100-day Treatment-related Mortality Research Articles

Salvage hematopoietic stem cell transplantation for patients with higher leukemia burden in relapsed or refractory acute myeloid leukemia: a ten-year study.

Patients with relapsed and refractory acute myeloid leukemia (R-R AML), especially those in non-remission (NR) have a poor prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to optimize the entire allo-HSCT process for R-R AML patients and identify potential factors affecting clinical outcomes after HSCT, we retrospectively analyzed 44 adult patients with R-R AML who underwent salvage allo-HSCT while in NR or with concomitant extramedullary leukemia at the Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2013 to 2022. The 1-year and 2-year overall survival (OS) of the 44 patients were 55.3% (95% confidence interval [CI], 41.1%-74.3%) and 44.4% (95%CI, 30.2%-65.4%), respectively. The 1-year and 2-year cumulative incidence of relapse (CIR) were 39.4% (95%CI, 38.0%-40.7%) and 53.0% (95%CI, 51.0%-55.1%), respectively, and the 1-year and 2-year leukemia-free survival (LFS) were 37.8% (95%CI, 24.8%-57.7%) and 20.3% (95%CI, 9.1%-45.3%), respectively. The 100-day, 1-year and 2-year treatment-related mortality (TRM) was 13.8% (95%CI, 13.3%-14.4%), 22.8% (95%CI, 21.9%-23.7%) and 26.7% (95%CI, 25.5%-27.8%), respectively. Multivariate analysis revealed that patients who developed chronic graft-versus-host disease (cGVHD) after transplantation had lower relapse rate. Our analysis also indicated that patients with blast counts in bone marrow (BM) <20% and those with ≥20% had comparable clinical outcomes after allo-HSCT. In conclusion, our study demonstrated that R-R AML patients in NR or with concomitant extramedullary leukemia can benefit from allo-HSCT, regardless of leukemia burden at the time of transplantation. Patients who experience cGVHD after allo-HSCT may have lower relapse rate due to enhanced graft-versus-leukemia (GVL) effects, but cGVHD should be controlled at mild to moderate level to avoid life-threatening complications.

Predictors of hematologic response and survival with stem cell transplantation in AL amyloidosis: A 25-year longitudinal study.

High-dose melphalan and stem cell transplantation (HDM/SCT) is an effective treatment for selected patients with AL amyloidosis. We report the long-term outcomes of 648 patients with AL amyloidosis treated with HDM/SCT over 25 years. Hematologic CR was achieved by 39% of patients. The median duration of hematologic CR was 12.3 years, and 45% of patients with a hematologic CR had no evidence of a recurrent plasma cell dyscrasia at 15 years after HDM/SCT. With a median follow-up interval of 8 years, the median event-free survival (EFS) and overall survival (OS) were 3.3 and 7.6 years, respectively. Patients with a hematologic CR had a median OS of 15 years, and 30% of these patients survived >20 years. On multivariable analysis, dFLC >180 mg/L and BM plasma cells >10% were independently associated with shorter EFS, whereas BNP >81 pg/mL, troponin I > 0.1ng/mL, and serum creatinine >2.0mg/dL were independently associated with shorter OS. We developed a prognostic score for EFS, which incorporated dFLC >180 mg/L and BMPC% >10% as adverse risk factors. Patients with low-risk (0 factors), intermediate-risk (1 factor), and high-risk (2 factors) disease had median EFS estimates of 5.3, 2.8, and 1.0 years, respectively (p< .001). The 100-day treatment-related mortality rate was 3% in the latest treatment period (2012-2021), and the 25-year risk of t-MDS/AML was 3%. We conclude that HDM/SCT induces durable hematologic responses and prolonged survival with improved safety in selected patients with AL amyloidosis.

Outcomes of Aggressive B Cell Lymphoma Patients with No Evidence of Measurable Disease at the Time of CD19 Chimeric Antigen Receptor T Cell Therapy: The Experience from the CAR T Cell Consortium

Outcomes of Aggressive B Cell Lymphoma Patients with No Evidence of Measurable Disease at the Time of CD19 Chimeric Antigen Receptor T Cell Therapy: The Experience from the CAR T Cell Consortium

De-Escalation of Ptcy Dosing in Matched Allogenic Transplants: A Single Institution Retrospective Study

