Use Of Reduced-intensity Conditioning Regimens Research Articles

Outcomes of a Novel Rituximab-Based Non-Ablative Conditioning Regimen for Hematopoietic Cell Transplantation in Severe Aplastic Anemia

IntroductionOlder patients with severe aplastic anemia (SAA) needing hematopoietic cell transplantation (HCT) typically require utilization of reduced intensity conditioning (RIC) regimens; however, use of RIC regimens in this population is limited by graft failure and transplant-related mortality due to toxicity and infections, particularly reactivation of Epstein-Barr virus (EBV). Novel RIC regimens with improved efficacy and decreased toxicity and risk of infectious complications are urgently needed to improve post-HCT outcomes for SAA patients.Patients and MethodsUtilizing institutional registries, we identified all SAA patients who underwent first allogeneic HCT using an FCR regimen (Figures 1A and 1B) between August 2014 and May 2017 at our institution for inclusion in this analysis. Post-transplant immune suppression comprised of tacrolimus and either methotrexate or mycophenolate mofetil. The Institutional Review Board approved this analysis and a waiver of informed consent was obtained. Medical records of all patients were reviewed by participating investigators. Assessment of graft-versus-host disease (GVHD) was performed following standard grading practice. An analysis of 1-year GVHD-free, relapse-free survival (GRFS) was conducted and compared to an historical cohort of all SAA patients transplanted with a non-FCR regimen at our institution since January 1999 (n=27), with differences between the curves determined using log-rank tests.Results11 SAA patients underwent HCT from August 1, 2014 to May 5, 2017, the majority of which were male with a median age of 41 years (range: 19-64). Most patients received one line of treatment prior to HCT (CSA+ATG=6, CSA=1, steroids=1) and received an HCT within a median of 205 days after diagnosis (range: 70-2090). All patients received transplants from matched or haploidentical donors (matched related=4, matched unrelated=5, haploidentical=2) using a peripheral blood stem cell source, except 1 patient who received a bone marrow graft. At median follow-up of 302 (range: 49-911) days post-transplant, all patients were alive and in remission with 100% donor peripheral blood chimerism with bone marrow biopsies documenting normal trilineage hematopoiesis. Average time to neutrophil and platelet engraftment was 15.4 days and 16 days, respectively. The median number of inpatient hospital days required in the first 100 days post-transplant was 11 days (range: 3-29). By day 100 post-transplant, 54.5% of patients developed some degree of acute GVHD (grade I=1, grade II=3, grade III=2). However, by date of last follow-up, all evaluable patients (10/11) had not developed chronic GVHD. Only 2 patients experienced a viral reactivation (1=cytomegalovirus (CMV), 1=CMV+EBV) by date of last follow-up post-transplant. The case of EBV reactivation did not require treatment and no patients developed post-transplant lymphoproliferative disorder. The unadjusted Kaplan-Meier estimate of 1-year GRFS was 81.8% (95% CI: 59.1-104.7%) in the study group versus 61.5% (95% CI: 42.9-80.1%) in the historical group (P=0.256) (Figure 1C) with death accounting for the greatest proportion of GRFS events in the historical population and grade III acute GVHD accounting for the two GRFS events in the study cohort.ConclusionsThe positive results from this study demonstrating low toxicity, GVHD, and EBV reactivation rates with no graft failure or relapse potentially justify the use of these novel outpatient non-myeloablative conditioning regimens in SAA patients of any age receiving transplantation from any donor source. Further prospective investigation in a larger population is warranted. [Display omitted] DisclosuresGatwood:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Byrne:Pfizer: Membership on an entity's Board of Directors or advisory committees; Concert Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding. Jagasia:Therakos: Consultancy, Research Funding; Mallinckrodt: Consultancy; Janssen: Consultancy, Research Funding. Savani:Jazz Pharmaceuticals: Speakers Bureau.

Donor-Host Lineage-Specific Chimerism Monitoring and Analysis in Pediatric Patients Following Allogeneic Stem Cell Transplantation: Influence of Pretransplantation Variables and Correlation with Post-Transplantation Outcomes

The impact of donor-host chimerism in post-hematopoietic stem cell transplantation (HSCT) outcomes is poorly understood. We were interested in studying whether pre-HSCT variables influenced lineage-specific donor-host chimerism and how lineage-specific chimerism impacts post-HSCT outcomes. Our main objective was to study pre-HSCT variables as predictors of lineage-specific donor-host chimerism patterns and to better characterize the relationship between post-HSCT lineage-specific chimerism and adverse outcomes, including graft failure and disease relapse. We conducted a retrospective data analysis of all patients who underwent allogeneic HSCT at the Pediatric Transplantation and Cellular Therapy service at Memorial Sloan Kettering Cancer Center between January 2010 and June 2015 and had at least 2 measurements of split-lineage chimerism. The trend of lineage-specific donor-host chimerism post-HSCT and the impact of age, disease, graft type, and pretransplantation conditioning regimen on chimerism at 3 months and 12 months post-HSCT were studied. The Wilcoxon signed-rank test, Mann-Whitney-Wilcoxon test, and Cox proportional hazard models were used for statistical analyses. A total of 137 patients were included (median age, 11.3 years). Most patients had a hematologic malignancy (n=95), and fewer had a nonmalignant disorder (n=27) or primary immune deficiency (n=15). Myeloablative conditioning regimens (n=126) followed by T cell-depleted (TCD) peripheral blood stem cell or bone marrow grafts (n=101) were most commonly used. Mixed chimerism (MC) of total peripheral blood leukocytes (PBLs) did not predict loss of donor chimerism in all lineages and when stable was not associated with graft failure or rejection in this analyses. Split chimerism with complete donor chimerism (CC) of myeloid, B, and natural killer cells, but not T cells, occurred early post-HSCT, but full donor T cell chimerism was achieved at 12 months post-HSCT by most patients. MC within the T cell lineage was the major contributor to PBL MC, with lower median donor T cell chimerism at 3 months than at 12 months (91%) post-HSCT (51% versus 91%; P < .0001).Predictors of MC at 3 and 12 months were (1) age <3 years (P=.01 for PBLs and P=.003 for myeloidlineage); (2) nonmalignant disorder (P=.007 for PBLs); and (3) the use of reduced-intensity conditioning regimens. TCD grafts produced lower donor T cell chimerism at 3 months post-HSCT compared with unmodified grafts (P < .0001), where T cell lineage CC was achieved early post-HSCT. The donor T cell chimerism was similar at 12 months in the 2 types of grafts. Umbilical cord blood grafts had CC in all lineages at all time points post-HSCT. Loss of donor B cell chimerism was associated with increased risk of relapse in hematologic malignancies (hazard ratio, 1.33; P=.05). Age, underlying disease, conditioning regimen, and graft manipulation can impact post-HSCT donor-host chimerism and be predictors for early MC. MC in total PBLs and T cells was not related to graft failure or disease relapse. Whole-blood PBL chimerism analysis is not sufficient to assess the significance of post-HSCTdonor-host status; rather, lineage-specific chimerism, particularly for myeloid, T, and B cells, should be analyzed to guide interventions and inform outcomes.

