 42 patients were assigned to the RIST group and 88 patients were assigned to the imatinib group, respectively. Based on an eight-year follow-up period, the overall survival (OS) and event-free survival (EFS) were comparable between RIST and IM group (8 year-OS: 85.5% vs 89.0%, p=0.186; 8 year-EFS: 78.2% vs 73.9%, p=0.59). Interval from diagnosis to imatinib treatment more than 12 months (Late CP), high socal score, and no complete cytogenetic response at 3 month to IM were the adverse prognostic factors for EFS and OS, but only the time from diagnosis to imatinib was an independent predictor after multivariate analysis (OS: estimated HR=5.8, P=0.009; PFS:estimated HR=4.7, P=0.01).Among the ECP patients, imatinib alone was superior to RIST, with 8-year EFS rates of 92.3% vs 83.4% (p=0.05) and OS rates of 96.6% vs. 90% (P=0.03), respectively. Among LCP patients, both treatments resulted in similar survival (8-year OS rate: 62.6% vs 64.8%, p=0.53), but more LCP patients in the imatinib alone group experienced events as defined for 8-year EFS rate of 25.6%, compared with those in RIST group, with 8-year EFS rate of 48% P=0.047).The outcome of RIST was also released in the study. Primary graft failure occurred in two patients. Eleven (26.2%) developed grade I–II aGVHD, and one (2.4%) developed grade III–IV aGVHD. cGVHD could be evaluated in 39 patients, of whom 13 (33.3%) developed limited cGVHD and only 4 (10.2%) developed extensive cGVHD. The 100-day treatment-related mortality (TRM), one-year TRM and 8-year TRM was 2.5%, 10% and 12.7%, respectively. The patients were treated with 12-month imatinib for relapse prophylaxis, and the 2-year relapse rate was 10.5%. There was no late relapse (relapse after two year post-transplantation ) case. The patients with higher EBMT risk scores (3-5) had an inferior survival than those with lower EBMT risk scores ( 69.2% vs 92.9%, P = 0.04), and the EBMT risk score was an independent risk factor for OS with an odds ratio of 5.1 in multivariate analysis.ConclusionsWe concluded that imatinib alone confers significant survival advantages for young patients with CML in the ECP. For those in the LCP, both treatment arms resulted in similar overall survival, but RIST plus IM group resulted superior EFS, compared with IM alone. Thus, imatinib is superior to transplantation as the first-line therapy for young patients in the ECP, as for LCP, RIST should be considered to combined with pre-transplant and post-transplant IM as the treatment choice, especially when the patient get low EBMT risk scores. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis

AbstractFrom 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n = 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n = 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar. Engraftment occurred in 97% of siblings and 76% of unrelated transplants, whereas secondary graft failure occurred in 3% and 12%, respectively. With a median follow-up of 25 months for patients alive, the overall survival (OS) was 75% in the sibling group (median not reached) and 32% in the unrelated group (median OS: 6 months, 95% confidence interval [CI]: 3, 25) (hazard ratio 3.9, 95% CI: 1.8,8.9) (P < .001). Nonrelapse mortality was 22% in sibling and 59% in unrelated AHSCT. Survival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2V617F status. In patients with MF with sibling donors, AHSCT is an effective therapy, whereas AHSCT from unrelated donors with FluMel/ATG conditioning led to a high rate of graft failure and limited survival. This trial was registered at www.clinicaltrials.gov as #NCT00572897.

Donor lymphocyte infusion is an effective therapy for relapsed Hodgkin lymphoma after reduced-intensity allogeneic hematopoietic stem cell transplantation

A 3-year-old boy with Hodgkin lymphoma relapsed only 2 months after completion of first-line therapy. He received reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation (RIC allo-HSCT), but relapsed again. To treat the second relapse, donor lymphocyte infusions were performed four times. He showed no evidence of disease and his quality of life was maintained for 500 days after stem cell transplant. However, his condition worsened and he died 3 years and 3 months after onset. In high-risk patients fully intolerant to myeloablative regimens, RIC allo-HSCT followed by subsequent donor lymphocyte infusions must be considered an effective therapeutic approach.