IntroductionThe role of post-transplant cyclophosphamide (PTCy) in preventing acute GVHD (aGVHD) and chronic GVHD (cGVHD) has been well established in the haploidentical setting (Al-Homsi AS et al., Post-transplant high-dose cyclophosphamide for the prevention of graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21(4):604-611). More recently, several studies are also supporting its use in matched related and unrelated donors (Williams L et al., Post-transplantation Cyclophosphamide: From HLA-Haploidentical to Matched-Related and Matched-Unrelated Donor Blood and Marrow Transplantation. Front Immunol. 2020;11(April):1-7). But as new emerging data are starting to show some toxicities from that regimen, a reevaluation of the optimal PTCy dose is highly valuable (Duléry R et al., Early Cardiac Toxicity Associated with Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation. JACC CardioOncology. 2021;3(2):250-259; Goldsmith et al., Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis. Blood. 2021;137(23):3291-3305).PTCy dose de-escalation in preventing GvHD was also evaluated in a phase I/II study (NCT03983850) with initial results indicating that de-escalation of PTCy (DL2, 25 mg/kg/day given in Days 3−4) may provide a feasible and effective approach in preventing severe aGvHD(McAdams MJ et al., Phase I Study De-Intensifying Exposure of Post-Transplantation Cyclophosphamide (PTCy) after HLA-Haploidentical Hematopoietic Cell Transplantation (HCT) for Hematologic Malignancies. Transplant Cell Ther Off Publ Am Soc Transplant Cell Ther. 2021;27(3): S9-S11). However, this was in the setting of haplo-identical transplants. Currently there are no studies that investigate the safety and efficacy of a lower dose of PTCy in matched allogenic transplants.MethodsWe retrospectively selected 37 consecutive patients who underwent transplant at our center from January 2017 to April 2021. Patients who received a mismatched or haploidentical transplants were excluded. 26 matched sibling or matched unrelated donor transplants were further analyzed. These were divided into 3 cohorts according to GVHD prophylaxis: cohort 1 (No-PTCy) received standard calcineurin inhibitor-methotrexate based GVHD prophylaxis (n=16), cohort 2 (PTCy-50) received PTCy at 50 mg/kg (D+3 and D+4) in combination other immunosuppressive drugs (ISD) (n=6), and cohort 3 (PTCy-25) received PTCy at 25 mg/kg (D+3 and D+4) in combination with other ISD (n=4). The reduced PTCy dosing was based on physician discretion due to various reasons (2 cardiac risk, 1 heavy pre-treatment, 1 unknown).ResultsBaseline characteristics are summarized in table 1. Median follow up for all survivors was 523 days (range, 97-1463) while it was shorter for PTCy cohorts at 152 days (97-534). There were zero grade 3 aGVHD in PTCy groups compared to 12.5% (2/16) in No-PTCy cohort (p=0.30). cGVHD was significantly lower in PTCy-50 and PTCy-25 as compared to No-PTCy (0/6, 0/4, 5/16 respectively, p=0.04). The 100-day treatment-related mortality (TRM) was significantly lower in PTCy-25 as compared to PTCy-50 and No-PTCy (0/4, 2/6, 2/16 respectively, p<0.001). There was no viral reactivation (EBV/CMV) in PTCy-25 as compared to 1/6 in PTCy-50 and 5/16 in No-PTCy (p=0.54). The length of hospital stay (LOS) for transplant and the median days for neutrophil recovery (NR) were shorter in PTCy-25 as compared to PTCy-50 and No-PTCy (25.5 days, 31 days and 28.5 days respectively for LOS, p=0.60; 15.5 days, 22 days and 17.5 days for NR, p=0.87). Although the overall survival (OS) seems to favor PTCy-25 (Figure 1), it is limited by short follow up.ConclusionDe-escalating the dose of PTCy to 25mg/kg x 2 in GVHD prophylaxis regimens appears to be efficacious and safe in patients receiving matched allogenic transplant. Further prospective studies including a larger patient sample and longer follow-up is warranted to investigate lower PTCy dosing in matched transplants over the current standard dosing. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of anti-anaerobic antibiotic activity on graft-versus-host disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients at an institution that utilizes antibiotic cycling.

At our institution, antibiotic cycling for febrile neutropenia is utilized to increase heterogeneity of antibiotic exposure in patients who have undergone an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Development of acute graft-versus-host disease (aGVHD) has been associated with low diversity within stool microbiota. To date, discordant outcomes have been reported implicating anti-anaerobic antibiotic use with the development of aGVHD, and there is currently a lack of published data available in an antibiotic cycled environment. The objective of this study was to determine if there is a difference in the rate of aGVHD in patients who receive anti-anaerobic cycled antibiotics compared with other cycled antibiotics. This was a retrospective, observational study evaluating rates of aGVHD in patients who received antibiotics with anaerobic vs non-anaerobic coverage post-allo-HSCT from January 2008 to January 2018. Univariate and multivariable analyses were performed to assess associations with aGVHD. Secondary outcomes include rate of all stages of aGVHD, progression-free survival, overall survival, 100-day treatment-related mortality (TRM), and 1-year TRM. A total of 273 patients were included in the study. Baseline characteristics were similar between groups, except patients who received anti-anaerobic antibiotics had more unrelated donors (P=.002), were more likely to get myeloablative preparatory regimens (P=.009), had less subtherapeutic calcineurin inhibitor serum concentrations (P=.001), and more often received T-cell depletion (P=.004). The incidence of grades II-IV aGVHD post-HSCT in patients who received anti-anaerobic antibiotics was 32.6% compared with 18.8% in patients who received other antibiotics (P=.015). Multivariable analysis showed that the occurrence of grades II-IV aGVHD was associated with cytomegalovirus reactivation (OR=2.1, 95% CI=1.0-4.5, P=.047), unrelated donors (OR=6.1, 95% CI=2.3-16.6, P<.001), and use of anti-anaerobic antibiotics (OR=2.3, 95% CI=1.1-4.8, P=.021). A 100-day TRM in patients who received anti-anaerobic antibiotics was 9.6% compared with 3.6% in patients who received other antibiotics (P=.046). One-year TRM in patients who received anti-anaerobic antibiotics was 25.2% compared with 13.8% in patients who received other antibiotics (P=.017). There was no statistically significant difference seen between groups in progression free survival or overall survival. Variability in baseline characteristics limits ability to make strong conclusions, but patients who received antibiotics with anaerobic coverage during the first 30days after an allogeneic HSCT appeared to be at an increased risk of developing aGVHD and TRM. Larger well-controlled trials are warranted to further clarify these relationships.

Conditioning with Busulfan Plus Melphalan (Bu-Mel) Results in More Prolonged Progression-Free Survival (PFS) Versus Melphalan (Mel) Alone before Autologous Stem Cell Transplantation (auto-HCT) in Patients with High-Risk Multiple Myeloma (MM): Long-Term Results of a Randomized, Phase 3 Trial