Incidence, Management, and Prognosis of Graft Failure and Autologous Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation.

BackgroundThis study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR).MethodsWe analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000–September 2017) at our center.ResultsPrimary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34+ cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse.ConclusionPrimary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.

Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) was the first successful therapy for patients with haematological malignancies, predominantly owing to graft-versus-tumour (GvT) effects. Dramatic methodological changes, designed to expand eligibility for allo-HSCT to older patients and/or those with comorbidities, have led to the use of reduced-intensity conditioning regimens, in parallel with more aggressive immunosuppression to better control graft-versus-host disease (GvHD). Consequently, disease relapse has become the major cause of death following allo-HSCT. Hence, the prevention and treatment of relapse has come to the forefront and remains an unmet medical need. Despite >60 years of preclinical and clinical studies, the immunological requirements necessary to achieve GvT effects without promoting GvHD have not been fully established. Herein, we review learnings from preclinical modelling and clinical studies relating to the GvT effect, focusing on mechanisms of relapse and on immunomodulatory strategies that are being developed to overcome disease recurrence after both allo-HSCT and autologous HSCT. Emphasis is placed on discussing current knowledge and approaches predicated on the use of cell therapies, cytokines to augment immune responses and dual-purpose antibody therapies or other pharmacological agents that can control GvHD whilst simultaneously targeting cancer cells.

Fludarabine Melphalan Versus Fludarabine Treosulfan As Reduced Intensity Conditioning Regimens in Allogeneic Hematopoietic Stem Cell Transplant - a Retrospective Analysis

Introduction Allogeneic hematopoietic stem cell transplantation (AHSCT) has evolved as a curative therapy for various hematological malignancies. Regimen-related toxicity and transplant-related mortality (TRM) preclude the use of myeloablative conditioning (MAC) regimens in older and unfit patients. Reduced intensity conditioning (RIC) regimens have enabled AHSCT in such patients. There is a recent rise in use of RIC regimens even in younger patients in view of decreased toxicity and equal efficacy as reported in some studies. Fludarabine + Melphalan (FM) and Fludarabine + Treosulfan (FT) are 2 such regimens. There are no prospective randomised comparisons between these regimens. We retrospectively analysed these 2 regimens for toxicities and outcomes. Methods This is a retrospective single centre analysis of all consecutive patients with haematological cancers who received either FM or FT from April 2008 to December 2018. The entire cohort was divided into two groups - Matched Sibling Donor (MSD)/Matched Unrelated Donor (MUD) and Haploidentical (Haplo) transplants for analysis. We compared patient characteristics, toxicities and outcomes in both the groups based on conditioning regimen. The FT regimen consisted of fludarabine (30 mg/m2 on days − 6 to − 2) combined with treosulfan (12-14 gm/m2 on days − 6 to − 4) with or without 2 Gy TBI on day-1. The FM regimen consisted of fludarabine (30 mg/m2 on days − 7 to − 3) combined with melphalan (140 mg/m2 on day -1).Prophylaxis for GVHD consisted of calcineurin inhibitor (CNI) plus methotrexate (MTX)or mycophenolate mofetil (MMF) in MSD/MUD. Rabbit ATG (2.5-5 mg/kg) was used for MUD. Haplo transplant patients received post-transplant cyclophosphamide with CNI and MMF. Comorbidities were scored according to the HCT-CI. Disease Risk Index(DRI) and EBMT score were recorded for all patients. Neutrophil (NE) and platelet engraftment (PE) were defined as per standard criteria. Early toxicity after AHCT was graded according to CTCAE version 4. Total parenteral nutrition (TPN) was used in patients as per the physician's discretion. Acute GVHD and chronic GVHD were recorded according to standard criteria. All patients underwent chimerism studies at day 15, 30 and then monthly for 1 year. Mixed chimerism was defined as &gt; 5% to &lt; 95% donor chimerism. The toxicities in various arms were compared by Chi-square test or Fisher exact test, while OS was calculated by Kaplan Meier method and the survival probabilities were compared using log-rank test. Competing risk analysis was used to calculate cumulative incidence of relapse and TRM. Results The study included 138 patients, 98 males and 40 females. The diagnoses were AML- 53, ALL- 30, MDS/MPN- 49 and lymphoma -6. Patient characteristics are outlined in Table 1. MSD/MUD transplants were 105 (FM- 94; FT-11); 33 were Haplo (FM-17; FT-16) transplants. PBSC was the stem cell graft in 136 (99%) patients. In both MSD/MUD and Haplo groups, there were no significant differences in median age, gender, pre transplant CMV status, HCT-CI and EBMT score between the two conditioning regimens. In MSD/MUD group, significantly more patients had high/very high DRI in FT arm (45% vs 17%; P=0.056) Comparison of engraftment and toxicity variables of both FM and FT arms are outlined in Table 2. In MSD/MUD group, 44 (47%) patients in FM arm had grade 3/4 oral mucositis compared to 1 (9%) in FT arm (P=0.02). Corresponding numbers were 7 (41%) and 1 (6%) in Haplo group (P=0.039). Grade 3/4 diarrhoea was higher in the FM vs FT arm of Haplo group (41% vs 6%; P=0.039) but not in the MSD/MUD cohort. More patients received TPN in the FM arms of both MSD/MUD and Haplo groups (Table 2). Incidence of grade III-IV acute GVHD was higher in FT vs FM in MSD/MUD group (27% vs 17%; P=0.04). The median follow up of entire cohort was 4.8 years. The OS (figure 1) at 5 years was 62% in FM arm of MSD/MUD group vs 53% in FT arm (P=NS). Similarly OS (figure 2) at 5 years was 41% and 28 %( P=NS) in FM and FT arms respectively of Haplo group. The cumulative incidence of TRM and relapse at 2 years were not different in FM and FT arms of both MSD/MUD and Haplo groups (Table 2). Conclusion Grade 3 and 4 oral mucositis and diarrhoea were significantly less with FT than FM in both MSD/MUD and Haplo groups. FT provided comparable outcomes to FM in the MSD / MUD group in spite of having higher proportions of patients with high / very high DRI. Prospective randomised studies are required to compare various RIC regimens. Disclosures No relevant conflicts of interest to declare.