Relapsed Hodgkin lymphoma: management strategies.

Although Hodgkin lymphoma (HL) is largely curable with first-line therapy, approximately one-third of patients will not have a complete response to frontline treatment or will subsequently relapse. Only 50% of these patients will be effectively salvaged with conventional therapies. The prognosis is particularly poor for those patients with chemotherapy refractory disease, who are unable to obtain even transient disease control, and for patients who relapse following high dose chemotherapy and autologous stem cell transplant. In this review, we summarize the most recent updates on the management of patients with relapsed HL, the role of novel therapies such as brentuximab vedotin, and an overview of promising new agents currently under investigation. We also discuss the role of consolidation strategies such as high-dose chemotherapy and autologous stem cell transplant, and reduced-intensity allogeneic hematopoietic stem cell transplant, and the need for new strategies in the elderly patient population.

Long-Term Follow-Up Of Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation For High Risk Follicular Lymphoma

IntroductionFollicular lymphoma (FL) is the most frequent indolent lymphoma. Autologous hematopoietic stem cell transplantation (ASCT) allows durable progression-free survival in selected relapsed patients. Recently, the EBMT lymphoma working party has published the recommendations for ASCT and allogeneic hematopoietic transplantation (alloTPH) in FL. For those high-risk young patients relapsing after ASCT, alloTPH is a valid therapeutic option; the majority being done with reduced intensity conditioning (alloRIC). AimsOur aim is to describe the outcome of patients with FL who underwent an alloTPH in our cente. Factors potentially influencing outcome such us age, sex, FLIPI at diagnosis, disease status prior alloTPH, EBMT risk score, type of donor, graft vs host disease (GVHD) prophylaxis and development of GVHD were also analized. MethodsActuarial estimates of OS and PFS rates were calculated using the Kaplan-Meier method. OS was estimated from the date of transplantation to the date of death or last follow-up. PFS was defined as the time from transplantation until progression or death from any cause. PatientsWe retrospectively found 26 alloTPH in the period 1999 - 2013. Two alloTPH were conditioned with a myeloablative regimen. Patients who underwent an alloRIC (n=24) were all conditioned with Fludarabine 30 mg/m2/5 days and Melphalan 70 mg/m2/1 day. ResultsAlloTPH was from a matched related donor in 70.8% of cases, from a mismatched related donor in 4.2%, matched unrelated donor in 8.3% and from a mismatched unrelated donor in 16.7%.The median age was 49.5 years (range 35-61). The median time from diagnosis to alloTPH was 48 months (range 9 – 190), male: female ratio was 2:1. FLIPI at diagnosis was 0 in 16.7%, FLIPI 1 in 25%, FLIPI 2 in 33.3%, FLIPI 3 in 8.3% and FLIPI 4 in 16.7. Mean number of treatment pre alloTPH was 4.5 (range 2-6). Ten patients (41.7%) had previously received an ASTC.Response before alloTPH was complete response in 54.2%, partial response in 37.5% and stable disease in 8.4%. The majority of patients (95.8%) had an EBMT risk score higher than 3.Graft vs host disease prophylaxis consisted on cyclosporine + short course of methotrexate in 54.2%, cyclosporine + micophenolate in 41.7% and sirolimus + tacrolimus in 4.2%. In vivo T-cell depletion was done in 4 patients receiving grafts from a mismatched unrelated donor (ATG or alemtuzumab, 2 patients each).Mean CD34 cells/Kg infused was 6.45 x106/kg (range 1.92 – 15.6). The median time to granulocyte recovery (>0.5x109/L) was 15 days (range 11-19) and the median time to platelets recovery (>50x109/L) was 14 days (range 6-56).Acute GVHD was developed in 45.8% of patients; it was global grade 1-2 in 36.4% ,and grade 3-4 in 63.6%. Chronic GVHD was present in 58.3% of patients. The median time of chronic GVHD presentation was 196 days after alloTPH (range 101 – 569 days).Regarding opportunistic infections, 20.8% of patients reactivated CMV with no disease, 16.7% had intestinal disease due to CMV. Thirteen per cent of patients developed pulmonary fungal infection (i.e Aspergillus sp).With a median follow up of 48.50 months (range 0-161), the 5 years OS was 66.1% (CI 95% 43.76 - 88.44) and the 5 years PFS was 63.8% (CI 95% 43.22 - 84.4). Overall morbidity at 3, 6 and 12 months after alloTPH was 5%, 5% and 10.3% respectively. Only 1 patient relapsed at 38 months after alloTPH but is still alive. Causes of death were refractory GVHD (n=5), sepsis (n=3) and acute renal failure due to microangiopathy (n=1).Survival was influenced by GVHD prophylaxis. At the median time of follow up (48.50 months) patients receiving cyclosporine-methotrexate had an OS of 82.5% vs 30% for patients receiving cyclosporine-MMF (p<0.01).Other variables (FLIPI at diagnosis, sex, age older than 60 years, the EBMT risk score pre alloTPH and disease status) had no influence on survival. ConclusionsAlloTPH for high risk FL patients seems to overcome the negative effect of FL prognostic factors at diagnosis. This strategy shows an excellent disease control with a low transplant-related mortality. Disclosures:No relevant conflicts of interest to declare.