<h3>Background</h3> We previously reported that conditioning with Bu-Mel results in significantly longer PFS compared to Mel alone in patients with newly diagnosed multiple myeloma ([NDMM] Lancet Haematol 2019). Here we report the outcomes of the high-risk patients (based on chromosomal abnormalities as defined by IMWG) enrolled in this trial. <h3>Methods</h3> The primary objective was to compare PFS in NDMM patients who undergo auto-HCT with Bu-Mel versus Mel conditioning. Transplant eligible patients were randomly assigned (1:1) to treatment. Patients in Bu-Mel arm received test dose Bu 32 mg/m2 followed by PK adjusted Bu to achieve a target AUC of 5000 microMol-minute (days -7 to -4) and Mel 70 mg/m2 on days -2 and -1. Patients in Mel arm received Mel 200 mg/m2 on day -2. <h3>Results</h3> Sixty-two patients (Bu-Mel, n=32; Mel, n=30) were identified. Median age at transplant was 61 yrs in the Bu-Mel and 60 yrs in the Mel arm. Sixteen (50%) and 18 (60%) patients were male in the Bu-Mel and the Mel arm, respectively. The R-ISS stage was I in 6 (22%), II in 17 (63%), and III in 4 (15%) of 27 patients in the Bu-Mel arm versus I in 8 (38%), II in 9 (43%), and III in 4 (19%) of 21 patients in the Mel arm, p=0.39. There was no significant difference in the HCT-CI score, induction therapy, response to induction, number of patients receiving maintenance therapy, and other patients, disease, or treatment characteristics between the two treatment groups. The median time to neutrophil engraftment (ANC ≥500) was 11 days and 12 days in the Bu-Mel and Mel arms, respectively, p=0.002. The median time to platelet engraftment (platelet count ≥20K without transfusion support) was 10 days and 12.5 days in the Bu-Mel and Mel arms, respectively, p<0.001. There was no 100-day treatment-related mortality in either arm. Grade II-IV mucositis was seen in 24 (76%) patients in the Bu-Mel and 5 (17%) in the Mel arm, p<0.001. Grade III neutropenic fever was seen in 22 (69%) patients in the Bu-Mel and 9 (30%) in the Mel arm, p=0.005. There was no grade IV toxicity in either arm. The overall response rate (PR or better) at day 90 after auto-HCT was 100% (sCR/CR=34%) in the Bu-Mel arm and 93% (sCR/CR=37%) in the Mel arm, p=0.23. The median follow-up was 41.3 months in the Bu-Mel arm and 36.5 months in the Mel arm. The median PFS was 44.7 months versus 25.7 months in the Bu-Mel and Mel arms, respectively, p=0.044 (Figure 1). The median overall survival (OS) was not reached in either arm, p=0.51 (Figure 2). The three-year PFS & OS rates in the Bu-Mel and Mel arm were 69% & 90%, and 41% & 87%, respectively. In a fitted Bayesian piecewise exponential regression model, treatment with Bu-Mel was associated with superior PFS. <h3>Conclusion</h3> Conditioning therapy with Bu-Mel before auto-HCT yields significantly longer PFS in high-risk myeloma patients compared with Mel alone. Longer follow-up is needed to characterize any OS benefit.

Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis

Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p &lt;0.001, respectively). Primary disease status (p = 0.039); stem cell source (p &lt;0.001); GVHD prophylaxis with ATG (p &lt;0.001); total body irradiation (p &lt;0.001); and conditioning regimen (p &lt;0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p&lt;0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p &lt;0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

Efficacy and safety of autologous stem cell transplantation in patients aged ≥ 65 years with multiple myeloma in the era of novel agents.

Clinical trials evaluating the role of autologous hematopoietic stem cell transplantation (auto-HCT) in multiple myeloma have mostly included patients aged <65 years. Therefore, this study was aimed to evaluate the efficacy and safety of auto-HCT in elderly patients with multiple myeloma in the era of novel agents. We retrospectively analyzed 2056 patients with multiple myeloma, who underwent auto-HCT in 2007-2014 (287 were aged ≥65 years). We evaluated the 100-day treatment-related mortality (TRM) and overall survival (OS) in two groups; elderly patients ( ≥65 years) who underwent auto-HCT compared with younger patients ( <65 years). In the propensity score-matched-pair analysis used to adjust for possible selection bias, the incidence of 100-day TRM between patients aged <65 (0.4%; 95% confidence interval [CI]: 0.0-2.0%) and ≥65 years (1.2%; 95% CI: 0.3-3.1%) showed no statistically significant difference (p = 0.31). The probability of the 5-year OS after transplantation in those aged <65 (62.5%; 95% CI: 58.6-66.1%) and ≥65 (63.5%; 95% CI: 52.2-72.7%) years was also not significantly different (p = 0.56). This study showed that the safety and efficacy of auto-HCT in elderly patients with multiple myeloma in the era of novel agents compared with younger patients were similar.

Toxicity and Outcome Assessment of Concurrent Gabapentin or Pregabalin Administration with High-Dose Melphalan in Autologous Hematopoietic Cell Transplant Patients

Introduction L-type amino acid transporter 1 (LAT1) and 2 (LAT2) are responsible for the transport of large neutral amino acids across the intracellular membrane. These transporters appear to have drug-carrying functionality with certain medications such as gabapentin (GP), pregabalin (PG), melphalan, levodopa, methyldopa, and baclofen. It is likely that concurrent administration of either GP or PG occurs in patients receiving HD-Mel conditioning which could theoretically result in changes in cellular uptake, mucosal injury, and survival. Methods A retrospective review of patients with multiple myeloma who received outpatient HD-Mel from January 2012 to July 2016 was conducted. Patients? 18 years who received melphalan ? 140 mg/m2 were included. Exclusion criteria included concomitant use of levodopa, methyldopa, or baclofen; or deviation from an anti-emetic regimen of steroids, ondansetron, and fosaprepitant. The primary endpoint was rate of mucositis. Secondary endpoints included hospital admission rate, parenteral nutrition (TPN) utilization, patient-controlled analgesia (PCA) initiation, intravenous (IV) opioid requirements, use of topical mucosal agents, use of antidiarrheals, use of rescue anti-emetics, number of days of nausea or vomiting, median daily pain scores, time to neutrophil engraftment, time to platelet-20 engraftment, time to platelet-50 engraftment, 30-day treatment-related mortality (TRM), 100-day TRM, progression-free survival (PFS), and overall survival (OS). Results Eighty patients were enrolled including 30 patients who received concomitant GP/PG and 50 control patients. Rates of mucositis were 59% vs. 52% for grade 1, 24% vs. 19% for grade 2, 7% vs. 10% for grade 3, 10% vs. 19% patients with no mucositis (p = 0.833) in the GP/PG group vs. the control group, respectively. Admission rate was found to be to be 10% in the GP/PG treated group compared with 18% in the control group (p = 0.439). No significant differences in TPN or PCA usage, IV opioid use, topical mucosal agent use, antidiarrheal use, rescue anti-emetic use, days of nausea/vomiting, or pain scores were observed. Time to neutrophil engraftment, platelet-20 engraftment, and platelet-50 engraftment were not significantly different between treatment groups. No patients in the GP/PG treated group and 6% (n = 3) of patients in the untreated group experienced TRM within 100 days (p = 0.288), with similar median PFS and OS. When patients were stratified by GP/PG dose, a correlation with higher doses and lower incidence of mucositis, nausea, vomiting, and pain was observed, although statistical significance was not reached. Conclusion It appears safe to continue GP/PG therapy throughout HD-Mel therapy with no negative outcomes described currently. Larger studies are needed to better characterize the clinical implications of concomitant therapy.