Trends in the use of hematopoietic stem cell transplantation for adults with acute lymphoblastic leukemia in Europe: a report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Hematopoietic stem cell transplantation (HSCT) is considered an effective way to prevent relapse in adults with acute lymphoblastic leukemia (ALL). This study aimed to assess general trends in the use of various types of HSCTs performed between 2001 and 2015 in Europe, based on data reported to the European Society for Blood and Marrow Transplantation registry. We also evaluated HSCT rates with respect to ALL incidence in selected countries. Altogether, 15,346 first allogeneic (n = 13,460) or autologous (n = 1886) HSCTs were performed in the study period. Comparing 2013–2015 and 2001–2003, the number of allogeneic HSCTs performed in first complete remission increased by 136%, most prominently for transplantations from unrelated (272%) and mismatched related donors (339%). The number of HSCTs from matched sibling donors increased by 42%, while the total number of autologous HSCTs decreased by 70%. Increased use of allogeneic HSCT was stronger for Philadelphia chromosome (Ph)-positive (166%) than for Ph-negative ALL (38%) and for patients aged > 55 years (599%) than for younger adults (59%). The proportion of allogeneic HSCT with reduced-intensity conditioning (RIC) increased from 6 to 27%. The age-standardized rates of allogeneic HSCT per ALL incidence varied strongly among countries. Our analysis showed a continued trend toward increased allogeneic HSCT use for adults with ALL, which may be attributed to increasing availability of unrelated donors, wider use of RIC regimens, and improving efficacy of pretransplant therapy, including tyrosine kinase inhibitors for Ph-positive ALL. Allogeneic HSCT remains a major tool in the fight against ALL in adults.

Limitations to Receiving Allogeneic Hematopoietic Cell Transplantation for Treatment of Acute Myeloid Leukemia: A Large Multi-Center Prospective Longitudinal Observational Study

Introduction Older pts with AML often have significant comorbidities and other geriatric health problems, and the effect of these on the probability of receiving HCT is unknown. We designed a prospective, longitudinal, observational study of adult pts with AML dating from first presentation at one of 13 centers. We examined the effects of different variables on the probability to 1) survive long enough to receive HCT and 2) to receive HCT if such survival occurred. Methods We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), response, age, comorbidities per the HCT-comorbidity index (CI), function, frailty, geriatric assessment, cognition, Karnofsky performance status (KPS), QOL, social support, and depression were collected at enrollment and at 1, 3, 6, 9, 12, 18, and 24 months thereafter. We used competing risk Cox regression analyses, treating HCT as the event of interest and death without HCT as a competing risk, with staggered entry (left truncation) at time of consent. Associations between variables were assessed both at enrollment and over time. Results The overall rate of HCT at 9 months after enrollment was 43% (Figure 1) and 92% who received HCT did so by 9 months. In multivariate analyses, death without HCT (Table 2) was associated with augmented HCT-CI scores ≥5, age ≥50 years with those aged ≥70 years having the highest association, ELN intermediate or unfavorable risks, receiving low-intensity induction regimens, relapsed/refractory disease at enrollment, dependent status per ADL scores Among survivors (Table 3), low likelihood to receive HCT was associated with age ≥70 years, low ELN risk, low-intensity induction, poor KPS, and relapse after initial complete remission (CR); while pts with high-risk MDS, relapsed/refractory disease at enrollment, and CR after induction were more likely to receive HCT. Among pts aged ≥60 years, and after considering previous factors, impaired cognition and hearing had a lower likelihood to receive HCT. Conclusions Increasing age, comorbidity burden, ELN risk, low-intensity initial AML induction regimen, depression, and functional dependence increase risks of early mortality without HCT. In those who survived long enough to potentially receive HCT, age up to 69 years and/or multiple comorbidities were not found to be barriers to HCT, likely reflecting the widespread use of reduced-intensity conditioning regimens. The adverse impact of impairments in psychological health and function on survival and of impairments of cognition, geriatric health, and performance status on receipt of HCT emphasize the need for interventions that target these health limitations in conjunction with AML treatment to improve outcomes. Finally, the benefit of intensive vs. less-intensive induction therapies should be addressed with a randomized trial.

