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Increasing numbers of older adults undergo allogeneic stem cell transplantation (SCT) as the only chance of meaningful survival for hematologic malignancies. However, toxicities in vulnerable patients may offset the benefits of SCT. Frailty and abnormal geriatric assessment (GA) prior to SCT have been associated with decreased overall survival in persons aged 60 and older. The purpose of this pilot study was to determine the prevalence of baseline GA deficits and frailty, the prevalence of frailty or death at three and six months after allogeneic SCT, and associations between baseline assessments and the presence of frailty or death post-SCT. We enrolled 50 patients aged 60 years and older and completed a baseline GA including comorbidity, polypharmacy, nutrition, physical performance, functional status, social support, depression and anxiety, and cognition. Frailty was defined as three or more abnormalities of gait speed, grip strength, weight loss, physical activity, and exhaustion, and was assessed at baseline, three months, and six months after SCT. A composite outcome of frailty or death at three months and six months was analyzed. Frailty was present in 11/50 (22%) of patients at baseline. Ten patients did not complete three- month follow-up, and twelve patients did not complete six-month follow-up. Of those with follow-up data, 22 patients (55%) were frail or deceased three months after SCT, and 27 patients (71%) were frail or deceased six months after SCT. Frailty at baseline was not significantly associated with frailty or death at three or six months after SCT. However, the study's small enrollment limits conclusions on these associations. GA deficits and frailty are prevalent in older adult SCT recipients at baseline and after transplant. Future studies should aim for larger enrollment in order to validate associations between these deficits and outcomes, especially survival, functional status, and quality of life following SCT. [ABSTRACT FROM AUTHOR]

• Myeloablative pharmacokinetic-guided i.v. busulfan is safe in older myelofibrosis patients. • It reduced relapse without increasing NRM even in older patients. • Intermediate 2 DIPSS-plus risk has better outcomes than high-risk disease. Optimal conditioning regimens for older patients with myelofibrosis undergoing allogeneic hematopoietic cell transplant are not known. Likewise, the role of dose intensity is not clear. We conducted a nonrandomized, prospective, phase II trial using low-dose, later escalated to high-dose (myeloablative conditioning), busulfan with fludarabine (Bu-Flu) in myelofibrosis patients up to age 74 years. The first 15 patients received i.v. busulfan 130 mg/m2/day on days –3 and –2 ("low dose"); 31 patients received high-dose conditioning, either 100 mg/m2/day (days –5 to –2; n = 4) or pharmacokinetic-guided area under the curve of 4000 μmol/min (days –5 to –2; n = 27). The primary endpoint was day 100 nonrelapse mortality (NRM). Median age was 58 years (interquartile range [IQR], 53-63). Dynamic international prognostic scoring system-plus was intermediate (n = 28) or high (n = 18). Donors were related (n = 19) or unrelated (n = 27). Cumulative incidence of NRM was 9.7% (95% confidence interval [CI], 0-20.3) at day 100 and at 3 years in the high-dose group and 0% in the low-dose group at day 100, which increased to 20% (95% CI, 0-41.9) at 3 years. With a median follow-up of 5.1 years (IQR, 3.8-6), 3-year relapse was 32.3% (95% CI, 15.4-49.1) in high dose versus 53.3% (95% CI, 26.6-80.1) in low dose. Event-free survival was 58% (95% CI, 43-78) versus 27% (95% CI, 12-62), and overall survival was 74% (95% CI, 60-91) versus 60% (95% CI, 40-91). In multivariate analysis, high-dose busulfan had a trend toward lower relapse (hazard ratio,.44; 95% CI,.18-1.07; P =.07), with no impact on NRM. Intensifying the Bu-Flu regimen using pharmacokinetic-monitoring appears to be promising in reducing relapse without increasing NRM. [ABSTRACT FROM AUTHOR]