Efficacy and Safety of Autologous Stem Cell Transplantation in Elderly Patients with Multiple Myeloma in the Era of Novel Agents

Introduction : In the past decade, the combination of high-dose melphalan (MEL) and auto-hematopoietic stem cell transplantation (auto-HCT) with novel agents substantially improved the outcomes in younger patients with multiple myeloma. However, the safety and efficacy of auto-HCT in patients aged ≥65 years remain uncertain. Large clinical trials evaluating the role of auto-HCT in multiple myeloma mostly included patients aged Methods: We examined 2,056 patients aged ≥16 years who underwent auto-HCT for multiple myeloma from 2007 to 2014; they were selected based on the following criteria: (1) first auto-HCT with peripheral blood stem cells; (2) use of MEL alone (100, 140, and 200 mg/m2) as a conditioning regimen; and (3) without planned tandem transplantation. A total of 2,056 patients met these criteria, and 287 of them were aged ≥65 years. The era of novel agents was defined as the date of transplantation after December 2006 because bortezomib was approved for public administration in Japan in December 2006. The primary end-point was 100-day treatment-related mortality (TRM), i.e., not myeloma-related or accidental deaths within 100 days after the first auto-HCT, and the secondary end-point was overall survival (OS). To adjust for a selection bias, the 100-day TRM was compared between two age groups ( Results: The median age at transplantation was 66 (range, 65-76) and 57 (range, 18-64) years in the elderly and younger groups, respectively. The number of patients who used 100, 140, and 200 mg/m2 MEL were 17 (1.0%), 71 (4.0%), and 1,681 (95.0%), respectively, in the younger group and 19 (6.6%), 51 (17.8%), and 217 (75.6%), respectively, in the elderly group, with a significant difference (p Conclusion: The 100-day TRM and OS were not significantly different between the younger and elderly patients who underwent auto-HCT for multiple myeloma in 2007-2014. We showed that auto-HCT is safe and effective for treating multiple myeloma in elderly patients, particularly in the era of novel agents. A comparable benefit was observed in elderly patients who underwent auto-HCT for multiple myeloma, highlighting the fact that chronologic age alone should not be used to determine transplantation eligibility. Disclosures Hanamura:CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Kyowa Hakko Kirin Company, Limited: Research Funding; Bristol-Myers Squibb: Other: Lecture fee, Research Funding; Celgene: Other: Lecture fee; Takeda Pharmaceutical Company Limited.: Other: Lecture fee; Fujimoto Pharmaceutical Corporation: Research Funding. Sunami:Sanofi: Research Funding; AbbVie: Research Funding; Daiichi-Sankyo: Research Funding; MSD: Research Funding; Takeda: Research Funding; Bristol-Myers Squibb K.K.: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Ono: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Research Funding; Janssen: Research Funding. Mori:Janssen: Honoraria; Eisai: Honoraria; Japan Blood Products Organization: Honoraria; Shire Japan: Honoraria; Kyowa Hakko Kirin: Honoraria; Ono: Honoraria; Celgene: Honoraria; MSD: Honoraria; Taisho Toyama Pharmaceutical Co: Honoraria; Pfizer: Honoraria; Novartis Pharma: Research Funding; Asahi Kasei: Research Funding; Astella Pharma: Honoraria; CHUGAI: Honoraria; SHIONOGI: Honoraria; Novartis Pharma: Honoraria; MSD: Research Funding. Iida:MSD: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Ono: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Kyowa-Hakko Kirin: Research Funding; Gilead: Research Funding; Sanofi: Consultancy; Teijin Pharma: Research Funding; Toyama Chemical: Research Funding; Astellas: Research Funding; Chugai: Research Funding. Kako:Takeda Pharmaceutical Company Limited.: Honoraria; Takeda Pharmaceutical Company Limited.: Honoraria; Celgene K.K.: Honoraria; Bristol-Myers Squibb: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria. Sawa:Celgene Corporation: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis International AG: Honoraria; CHUGAI PHARMACEUTICAL CO., LTD.: Honoraria; Mundipharma K.K.: Honoraria. Kanda:Dainippon-Sumitomo: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding; Nippon-Shinyaku: Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Taiho: Research Funding; Pfizer: Research Funding; MSD: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Asahi-Kasei: Research Funding; Ono: Consultancy, Honoraria, Research Funding; Sanofi: Research Funding; Novartis: Research Funding; Shionogi: Consultancy, Honoraria, Research Funding; Taisho-Toyama: Research Funding; CSL Behring: Research Funding; Tanabe-Mitsubishi: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Mochida: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Takara-bio: Consultancy, Honoraria. Ichinohe:Celgene: Honoraria; JCR Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria; Alexion Pharmaceuticals: Honoraria; Zenyaku Kogyo Co.: Research Funding; Janssen Pharmaceutical K.K.: Honoraria; Mundipharma: Honoraria; Takeda Pharmaceutical Co.: Research Funding; Taiho Pharmaceutical Co.: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; Repertoire Genesis Inc.: Research Funding; Otsuka Pharmaceutical Co.: Research Funding; MSD: Research Funding; Nippon Shinyaku Co.: Research Funding; Pfizer: Research Funding; Ono Pharmaceutical Co.: Research Funding; Kyowa Hakko Kirin Co.: Research Funding; Eisai Co.: Research Funding; CSL Behring: Research Funding; Chugai Pharmaceutical Co.: Research Funding; Astellas Pharma: Research Funding; Novartis.: Honoraria. Takamatsu:Bristol-Myers Squibb: Research Funding; Ono: Research Funding; Janssen: Honoraria; Celgene: Honoraria, Research Funding. Takami:Chugai: Research Funding; Bristol-Myers Squibb: Research Funding; Kyowa Hakko Kirin: Research Funding.