Reduced-Intensity Conditioning Versus Myeloablative Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients with Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis of Randomized Trials

Background:Allogenic hematopoietic cell transplantation (alloHCT) is a curative option for patients with high-risk myelodysplastic syndrome (MDS). The benefit of higher conditioning intensity in MDS is controversial. While myeloablative conditioning (MAC) regimens can mitigate the risk of relapse, they are associated with higher non-relapse mortality (NRM). In contrast, the reduced intensity conditioning (RIC) regimens are associated with higher risk of relapse. And owing to the lower NRM, they are feasible in patients with advanced age or comorbidities.Methods:We report here a systematic review and meta-analysis of randomized controlled trials (RCTs) that directly compared the safety and efficacy of MAC vs RIC regimens in MDS. The efficacy was evaluated in terms of overall survival (OS), relapse-free survival (RFS) and relapse incidence (RI). The safety was evaluated in terms of non-related mortality (NRM) and incidence of acute (a) and chronic (c) graft-versus-host disease (GVHD). A systematic search of databases using PubMed, Embase, Web of science, Cochrane database and Clinicaltrials.gov was performed on May 6th, 2018 with no restrictions of language or time period. RCTs comparing MAC with RIC regimens that include MDS patients were considered eligible for inclusion. After duplicates removal, a total of 683 articles were scrutinized for relevance by screening the abstracts and/or full length articles. Based on the eligibility criteria, only two randomized studies (BMT CTN 0901 Trial Scott, B. et al. 2017 & EBMT RICMAC Trial Kroger, N. et al. 2017) qualified for inclusion and quantitative synthesis. The quality assessment was done using the Cochrane tool regarding the bias in study selection, performance, detection, attrition and reporting of the clinical trials.Results:Out of total 392 MDS and acute myeloid leukemia (AML) patients enrolled in these two trial, 169 patients had MDS (N=115 in Kroger et al and N=54 cases in Scott et al). Eighty one patients received MAC and 88 patients received RIC followed by either a related or unrelated alloHCT. The median age range at the time of transplant was 50-54 years and these patients were followed for a period of 18-24 months. There were no statistically significant differences in the baseline patient characteristics between two regimen groups in the both trials. The use of RIC regimen was associated with a statistically non-significant trend towards improved OS (OR 1.52: 95% CI: 0.93-2.5, p-value= 0.097), along with a significantly reduced risk of NRM (OR 0.39: 95% CI: 0.16-0.94, p-value= 0.04). The RIC alloHCT was not associated with a higher risk of disease relapse (OR: 4.24, 95% CI: 0.34-52.22, p-value= 0.26) or inferior RFS (OR: 0.64, 95% CI: 0.196-2.06, p-value= 0.45). There was no difference between the two conditioning intensities in terms of risk of developing aGVHD (OR: 0.51, 95% CI: 0.11-2.27, p-value= 0.37) or cGVHD (OR: 0.50, 95% CI: 0.18-1.40, p-value= 0.19). The meta-analysis results are shown in figure-1. The Infectious complications were comparable for both groups in Scott, et al. But Kroger et al reported significantly lower overall infections rate at day 100 (4.3 vs. 6.9, p=0.002) and at total follow up (1.4 vs. 2.0, p= 0.002) for RIC.Conclusion:In adult patients with MDS undergoing alloHCT, RIC regimens were associated with a significantly lower risk of NRM, without increased risk of relapse, mortality or GVHD. It is unknown if any specific poor risk groups regarding clinical indicators (e.g. IPSS score) or genomic predictors (e.g. p53 mutations or RAS pathway mutations) may benefit from higher conditioning intensity and warrants further investigation. DisclosuresHamadani:Sanofi Genzyme: Research Funding, Speakers Bureau; ADC Therapeutics: Research Funding; Ostuka: Research Funding; Janssen: Consultancy; Merck: Research Funding; MedImmune: Consultancy, Research Funding; Cellerant: Consultancy; Celgene Corporation: Consultancy; Takeda: Research Funding.

Limitations to Receiving Allogeneic Hematopoietic Cell Transplantation for Treatment of Acute Myeloid Leukemia: A Large Multi-Center Prospective Longitudinal Observational Study

Introduction: Acute myeloid leukemia (AML) is most frequently diagnosed in older patients (pts), whose median survival is less than 1 year. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. However, older pts often have significant comorbidities and other geriatric health problems, and the effect of these on the probability of receiving HCT is unknown. To this end, we designed a prospective, multi-center, longitudinal, observational study dating from first presentation of adult pts with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We examined the effects of different variables (see methods) on the probability to 1) survive long enough to receive HCT and 2) to receive HCT if such survival occurred. Methods: We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), and response; age; comorbidities per the HCT-comorbidity index (CI); function including instrumental activities of daily living (IADL) and activities of daily living (ADL); frailty including walk test; geriatric assessment (GA) including cognition; Karnofsky performance status (KPS); QOL including the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), Euro-QOL 5-Dimension scale (EQ-5D), ENRICHD Social Support Instrument, Social Activity Log, and Patient Health Questionnaire 9-item Depression Scale (PHQ-9) were collected at enrollment and at 1, 3, 6, 9, 12, 18, and 24 months thereafter. High-risk myelodysplastic syndromes (MDS) receiving AML-like therapy were included. We used competing risk Cox regression analyses, treating HCT as the event of interest and death without HCT as a competing risk, with staggered entry (left truncation) at time of consent. Associations between variables were assessed both at enrollment and over time. Results: The overall rate of HCT at 9 months after enrollment was 43% (Figure 1) and 92% of pts who received HCT did so by the 9 month mark. In multivariate analyses, death without HCT (Table 2) was associated with augmented HCT-CI scores ≥5 (HR:2.11, p Among survivors (Table 3), low likelihood to receive HCT was associated with age ≥70 years (HR:0.40, p=0.0001), low ELN risk (HR:0.28, p Conclusions: In a prospective, observational, multi-center study, increasing age, comorbidity burden, ELN risk, low-intensity initial AML induction regimen, depression, and functional dependence increase risks of early mortality without HCT. In those who survived long enough to potentially receive HCT, age up to 69 years and/or multiple comorbidities were not found to be barriers to HCT, likely reflecting the widespread use of reduced-intensity conditioning regimens. However, the independent sharp decline in receipt of HCT in pts aged 70-80 years suggests continued bias, although pts in this age group have been shown to derive similar benefit from HCT as younger pts. Use of objective comorbidity and GA tools rather than age per se to decide on HCT is encouraged. The adverse impact of impairments in psychological health and function on survival and of impairments of cognition, geriatric health, and performance status on receipt of HCT emphasize the need for interventions that target these health limitations in conjunction with AML treatment to improve outcomes. Finally, the benefit of intensive vs. less-intensive induction therapies should be addressed with a randomized trial. Disclosures Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Shami:Lone Star Biotherapies: Equity Ownership; Baston Biologics Company: Membership on an entity9s Board of Directors or advisory committees; JSK Therapeutics: Employment, Equity Ownership, Membership on an entity9s Board of Directors or advisory committees; Pfizer: Consultancy. Rizzieri:Arog: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Novartis: Consultancy; Pfizer: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Teva: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Wang:Novartis: Speakers Bureau; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy; Jazz: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Consultancy; Jazz: Speakers Bureau; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Faderl:Jazz Pharmaceuticals: Employment, Equity Ownership. Koprivnikar:Amgen: Speakers Bureau; Otsuka: Consultancy; Alexion: Consultancy, Speakers Bureau. Sekeres:Celgene: Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees; Opsona: Membership on an entity9s Board of Directors or advisory committees; Opsona: Membership on an entity9s Board of Directors or advisory committees. Becker:GlycoMimetics: Research Funding.