Follow Up On CD8-Depleted Donor-Lymphocyte Infusions After T-Cell Depleted Allogeneic Hemopoietic Stem Cell Transplantation

We applied prophylactic CD8-depleted (CD8depl) donor lymphocyte infusions (DLI) in the setting of T-cell depleted reduced-intensity allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. T-cell depletion was carried out by the use of high-dose Alemtuzumab (100 mg or 60 mg for unrelated or sibling donor transplantation, respectively). We have demonstrated the feasibility of this approach after having treated 23 patients in this protocol (Meyer et al. Blood 2007). From 2004 to 2011, 134 patients with different hematologic diseases were included and followed for a median observation time of 1.5 years after transplantation (range, 1.5-9 years). Median age was 56 years (range, 19-71). Stem cell source was peripheral blood from either matched siblings (n=23), matched unrelated (n=62), or donors with single HLA mismatches (unrelated n=48, related n=1). Tapering of cyclosporine A was started in the 6th week after transplantation. Subsequently, CD8depl DLI were administered prophylactically in escalating doses starting with 1x106 CD4 T cells/kg bodyweight. 53 patients received at least one dose of DLI. Among 81 patients who did not qualify for DLI, 60 patients had primary mild GVHD. Following DLI, acute GVHD was the major reason for withholding subsequent DLI-doses (66%), mainly because of acute GVHD ≤ 2°. Extensive chronic GVHD was diagnosed in 9.4% of the patients. Overall survival after 1 and 3 years was 60% and 43%, respectively. Survival significantly differed between the DLI and non DLI group after 3 years (63.8% vs. 30.1%, p=0.002). The inferior outcome of the non DLI group was confirmed when only those patients who did not receive DLI for other reasons than GVHD were considered (28.6%). The largest patient cohort in our trial were patients with AML and MDS (n=21 with and n=33 without DLI). In these patients, the survival benefit for the DLI group after 3 years was significant (75.8% vs 28.9%, p=0.0012). Interestingly, the relapse rate did not differ between DLI and non-DLI patients but the non-relapse mortality. The presence of GVHD at any time was associated with a reduced relapse rate (57.9% vs. 31.4%, p=0.0015), independent of DLI-application. However, GVHD had no impact on overall survival. Decreasing donor T-cell chimerism (TCC) was found in 34 patients who subsequently received DLI and 13 who did not. Following CD8depl DLI, 31 patients (88%) converted to full donor. In contrast, only 2 of the patients with decreasing TCC in the non-DLI group (15.3%) converted spontaneously. In summary, we observed that the application of prophylactic CD8depl DLI was associated with a survival benefit and the re-establishment of full donor T-cell chimerism. In AML/MDS patients the improved survival was associated with lower treatment-related mortality rather than a reduced relapse-rate. Our data strongly suggest randomized trials comparing prophylactic application of CD8depl DLI vs. no DLI as well as CD8depl vs. non-manipulated DLI in a preemptive setting. Disclosures: Off Label Use: MabCampath has been used for T-cell depletion.

TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial

AbstractThe purpose of this analysis was to provide 6-year follow-up of the CLL3X trial, which studied reduced-intensity allogeneic hematopoietic stem cell transplantation (HSCT) in patients with poor-risk chronic lymphocytic leukemia (CLL), and to investigate the effect of TP53, SF3B1, and NOTCH1 mutations on HSCT outcome. For 90 allografted patients, 6-year overall survival (OS) was 58% and 6-year event-free survival (EFS) was 38%. TP53, SF3B1, and NOTCH1 mutations were found in 30%, 26%, and 14% of the trial population, respectively. By univariate and multivariate analyses, the mutational status of the TP53, SF3B1, and NOTCH1 genes had no significant effect on OS and EFS. Studies of minimal residual disease confirmed durability of CLL eradication in mutated patients. We conclude that HSCT can provide long-term disease control in patients with poor-risk CLL independent of the presence of TP53, SF3B1, and NOTCH1 mutations. The trial has been registered at the US National Cancer Institute as #EU-20554, NCT00281983.

Spontaneous Subcapsular Splenic Hematoma Associated with Filgrastim in a Patient Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

To report the development of a spontaneous subcapsular splenic hematoma following filgrastim administration in a patient undergoing an allogeneic hematopoietic stem cell transplant. A 60-year-old female with myelodysplastic syndrome was admitted for a reduced-intensity allogeneic hematopoietic stem cell transplant from an unrelated donor. She received filgrastim 5 μg/kg starting on day 1 to accelerate neutrophil recovery. On day 5, she began reporting severe left chest-wall pain. Contrast-enhanced computed tomography of the abdomen/pelvis revealed a spontaneous subcapsular splenic hematoma. Upon discontinuation of filgrastim, the pain fully resolved. The patient was subsequently rechallenged with filgrastim, which led to recurrence of the left-sided chest-wall pain. Filgrastim was discontinued and the patient reported resolution of the pain. Filgrastim has been associated with splenic hematoma and splenic rupture, predominantly in healthy donors undergoing mobilization of peripheral blood stem cells. Although splenic rupture attributed to filgrastim in a patient undergoing allogeneic hematopoietic stem cell transplantation has been reported, to our knowledge, this is the first case report to establish causality. Using the Naranjo probability scale, an objective causality assessment revealed that the adverse drug event was highly probable. Although filgrastim-induced splenomegaly, splenic hematomas, and splenic rupture are rare, clinicians working in the bone marrow transplant setting should be cognizant of the potential of growth factors to cause these adverse events.

Clinical research of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma

This study was purposed to explore the efficacy and feasibility of reduced-intensity allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of multiple myeloma (MM). Three patients with MM from January 2011 to January 2012 in General Hospital of Beijing Military Area were treated by reduced-intensity allo-HSCT. All donors are compatriots and affinity HLA identical. Donors were mobilized with granulocyte colony-stimulating factor (G-CSF), the MM patients were given combined transplantation of bone marrow and peripheral blood stem cells. Preconditioning regimen consisted of fludarabine combined with melphalan and anti-human thymocyte globulin, and the classic cyclosporin A (CsA) combined with methotrexate (MTX) was used to prevent graft-versus-host disease (GVHD). The preventive donor peripheral blood stem cell infusion in dose 0.2×10(8)/kg mononuclear cells (MNC) was applied after 3 months of transplantation, then the toxicity, GVHD and disease-free survival (DFS) in patients were observed after transplantation. The results showed that 3 patients got hematopoietic reconstitution, the average time of neutrophils ≥ 0.5×10(9)/L and platelets ≥ 20×10(9)/L was 14.3 d and 15.3 d respectively, the detection of implanting efficacy displayed 100% complete donor hematopoiesis. Follow-up to January 2013, the median follow-up time was 13 months (12 to 15 months), As a result, none of the patients got GVHD, infection and other serious complications, all patients are still in complete remission (CR), the longest DFS time has reached to 15 months. It is concluded that the reduced-intensity allogeneic hematopoietic stem cell transplantation is the effective method for MM, this method has the high safety and efficacy, as well as high complete remission rate in early transplantation, the MM patients may get a long-term survival. This method can be used as a key technology in clinic for treating MM.