Improving Treatment Related Mortality over Time - Data from the Non-Observational Trial on Autologous Stem Cell Transplantation in Systemic Sclerosis By the EBMT Autoimmune Diseases Working Party (ADWP)

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease with ongoing high disease related mortality. Three randomized controlled trials proofed efficacy of autologous stem cell transplantation (aHSCT) in patients with severe SSc and superiority over the standard cyclophosphamide pulse therapy. Treatment related mortality is a major point of criticism and different treatment regimen are used in different centers.Methods: This prospective, open, multi-center, non-interventional study of the European Group for Blood and Marrow Transplantation (EBMT) analyzed data for consecutive aHSCT performed in SSc. Every center followed its own local protocol which usually refers to the recent update of the EBMT Guidelines. In order to be eligible for inclusion, patients had to be transplanted for the diagnosis of progressive SSc and aged between 18 and 65 years. Major exclusion criteria were an ejection fraction <40% by cardiac echo, pulmonary arterial hypertension with systolic pulmonary arterial pressure (sPAP) >50mmHg, creatinine clearance <30ml/min, reduced lung function with either FVC <50% or DLCO <30% of predicted values. Concurrent neoplasms, myelodysplasia, severe psychiatric illnesses as well as previously damaged bone marrow had to be ruled out.Progression free survival (PFS) was chosen as primary endpoint. Response to treatment, defined as the number of patients who achieve >25% improvement of the skin thickness, measured by the modified Rodnan Skin score (mRSS; range 0-51) and/or ≥10% improvement in forced vital capacity (FVC) or hemoglobin-adjusted diffusion lung capacity for carbon monoxide (DLCO) and relapse rate as well as safety considerations were secondary endpoints.Results: Between 2013 and 2015, 80 patients from 12 centers were followed for a median of 24.1 (5.97 - 59.8) months. Patients had a median age of 43 years at aHSCT and 70% were female. All patients were mobilized with cyclophosphamide (CYC) with a median of 2g/m2 and granulocyte-colony stimulating factor (GCSF) in 98%. In 45% of transplants stem cells were purified using CD34-positive selection. For conditioning, centers used CYC at 200 mg/kg (50 - 240) in 76 patients (95%) or CYC at 100 mg/kg and thiotepa 10 mg/kg in 4 patients. All patients received additional anti-thymocyte globulin (ATG; different brands were used) over 4-5 days.Progression free survival at 1 year was reached by 83.6% of our patients. Response to treatment at 1 year was achieved by 75% (63.7 - 83.2) and 10.1% relapsed or had further progression despite aHSCT. Figure 1 demonstrates the improvement of skin fibrosis over time. Median mRSS decreased from 24 (2 - 49) at baseline to 13 (0 - 40) at month 12, and 10.5 (0 - 32) at month 24. On multivariate analysis, creatine kinase (CK) levels < 250 U/ml, mRSS <24 and lung crepitation at baseline were significantly associated with response to treatment, but especially CD34-positive selection is a strong positive predictor for response to treatment with a hazard ratio of 2.19 as compared to patients treated with non-selected stem-cell.The 100-day treatment-related mortality for this population was 6.2% (n=5) (CI 2.3 - 13). Three of these 5 patients had a cardiac or cyclophosphamide related event that led to death. During the 24 months of follow up another 3 patients died due to progressive disease, which leads to an overall survival of 91.2% (CI: 85.1 - 97.4) at 2 years.Discussion: Although aHSCT has been proven effective in SSc, we still do not know which regimen is the best. With data from this non-interventional trial we could demonstrate the effectiveness of aHCST in a daily practice setting. Treatment seems to become safer over time with reduction of TRM from 10% in the European phase III Autologous stem cell transplantation international scleroderma trial (ASTIS; JAMA. 2014; 311(24): 2490-8) to 6.2% in our actual study; mainly due to increasing experience of the centers and exclusion of patients with advanced organ damage. Nevertheless indication for aHSCT should also be driven by negative predictive parameters for disease related mortality and it is fairly unlikely to further reduce TRM in these sick patients.We also found a potential value of CD34-selection in these patients. As a retrospective approach demonstrated no benefit to the outcome of SSc patient treated with AHSCT (Bone Marrow Transplant.2016; 51(4): 501-5), these findings have to be confirmed by prospective randomized trials. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Allogeneic stem-cell transplantation for multiple myeloma: a systematic review and meta-analysis from 2007 to 2017