Comparison of Myeloablative Conditioning Regimes Based on Either Busulfan or Total Body Irradiation in Combination with Fludarabine for Patients with Acute Myeloid Leukemia. a Study on Behalf of the Polish Adult Leukemia Group

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a standard of care for patients with high risk acute myeloid leukemia (AML). However, the procedure using conventional myeloablative conditioning regimens based on either busulphan (Bu) or total body irradiation (TBI) in combination with cyclophosphamide is associated with significant risk of non-relapse mortality (NRM). The use of reduced-intensity conditioning regimens results in improved tolerance but increased incidence of disease recurrence. In order to reduce toxicity while maintaining the anti-leukemic efficacy alternative conditioning regimens have been proposed including the use of Bu or TBI in combination with fludarabine (Flu). The goal of this retrospective, multicenter study was thus to compare Bu4Flu and TBI12Gy/Flu.Patients and methods: Adult patients with AML treated with alloHSCT from either HLA-matched sibling (MSD) or unrelated donor (URD) between year 2012 and 2017 were included in the analysis. The following conditioning regimens have been selected for the comparison: intravenous Bu at the total dose 12.8 mg/kg (4 days) + Flu (Bu4Flu, N=60) or TBI at the total dose of 12 Gy given in three fractions + Flu (TBI12Flu, N=40).Results: 100 patients (Bu4Flu, n=60; TBI4Flu, n=40) were included in the analysis. Median age was 42 (19-62) years in Bu4Flu group and 36 (19-64) for TBI12Flu group (p=0.01). Proportion of patients given transplant from URD was 72% and 70%, respectively (p=NS). The rates of patients treated with HSCT CR1, CR>1 and active disease were 75%, 25%, 0% in the Bu4Flu group while 82.5%, 10% and 7% in the TBI12Flu group (p=NS).All patients engrafted except for one patient in the TBI12Flu group who died of infection before engraftment. Time to neutrophil recovery was significantly faster after TBI12Flu (median 15 days, range 11-24) compared to Bu4Flu (18, 12-36 days) (p=0.000007). With the median follow up of 18 months, the cumulative incidence of relapse at 2 years was 11% (+/-6) and 30% (+/-7), respectively (p=0.14) while NRM was 19% (+/-8) and 10 (+/-5%), respectively (p=0.34). The probability of OS was 76% (+/-8) after TBI12Flu and 71% (+/-7%) after Bu4Flu (p=0.69). The LFS rates were 70% (+/-8%) and 60% (+/-7%), respectively (p=0.53). No signficant differences regarding survival could be detected in analysis restricted to patients transplanted in CR.Conclusion: Both Bu4Flu or TBI12Flu as conditioning regimens pre-alloHSCT for patients with AML are highly effective, which together with acceptable tolerance leads to survival rates of more than 70% at two years. TBI12Flu is associated with faster engraftment and a tendency to reduced risk of relapse. Prospective studies comparing both regiemens are needed. DisclosuresNo relevant conflicts of interest to declare.

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Chronic and Advanced Phase Myelofibrosis

Myelofibrosis (MF) is a chronic progressive hematologic malignancy with a median overall survival (OS) of approximately 6 years. Allogeneic hematopoietic stem cell transplantation (HSCT) is the sole treatment approach that offers curative potential. The use of reduced-intensity conditioning regimens has expanded the application of HSCT to patients with MF up to age 70 years. Recent retrospective and prospective reports have suggested worse HSCT outcomes for patients with MF receiving an unrelated donor graft compared with those receiving a related donor graft. To identify patient- and HSCT-specific variables influencing outcomes, we conducted a retrospective analysis of 42 patients with chronic and advanced-phase MF who underwent HSCT at our institution. For this cohort, at a median follow-up of 43 months, progression-free survival (PFS) was 15 months and OS was 25 months. In multivariable analysis, the sole clinical variable that negatively influenced outcome was the use of an unrelated donor, with a median PFS and OS both of 11 months versus not yet reached in patients receiving a related donor graft. At 2 years, OS was 38% (95% confidence interval [CI], 20%-56%) and nonrelapse mortality (NRM) was 53% (95% CI, 36%-78%) in the unrelated donor graft group, compared with 75% (95% CI, 46%-90%) and 21% (95% CI, 9%-47%) in the related donor graft group. There was no difference in the rates of grade III-IV acute graft-versus-host disease between the unrelated and related donor groups (38% versus 38%). Despite a more aggressive disease state, 2-year PFS and OS were both 42% (95% CI, 15%-67%) in patients with myeloproliferative neoplasm-blast phase undergoing HSCT. Graft failure rate was higher in patients receiving a mismatched donor graft compared with those receiving a matched donor graft (60% versus 13%; P = .0398). Retransplantation of patients with graft failure resulted in long-term survival. Baseline splenomegaly did not affect transplantation outcomes. Given the particularly poor outcomes seen in the unrelated donor cohort here and elsewhere, a formal exploration of alternative hematopoietic stem cell sources is warranted.