Assessment of the Hematopoietic Cell Transplantation Comorbidity Index in Patients Receiving Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation

s / Biol Blood Marrow Transplant 19 (2013) S279eS312 S290 Introduction: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is indicated for patients with intermediate or high risk primary Myelofibrosis (MF), and also in patients with Policitemia Vera or Essential Thrombocythemia who have progressed to high risk MF. The results for allogeneic HSCT with myeloablative conditioning seem to be better for patients younger than 45 years, determining lower relapse risk. However, Reduced Intensity Conditioning (RIC) for patients between 45 and 65 years-old has shown to be a promising strategy, with less mortality related to the procedure. This study aims describing a series of patients diagnosed with myelofibrosis, transplanted in the Hospital de Clinicas (HC) from the Federal University of Parana and Hospital Nossa Senhora das Gracas (HNSG) (Curitiba, Brazil). Patients and Methods: From 1984 to 2011, fourteen patients with MF were submitted to HSCT, eleven from the HC and three from HNSG. The median of age was 42 years (10-51). Therewere ten males and four females. In average, five blood transfusions were done per patient (0-61). Five male patients received the graft from a female donor, and two patients received an unrelated HSCT. The median of duration of the disease was 20 months (2-150). According to Dupriez Classification, all the patients were of intermediate and high risk. Five patients had a myeloablative conditioning (Busulfan plus Cyclophosphamide: 4; Cyclophosphamide plus Total Body Irradiation:1) while nine had a RIC transplant (Fludarabine 150mg/m2 plus Melphalan 140mg/m2:6; Fludarabine plus Melphalan plus Antithymocyte Globulin:2; Fludarabine 180mg/m2 plus Bulsufan 10mg/m2 plus Antithymocyte globulin 5mg/kg:1). Results: In the myeloablative conditioning group (n1⁄45), all the patients presented marrow engraftment; one relapsed. Three patients presented grade II-IV acute graft versus host disease, and four developed severe chronic graft versus host disease. Four patients died, and the only survivor was 10 years-old. Median survival was 479 days. In RIC group (n1⁄49), engraftment didn't occur in one patient (which had splenomegaly of 18 cm at the time of transplantation), and another three relapsed. The other seven patients remained alive and free of disease, with median survival of 750 days (34-1872; P1⁄4 0,000123). Conclusion: In spite of the limited number of patients in this study, data suggest that RIC regimens improved survival in HSCT for myelofibrosis in our center, even with a slightely greater relapse risk. Except for very young patients, this strategy should be considered for further investigation.

Graft-versus-Host Disease: State of the Science

Despite concerted research efforts, prevention and treatment of graft-versus-host disease (GVHD) have not changed significantly over the past 3 decades. The goal of this session is to provide an outline of the current state of the science with respect to the prevention, treatment, and evaluation of acute and chronic GVHD. In addition, we detail those strategies most likely to be at the forefront of clinical research in the upcoming years.

Editorial Commentary: Adenovirus Viremia and Infection After Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplant: Should We Institute a Routine Screening Program?

Editorial Commentary: Adenovirus Viremia and Infection After Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplant: Should We Institute a Routine Screening Program?