BackgroundDespite recent advances, multiple myeloma (MM) remains incurable. However, the appearance of allogeneic stem cell transplantation (allo-SCT) through graft-versus-myeloma effect provides a potential way to cure MM to some degree. This systematic review aimed to evaluate the outcome of patients receiving allo-SCT and identified a series of prognostic factors that may affect the outcome of allo-SCT.Patients/methodsWe systematically searched PubMed, Embase, and the Cochrane Library from 2007.01.01 to 2017.05.03 using the keywords ‘allogeneic’ and ‘myeloma’.ResultsA total of 61 clinical trials involving 8698 adult patients were included. The pooled estimates (95% CI) for overall survival (OS) at 1, 2, 3 and 5 years were 70 (95% CI 56–84%), 62 (95% CI 53–71%), 52 (95% CI 44–61%), and 46 (95% CI 40–52%), respectively; for progression-free survival were 51 (95% CI 38–64%), 40 (95% CI 32–48%), 34 (95% CI 27–41%), and 27 (95% CI 23–31%), respectively; and for treatment-related mortality (TRM) were 18 (95% CI 14–21%), 21 (95% CI 17–25%), 20 (95% CI 13–26%), and 27 (95% CI 21–33%), respectively. Additionally, the pooled 100-day TRM was 12 (95% CI 5–18%). The incidences of grades II–IV acute graft-versus-host disease (GVHD) and chronic GVHD were 34 (95% CI 30–37%) and 51 (95% CI 46–56%), respectively. The incidences of relapse rate (RR) and death rate were 50 (95% CI 45–55%) and 51 (95% CI 45–57%), respectively. Importantly, disease progression was the most major cause of death (48%), followed by TRM (44%). The results failed to show an apparent benefit of allo-SCT for standard risk patients, compared with tandem auto-SCT. In contrast, all 14 trials in our study showed that patients with high cytogenetic risk after allo-SCT had similar OS and PFS compared to those with standard risk, suggesting that allo-SCT may overcome the adverse prognosis of high cytogenetic risk.ConclusionDue to the lack of consistent survival benefit, allo-SCT should not be considered as a standard of care for newly diagnosed and relapsed standard-risk MM patients. However, for patients with high-risk MM who have a poor long-term prognosis, allo-SCT may be a strong consideration in their initial course of therapy or in first relapse after chemotherapy, when the risk of disease progression may outweigh the transplant-related risks. A large number of prospective randomized controlled trials were needed to prove the benefits of these therapeutic options.

Durable Remission and Survival in Relapsed/Refractory Multiple Myeloma after Allogeneic Hematopoietic Stem Cell Transplantation

Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the setting of refractory multiple myeloma (MM) is still controversial. Although potentially curative in a subset of pts, concerns regarding treatment related mortality (TRM) and graft vs. host disease (GVHD) preclude its universal use. In this study, we evaluated the role of allo-HSCT for pts with relapsed MM.Methods: 110 consecutive pts with relapsed MM underwent allo-HSCT at our institution between 2000 and 2014. The primary objective was to assess progression-free (PFS) and overall survival (OS).Results: Median age at allo-HSCT was 54 (range, 32-71) years and median time from diagnosis to allo-HSCT was 35.7 (range, 8.6 to 228.8) months. Fifty-two (47%) and 49 (45%) pts had standard-risk (SR) and high-risk (HR) cytogenetics at the time of allo-HSCT, respectively. Pts received a median of 5 (range, 1-9) prior chemotherapy regimens and 99 (90%) pts had at least 1 (range, 0-3) prior auto-HSCTs. One hundred one (92%) pts received either a proteasome inhibitor (PI) or an immunomodulatory drug (IMiD) prior to allo-HSCT, with 65 (59%) receiving both. Sixty eight (62%) received allo-HSCT from matched related, 34 (31%) from matched unrelated, 5 (4%) from cord blood, and 3 (3%) from mismatched donors. Preparative regimen was fludarabine/melphalan-based in 88 (80%) and fludarabine/busulfan-based in 16 (15%) pts. Median time to neutrophil and platelet engraftment was 12 (range, 8-30) and 13 (range, 0-81) days, respectively. Ten pts died of non-relapse causes within 100 days (100-day TRM: 9%) and 21 (19%) within 1 year. Grade 1-4 acute GVHD was seen in 50 (45%) and cGVHD in 35 (32%) pts, respectively. Eighteen (16%) achieved a CR, 26 (23%) a VGPR and 38 (34%) achieved a PR, with an overall response rate of 73%. With a median follow up of 41.9 months (range, 6.4 to 172.9) in surviving pts, 1- and 2-year PFS were 23% and 15%, respectively (Fig 1). One and 2-year OS were 50% and 32%, respectively (Fig 2). HR cytogenetics at allo-HSCT were associated with a significantly shorter 2-year PFS (6% for HR vs. 23% for SR; p=0.007) and OS (p=0.01). A response <PR after allo-HSCT was also associated with significantly shorter 2-year PFS (p<0.001) and OS (p<0.001).Conclusions: Allo-HSCT is associated with durable remission and survival in approximately 15% of heavily pretreated pts with relapsed/refractory MM. Novel, more effective approaches are needed for patients with HR cytogenetic abnormalities. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Outcomes of allogeneic hematopoietic stem cell transplantation for lymphomas: a single-institution experience.

IntroductionAllogeneic hematopoietic stem cell transplantation offers the opportunity for extended survival in patients with Hodgkin's and non-Hodgkin lymphomas who relapsed after, or were deemed ineligible for, autologous transplantation. This study reports the cumulative experience of a single center over the past 14 years aiming to define the impact of patient, disease, and transplant-related characteristics on outcomes.MethodsAll patients with histologically confirmed diagnosis of Hodgkin's or non-Hodgkin lymphomas who received allogeneic transplantation from 2000 to 2014 were retrospectively studied.ResultsForty-one patients were reviewed: 10 (24%) had Hodgkin's and 31 (76%) had non-Hodgkin lymphomas. The median age was 50 years and 23 (56%) were male. The majority of patients (68%) had had a prior autologous transplantation. At the time of allogeneic transplantation, 18 (43%) patients were in complete and seven (17%) were in partial remission. Most (95%) patients received reduced-intensity conditioning, 49% received matched sibling donor grafts, 24% matched-unrelated donor grafts, and 27% received double umbilical cord blood grafts. The 100-day treatment-related mortality rate was 12%. After a median duration of follow up of 17.1 months, the median progression-free and overall survival was 40.5 and 95.8 months, respectively. On multivariate analysis, patients who had active disease at the time of transplant had inferior survival.ConclusionsAllogeneic transplantation results extend survival in selected patients with relapsed/refractory Hodgkin's and non-Hodgkin lymphomas with low treatment-related mortality. Patients who have active disease at the time of allogeneic transplantation have poor outcomes.