Haploidentical Bone Marrow Transplantation in 2015 and Beyond.

On the face of the lack of HLA-identical sibling stem cell donors for all individuals needing an allograft, the use of alternative donors is gaining popularity. Matched unrelated donors and cord bloods have become very expensive and unaffordable for most people living in developing countries. Grafting allogeneic haploidentical stem cells has become an option with a great future, mainly if the procedure is conducted in a way to cut down expenses, such as the use of reduced-intensity conditioning regimens, outpatient conduction of the procedures, and use of post-transplant cyclophosphamide. The long-term results of allografting haploidentical stem cells seem to be similar to those of grafting cord blood stem cells. The improvement of the procedures to conduct haploidentical stem cell transplantation will most likely result in more individuals gaining access to this type of treatments, critical in the current practice of hematology.

Outcome of allogeneic hematopoietic stem-cell transplantation for adult patients with AML and 11q23/MLL rearrangement (MLL-r AML).

Acute myeloid leukemia (AML) with 11q23/MLL rearrangement (MLL-r AML) is allocated to the intermediate- or high-risk cytogenetic prognostic category depending on the MLL fusion partner. A more favorable outcome has been reported in patients receiving an allogeneic hematopoietic stem-cell transplantation (alloHSCT), but this has not been confirmed in large series. We analyzed the outcome of alloHSCT among adult patients reported to the Acute Leukemia Working Party between 2000 and 2010. We identified 159 patients with 11q23/MLL rearranged AML allografted in first complete remission (CR1, n=138) or CR2, mostly corresponding to t(9;11), t(11;19), t(6;11) and t(10;11) translocations. Two-year overall survival (OS), leukemia-free survival (LFS), relapse incidence and non-relapse mortality were 56±4%, 51±4%, 31±3% and 17±4%, respectively. The outcome differed according to 11q23/MLL rearrangement, being more favorable in patients with t(9;11) and t(11;19) compared with t(10;11) and t(6;11) (2-year OS: 64±6% and 73±10% vs 40±13% and 24±11%, respectively; P<0.0001). Multivariate analysis for OS identified t(6;11), t(10;11), age>40 years and CR2 as unfavorable features, whereas t(6;11), t(10;11), CR2 and the use of reduced-intensity conditioning regimen affected poorly the LFS. This study confirms the potential role of alloHSCT for adult patients with 11q23/MLL rearranged AML in CR1.

Indications actuelles de l’allogreffe de cellules souches hématopoïétiques dans le traitement de la leucémie aiguë myéloïde de l’adulte

Allogeneic stem cell transplantation (SCT) is an increasingly important therapeutic option for the treatment of adult patients with acute myeloid leukemia. Here we review the current indications of SCT in this disease. While patients with favorable cytogenetics should receive consolidation chemotherapy, patients with unfavorable karyotype are prime candidates for SCT or new approaches to SCT (which should be done in first complete remission). Patients with intermediate prognoses should also receive SCT in first complete remission. In the absence of a suitable matched related donor, most patients will be able to find an alternative donor to proceed to a potentially curative allogeneic transplantation. The use of reduced-intensity conditioning regimens before SCT has allowed patients in the sixth or seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immune-modulation, and supportive care, there has been a dramatic improvement in terms of tolerance. Although it is presumed to be a curative strategy, major complications of SCT remain graft-versus-host disease, delayed immune recovery, multiple comorbidities, and relapse after transplant.

Hematopoietic stem cell transplantation for follicular lymphoma: optimal timing and indication.

The definitive management of advanced follicular lymphoma (FL) remains controversial due to various treatment options, including watchful waiting, single-agent or combination chemotherapy, monoclonal antibody, and radioimmunotherapy. These options can provide prolonged progression-free survival. However, they cannot cure advanced FL. Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the sole curative therapy for FL. Allo-SCT has had a major impact with the use of reduced-intensity conditioning regimens because of its lower associated nonrelapse mortality compared with myeloablative regimens. Autologous SCT (auto-SCT) shows high response rates and extends progression-free survival in patients with chemosensitive relapse. In the rituximab era, however, associated comorbidities, risk of secondary cancers, and presence of refractory disease have become problematic in the auto-SCT population. On the basis of results from large-scale randomized trials, upfront auto-SCT is not recommended. Novel conditioning regimens including radioimmunotherapy followed by either auto-SCT or allo-SCT are likely to show efficacy even in chemorefractory disease. Consequently, the optimal timing for SCT remains a matter of opinion, except for patients in first remission. However, the outcomes of allo-SCT and auto-SCT keep on improving. Physicians should note that there is no therapy with a track record equivalent to that of SCT for relapsed or refractory FL.