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the 'Head Start' trials, 1991-2009.

Since 1991, three sequential prospective clinical trials have been conducted by the 'Head Start' (HS) Consortium in which young children with newly-diagnosed malignant central nervous system (CNS) tumors were treated with induction chemotherapy followed by single-cycle marrow-ablative chemotherapy and autologous hematopoietic rescue as a means of improving disease cure rate and quality of survival through avoidance (<6 years old at diagnosis) or reduction (6-10 years old) of brain irradiation. Bone Marrow (HS I) or filgrastim-mobilized peripheral hematopoietic cells (HS II and III) were obtained following recovery from the first and/or second induction cycles. Radiotherapy was administered following all chemotherapy only for patients with residual tumor following completion of induction or with age greater than 6 years at diagnosis. Two hundred and twenty-six children were enrolled on three consecutive HS trials with primary malignant CNS tumors and underwent marrow-ablative chemotherapy. The 100-day treatment-related mortality (TRM) steadily declined as did grade IV transplant-related oropharyngeal mucositis. Factors most likely associated with the decrease in TRM and morbidity are increasing experience with the marrow-ablative chemotherapy regimen combined with improved leukapheresis and post-reinfusion supportive care techniques, contributing toward improved overall survival.

Early Versus Delayed Autologous Stem Cell Transplantation and Interferon Maintenance in Multiple Myeloma: Single-Center Experience of 18 Years

BackgroundAutologous stem cell transplantation (ASCT) has become the mainstay of 1st-line treatment in younger patients with multiple myeloma (MM), but statistical confirmation of its superiority over other therapies, especially in the era of novel agents, is still lacking. MethodsWe reviewed the results of all 548 myeloma ASCTs performed in our institute over the past 18 years. ResultsMore than one-half of the patients had access to novel agents before their transplantations. Although the age of the transplanted patients increased significantly over the years, treatment-related mortality (TRM) was remarkably low, especially in 1st-line transplanted patients (100-day TRM, 0.3%). The median overall survival (OS) of the entire cohort was 98.4 months. Patients transplanted within 12 months from the start of their therapy had significantly better responses than those having delayed ASCT (complete response rate, 58.1% vs 46.8%; P = .016) and significant post-ASCT progression-free survival (PFS) benefit (30.2 [26.1–34.3] mo vs 23.3 [16.8–29.8] mo; P = .036), but we found no significant overall survival difference. The results were similar in patients treated with or without novel agents before ASCT. During a period of time, interferon maintenance was our standard approach to post-ASCT maintenance. Our analysis showed not only a significant PFS advantage with interferon, but also a highly significant overall survival benefit (150.4 [105.1–195.8] mo vs 86.1 [72.5–99.7] mo; P = .003). ConclusionsOur findings demonstrate that delayed ASCT can be feasible in selected patients.

Highly Prolonged Overall Survival Following Reduced Intensity Allogeneic Stem Cell Transplantation for Multiple Myeloma in the New Drugs Era

e282 survival (OS) and progression-free survival (PFS) were 69% (95% CI:6-55%) and 35% (95% CI:6-22%), respectively (Figure 1). On multivariate analysis, chemorefractory disease at alloHCT was associated with an inferior PFS (Hazard risk [HR] 5.75 [95% CI:2.32-14.23]), inferior OS (HR 5.19 [95% CI:2.05-13.14]), higher toxicity related mortality (TRM, HR 6.60 [95% CI: 1.1139.02]) and higher RI/POD (HR 4.04 [95% CI: 1.07-15.21]). Being younger than 55 years emerged as a protective factor for both PFS (HR0.29 [95%CI:0.14-0.60]) and OS (HR 0.29[0.01-0.10]). Chronic GVHD conveyed a higher TRM (HR 1.15 [95%CI:1.021.30]) but not a reduced RI/POD. Conclusion: Our retrospective data show that RIC alloHCT is a safe and effective therapeutic option in MM patients, allowing long survival outcomes even in heavily pretreated patients. Figure 1 OS (A) and PFS (B) of the whole study population 15th International Myeloma Workshop, September 23-26, 2015 PO-349 Durable Remission and Survival in Relapsed/Refractory Multiple Myeloma After Allogeneic Hematopoietic Stem Cell Transplantation A.M. Cornelison, R.M. Saliba, S. Ahmed, Y. Nieto, Q. Bashir, N. Shah, S. Parmar, K. Patel, C. Hosing, U. Popat, E. Shpall, R. Champlin, M.H. Qazilbash Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HCT) in the setting of refractory multiple myeloma (MM) is still controversial. Although potentially curative in a subset of pts, 10-15% treatment related mortality (TRM) and chronic graft vs. host disease (cGVHD) preclude its universal use. In this study, we evaluated the role of allo-HCT for pts with relapsed MM. Methods: We identified 110 consecutive pts with relapsed MM who underwent allo-HCT at our institution between 2000 and 2014. The primary objective was to assess progression-free (PFS) and overall survival (OS). Results: Median age at allo-HCT was 54 (range, 32-71) years and median time from diagnosis to alloHCT was 35.7 (range, 8.6 to 228.8) months. Fifty-two (47%) and 49 (45%) pts had standard-risk (SR) and high-risk (HR) cytogenetics (CG) at the time of allo-HCT, respectively. Pts received a median of 5 (range, 1-9) prior chemotherapy regimens and 99 pts (90%) had at least 1 (range, 0-3) prior auto-HCTs. One hundred one(92%) pts received either a proteasome inhibitor (PI) or an immunomodulatory drug (IMiD) prior to allo-HCT, with 65 (59%) receiving both. Sixty eight (62%) received allo-HCT from a matched related, 34 (31%) from a matched unrelated, 5 (4%) from a cord blood, and 3 (3%) from a mismatched donor. Preparative regimen was fludarabine/melphalan-based in 88 (80%) and fludarabine/busulfan-based in 16 (15%) patients. Median time to neutrophil and platelet engraftment was 12 (range, 8-30) and 13 (range, 0-81) days, respectively. Ten pts died of non-relapse causes within 100 days (100-day TRM: 9%) and 20 (18%) within 1 year. Grade 1-4 acute GVHD was seen in 50 (45%) and cGVHD in 35 (32%) pts, respectively. Eighteen (16%) achieved a CR, 26 (23%) a VGPR and 38 (34%) achieved a PR, with an overall response rate of 73%. With a median follow up of 11.4 months (range 0.3 to 164) in all pts, and 32.7 months (range 3.6 to 164.3) in surviving pts, 1and 2-year PFS were 24% and 16%, respectively. Similarly, 1and 2-year OS were 52% and 32%, respectively. HR CG at allo-HCT and a response <PR after allo-HCT were associated with significantly shorter PFS (p1⁄40.007 and <0.001, respectively) and OS (p1⁄40.01 and <0.001). (Fig 1) Conclusions: Allo-HCT is associated with durable remission and survival in approximately 20% of heavily pretreated patients with relapsed/refractory MM. Patients with HR CG abnormalities and <PR after allo-HCT need more effective approaches.