Unrelated Umbilical Cord Blood Transplantation: Characteristics and Outcomes In Older Patients With Hematological Malignancies In Europe and United States: A Eurocord/European Group For Blood and Marrow Transplantation (EBMT) and Center For International Blood and Marrow Transplant Research (CIBMTR) Study

IntroductionTransplantation with umbilical cord blood rather than adult donor cells is a valid alternative for adults with malignant and non-malignant hematological diseases. The use of unrelated umbilical cord blood transplantation (UCBT) in adults has increased recently for 2 reasons: use of 2 cord blood units to obtain an adequate number of cells; and, use of reduced-intensity conditioning regimens (RIC) for older persons who are unable to tolerate myeloablative conditioning regimens. Recent data from Eurocord and CIBMTR indicate that 35% of adults UCBT recipients are older than 50 years. This study describes the increasing use of UCBT and the patient characteristics and transplant strategies used in older (>50 years) patients receiving UCBT in Europe and United States, as well as UCBT outcomes in this population. MethodsRetrospective registry based cross-sectional study on patients transplanted in Europe and North America; Patients: 1529 patients 50 years or older who received UCBT for hematologic malignancies or non-malignant hematologic disorders from 2005 through 2011, and whose transplants were reported to EUROCORD/EBMT or CIBMTR. 848 patients were transplanted in North America; 681 were transplanted in Europe. Acute myeloid leukemia (AML) (50%) was the most frequent indication in both registries, followed by myelodysplastic syndrome (MDS) and non-Hodgkin Lymphoma (NHL). Myeloma (MM) was the indication for UCBT for 15% of patients in Europe, but accounted for only a single case in the US (Refer to table 1 for complete UCBT distribution according to diagnosis). Most AML patients (80%) in both registries were transplanted in CR1 or CR2. RIC regimens were used more frequently for patients in Europe: 76% of patients reported to Eurocord versus 49% reported to CIBMTR for patients in the age range 50-59y and 93% in Eurocord and 69% in CIBMTR for patients 60y or older. Graft-versus-host disease prophylaxis in Europe was predominantly with cyclosporine and prednisone; tacrolimus and mycophenolate was more often used in the US. Double UCBT accounted for 61% of cases reported to Eurocord and for 71% of cases reported to CIBMTR.Table 1Number of UCBT by DiagnosisEurocord, n=681CIBMTR, n=848ALL5266AML283435MDS/MPD138121CML2121CLL4468NHL83118HD310MM491Solid Tumor4Bone Marrow Failure Syndrome44 ResultsProbability of 2-y overall survival (OS) was similar in both cohorts. In Eurocord, 2-y OS rates were 33% for AML in CR1, 48% in CR2, 10% with advanced disease for patients aged 50-59y; corresponding rates in older patients were 58%, 29% and 15%, respectively. In CIBMTR, 2-y OS rates were 41% for AML in CR1, 30% in CR2 and 15% with advanced disease for patients aged 50-59y; corresponding rates for older patients were 22%, 29%, and 16%, respectively. For other malignancies, in Eurocord, for patients aged 50-59y, 2-y OS rates were 57% in MM, 52% in ALL (acute lymphocytic leukemia), 49% in NHL, 47% in CLL (chronic lymphocytic leukemia) and 25% in MDS. In CIBMTR, corresponding OS rates were 54% in ALL, 48% in MDS, 41% in NHL and 40% in CLL ConclusionThe number of UCBT for the elderly has been increasing over the years, and survival rates are comparable for this population in Europe and North America, with similar trends in both registries. The encouraging results of this survey show that UCBT is a good alternative source of stem cells for elderly patients with hematologic diseases. Comparative studies between umbilical cord blood and other stem cell sources are needed to define the best graft indication for patients aged 50 years and older lacking an HLA identical adult donor. Disclosures:No relevant conflicts of interest to declare.

Intensification Of Treosulfan and Fludarabine-Based Conditioning With 4 Gy TBI For Allogeneic Stem Cell Transplantation In Patients With Hematological Malignancies

BackgroundHematopoietic stem cell transplantation (HSCT) is so far the only potentially curative option for patients with aggressive hematological malignancies. Since many patients cannot find a suitable HLA-identical (related or unrelated) donor, it is essential to analyze the safety of alternative graft sources, such as haploidentical donors. The use of reduced-intensity conditioning regimens in patients with an advanced disease did not improve the outcome because of a higher incidence of relapse. Here we present an interim analysis of this phase II prospective clinical trial that investigates a new conditioning regimen for allogeneic HSCT based on a well established one (Fludarabine and Treosulfan) intensified adding 4 Gy TBI with the aim of maintaining an acceptable toxicity profile while reducing the incidence of relapse in high-risk patients (TrRaMM4Gy study, Eudract 2011-001534-42). Patients and MethodsNinety-six patients underwent allogeneic HSCT for AML (n=46), ALL (n=13), acute biphenotypic leukaemia (n=2), HD (n=8), NHL (n=7), MDS (n=6), Myelofibrosis (n=5), MM (n=4), CML (n=2), CMML (n=2) or CLL (n=1). The median age was 45 years (range 17-67). At the time of the transplantation most patients (n=76) were in advanced disease phase, while the remaining 20 patients were in early phase. Twenty-eight patients were enrolled for relapse after a previous allogeneic HSCT. Median time from diagnosis to transplantation was 443 days (range 56-5249). Median comorbodity index score (according to Sorror criteria) was 2 (range: 0-8). Sixty-two patients received the graft from haploidentical donors, 17 from MUD, 14 from HLA-identical sibling and 3 patients from a single cord blood unit. Median number of CD34+ and CD3+ cells/kg were 6.46 millions and 241 millions respectively. The conditioning regimen included Treosulfan (14 g/m2 for 3 days), Fludarabine (30 mg/m2 for 5 days) and 4 Gy TBI split in 2 fractions. Patients receiving HSCT from haploidentical donor (arm A) were also treated with ATG-Fresenius (10 mg/kg for 3 days) and Rituximab (200 mg/m2 in single dose), patients receiving HSCT from HLA-identical sibling, MUD or single cord blood unit and in early disease status (arm B) were also treated with ATG-Fresenius (5 mg/kg for 3 days) and Rituximab (200 mg/m2 in single dose), while patients receiving HSCT from HLA-identical sibling, MUD or single cord blood unit and in advanced disease status (arm C) did not receive any ATG or Rituximab. GvHD prophylaxis consisted of Sirolimus (target concentration 8-15 ng/ml, till day +60) and Mycophenolate Mofetil (10 mg/kg tid till day +30). ResultsNeutrophils engraftment was reported at a median time of 17 days (range: 9-46) in all 91 evaluable patients; five patients died of transplant-related causes (n=4) or disease progression (n=1) before day +15. Platelets engraftment occurred after a median time of 17 days (range: 4-153) in 75 patients (82%). At the first marrow evaluation on day +30 all the evaluable patients showed full donor chimerism, 77 patients (90%) were in complete remission and 9 were in stable disease or progression. After a median follow-up of 425 days, cumulative incidence of grade 2-4 and 3-4 aGvHD were 40% and 26% respectively. Cumulative incidence of moderate or severe cGvHD (according to NIH criteria) was 57%. Cumulative incidence of NRM at day +100 and +365 were 23% and 36% respectively; cumulative incidence of relapse at day +365 was 33%. Overall survival and progression-free survival 1 year after HSCT were 51% and 43% respectively. EBV reactivation occurred in 7 patients, but no PTLD was observed. ConclusionsThe new conditioning regimen we investigated proved to be feasible in this high-risk population. We did not observe any major difference in terms of NRM and aGvHD compared to the data from our previous trial (TrRaMM, Eudract 2007-5477-54) with similar inclusion criteria and patient characteristics, but a reduced-intensity conditioning regimen based on Treosulfan and Fludarabine. Interestingly, we observed a trend of lower relapse incidence, resulting in a better OS and PFS. The low toxicity profile of Treosulfan and Fludarabine should be considered as a myeloablative platform for further intensification; more studies are warranted in order to find the association for a conditioning regimen endowed with a low toxicity profile but still a strong anti-tumor activity. Disclosures:Bonini:MolMed SpA: Consultancy.

Hematopoietic Cell Transplantation–Specific Comorbidity Index Predicts Inpatient Mortality and Survival in Patients Who Received Allogeneic Transplantation Admitted to the Intensive Care Unit

To investigate the prognostic value of the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) in patients who received transplantation admitted to the intensive care unit (ICU). We investigated the association of HCT-CI with inpatient mortality and overall survival (OS) among 377 patients who were admitted to the ICU within 100 days of allogeneic stem-cell transplantation (ASCT) at our institution. HCT-CI scores were collapsed into four groups and were evaluated in univariate and multivariate analyses using logistic regression and Cox proportional hazards models. The most common pretransplantation comorbidities were pulmonary and cardiac diseases, and respiratory failure was the primary reason for ICU admission. We observed a strong trend for higher inpatient mortality and shorter OS among patients with HCT-CI values ≥ 2 compared with patients with values of 0 to 1 in all patient subsets studied. Multivariate analysis showed that patients with HCT-CI values ≥ 2 had significantly higher inpatient mortality than patients with values of 0 to 1 and that HCT-CI values ≥ 4 were significantly associated with shorter OS compared with values of 0 to 1 (hazard ratio, 1.74; 95% CI, 1.23 to 2.47). The factors associated with lower inpatient mortality were ICU admission during the ASCT conditioning phase or the use of reduced-intensity conditioning regimens. The overall inpatient mortality rate was 64%, and the 1-year OS rate was 15%. Among patients with HCT-CI scores of 0 to 1, 2, 3, and ≥ 4, the 1-year OS rates were 22%, 17%, 18%, and 9%, respectively. HCT-CI is a valuable predictor of mortality and survival in critically ill patients after ASCT.

Changing role of stem cell transplantation in follicular lymphoma

Abstract Patients with advanced follicular lymphoma (FL) have numerous treatment options, including observation, radiotherapy, single-agent or combination chemotherapy, mAbs, and radioimmunoconjugates. These therapies can extend progression-free survival but none can provide a cure. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curable therapy for FL, with the field shifting more toward the use of reduced-intensity conditioning regimens because of the lower associated nonrelapse mortality compared with myeloablative regimens. However, GVHD and infection are still problematic in the allo-HSCT population. Autologous HSCT (auto-HSCT) confers high response rates and prolongs progression-free survival in relapsed patients who are chemosensitive, and an increasing amount of data suggest that auto-HSCT may be curative if offered to relapsed patients who are not heavily pretreated. Auto-HSCT has no role as consolidation therapy for patients in first remission based on the results from 3 large randomized trials. Novel conditioning regimens with radioimmunoconjugates have been used in both auto-HSCT and allo-HSCT regimens and results have shown efficacy even in chemorefractory patients. Therefore, with the exception of patients in first remission, the optimal timing for HSCT remains controversial. However, the outcomes seen after auto-HSCT and allo-HSCT continue to improve, and HSCT represents a treatment modality that should be considered in all FL patients, especially while their disease remains chemoresponsive.

Changing role of stem cell transplantation in follicular lymphoma.

Patients with advanced follicular lymphoma (FL) have numerous treatment options, including observation, radiotherapy, single-agent or combination chemotherapy, mAbs, and radioimmunoconjugates. These therapies can extend progression-free survival but none can provide a cure. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curable therapy for FL, with the field shifting more toward the use of reduced-intensity conditioning regimens because of the lower associated nonrelapse mortality compared with myeloablative regimens. However, GVHD and infection are still problematic in the allo-HSCT population. Autologous HSCT (auto-HSCT) confers high response rates and prolongs progression-free survival in relapsed patients who are chemosensitive, and an increasing amount of data suggest that auto-HSCT may be curative if offered to relapsed patients who are not heavily pretreated. Auto-HSCT has no role as consolidation therapy for patients in first remission based on the results from 3 large randomized trials. Novel conditioning regimens with radioimmunoconjugates have been used in both auto-HSCT and allo-HSCT regimens and results have shown efficacy even in chemorefractory patients. Therefore, with the exception of patients in first remission, the optimal timing for HSCT remains controversial. However, the outcomes seen after auto-HSCT and allo-HSCT continue to improve, and HSCT represents a treatment modality that should be considered in all FL patients, especially while their disease remains chemoresponsive.