Durable Remission and Survival in Relapsed/Refractory Multiple Myeloma After Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the setting of refractory multiple myeloma (MM) is still controversial. Although potentially curative in a subset of pts, concerns regarding treatment related mortality (TRM) and graft vs. host disease (GVHD) preclude its universal use. In this study, we evaluated the role of allo-HSCT for pts with relapsed MM. Methods: 110 consecutive pts with relapsed MM underwent allo-HSCT at our institution between 2000 and 2014. The primary objective was to assess progression-free (PFS) and overall survival (OS). Results: Median age at allo-HSCT was 54 (range, 32-71) years and median time from diagnosis to allo-HSCT was 35.7 (range, 8.6 to 228.8) months. Fifty-two (47%) and 49 (45%) pts had standard-risk (SR) and high-risk (HR) cytogenetics at the time of allo-HSCT, respectively. Pts received a median of 5 (range, 1-9) prior chemotherapy regimens and 99 (90%) pts had at least 1 (range, 0-3) prior auto-HSCTs. One hundred one (92%) pts received either a proteasome inhibitor (PI) or an immunomodulatory drug (IMiD) prior to allo-HSCT, with 65 (59%) receiving both. Sixty eight (62%) received allo-HSCT from matched related, 34 (31%) from matched unrelated, 5 (4%) from cord blood, and 3 (3%) from mismatched donors. Preparative regimen was fludarabine/melphalan-based in 88 (80%) and fludarabine/busulfan-based in 16 (15%) pts. Median time to neutrophil and platelet engraftment was 12 (range, 8-30) and 13 (range, 0-81) days, respectively. Ten pts died of non-relapse causes within 100 days (100-day TRM: 9%) and 21 (19%) within 1 year. Grade 1-4 acute GVHD was seen in 50 (45%) and cGVHD in 35 (32%) pts, respectively. Eighteen (16%) achieved a CR, 26 (23%) a VGPR and 38 (34%) achieved a PR, with an overall response rate of 73%. With a median follow up of 41.9 months (range, 6.4 to 172.9) in surviving pts, 1- and 2-year PFS were 23% and 15%, respectively (Fig 1). One and 2-year OS were 50% and 32%, respectively (Fig 2). HR cytogenetics at allo-HSCT were associated with a significantly shorter 2-year PFS (6% for HR vs. 23% for SR; p=0.007) and OS (p=0.01). A response Conclusions: Allo-HSCT is associated with durable remission and survival in approximately 15% of heavily pretreated pts with relapsed/refractory MM. Novel, more effective approaches are needed for patients with HR cytogenetic abnormalities. Download : Download high-res image (95KB) Download : Download full-size image Download : Download high-res image (79KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.

Outcome of Patients with Immunoglobulin Light-Chain Amyloidosis with Lung, Liver, Gastrointestinal, Neurologic, and Soft Tissue Involvement after Autologous Hematopoietic Stem Cell Transplantation

There is limited information on the outcome when organs other than heart or kidneys are involved by immunoglobulin light-chain amyloidosis (AL). We report the outcome of 53 patients with AL with gastrointestinal (GI), peripheral nerve (PN), liver, lung, or soft-tissue involvement, who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) at our institution between 1997 and 2013. The median age at auto-HCT was 56 years (range, 35 to 74). One, 2, 3, or 4 organs were involved in 43%, 22%, 28%, and 4% of patients, respectively. Concurrent cardiac, renal, or both were involved in 24 (45%) patients. Forty-six patients received induction therapy before auto-HCT. The 100-day and 1-year treatment-related mortality (TRM) were 3.8% (n = 2) and 7.5% (n = 4), respectively. Forty-one (80%) patients achieved a hematologic response. Organ response at 1 year after auto-HCT was seen in 23 (57%) of the 40 evaluable patients. With a median follow-up of 24 months, the median progression-free survival and overall survival (OS) were 36 and 73 months, respectively. Auto-HCT was associated with a low TRM, durable organ responses, and a median OS of > 6 years in selected patients with AL and GI, PN, liver, lung, or soft-tissue involvement.

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.