The impact of Janus kinase (JAK) 1/2 inhibitor therapy before allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into 5 groups: (1) clinical improvement (n = 23), (2) stable disease (n = 31), (3) new cytopenia/increasing blasts/intolerance (n = 15), (4) progressive disease: splenomegaly (n = 18), and (5) progressive disease: leukemic transformation (LT) (n = 13). Overall survival (OS) at 2 years was 61% (95% confidence interval [CI], 49% to 71%). OS was 91% (95% CI, 69% to 98%) for those who experienced clinical improvement and 32% (95% CI, 8% to 59%) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors ( P = .03), dynamic international prognostic scoring system score ( P = .003), and donor type ( P = .006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, 2 patients developed serious adverse events necessitating delay of HCT and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days before conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplantation outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy before HCT were particularly encouraging, and need further prospective validation. [ABSTRACT FROM AUTHOR]

The treatment of patients with chronic myelomonocytic leukemia (CMML) with transplant has not been optimized. We retrospectively reviewed the data for 83 consecutive patients with CMML (47 with CMML-1/2 and 36 with CMML progressed to acute myeloid leukemia) who received an allogeneic stem cell transplant (allo-SCT) at our institution between April 1991 and December 2013 to identify factors associated with improved survival and determine whether treatment with hypomethylating agents before transplant improves progression-free survival (PFS). The median age of the cohort was 57 years. Seventy-eight patients received induction treatment before transplant, with 37 receiving hypomethylating agents and 41 receiving cytotoxic chemotherapy. Patients treated with a hypomethylating agent had a significantly lower cumulative incidence of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; P = .03), whereas treatment-related mortality at 1 year post-transplant did not significantly differ between the groups (27% and 30%, respectively; P = .84). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a hypomethylating agent (43%) than in those treated with other agents (27%; P = .04). Our data support the use of hypomethylating agents before allo-SCT for patients with CMML to achieve morphologic remission and improve PFS of these patients. Future studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with myelofibrosis (MF). Bone marrow (BM) morphologic evaluation of myelofibrosis following allo-HSCT is known to be challenging in this context because resolution of morphologic changes is a gradual process. We compared BM samples of patients with myelofibrosis who underwent first allo-HSCT and achieved molecular remission by day 100 with BM samples of patients who continued to have persistent molecular evidence of disease following allo-HSCT. The study group included 29 patients: 17 primary MF, 7 post-polycythemia vera (PV) MF, and 5 post-essential thrombocythemia (ET) MF. In this cohort there were 18 JAK2 p.V617F, 8 CALR ; 1 MPL , and 2 patients had concurrent JAK2 p.V617F and MPL mutations. The control group included 5 patients with primary MF, one with post-PV MF, one with post-ET MF (5 JAK2 p.V617F; 2 CALR). Following allo-HSCT, both groups showed reduction in BM cellularity and number of megakaryocytes. The study cohort also less commonly had dense megakaryocyte clusters and endosteal located megakaryocytes and showed less fibrosis. There was no statistical difference in BM cellularity, presence of erythroid islands, degree of osteosclerosis, or megakaryocyte number, size, nuclear lobation, presence of clusters or intrasinusoidal location. Following allo-HSCT at 100 days, morphologic evaluation of BM in patients with MF cannot reliably predict persistence versus clearance of molecular evidence of MF. Disappearance of BM MF, dense megakaryocyte clusters, and endosteal localization of megakaryocytes are suggestive of disease response. • Reversal of the bone marrow morphologic features of MF often lags behind following allo-HSCT and may create diagnostic challenges in disease surveillance. • It was impossible reliably to predict whether an individual patient has achieved a complete molecular remission based on morphologic examination of bone marrow at day 100 post allo=HSCT. • The disappearance of high-grade bone marrow fibrosis, large clusters of megakaryocytes, and endosteal localization of megakaryocytes are reassuring findings, suggestive of disease response. • Persistence of hypercellularity, increased numbers of megakaryocytes, the presence of intrasinusoidal megakaryocytes, and osteosclerosis should not be interpreted as a lack of response to allo-HSCT or disease recurrence. [ABSTRACT FROM AUTHOR]

Despite the advances made in treatment of myelofibrosis over the past decade and approval of Janus kinase (JAK) inhibitors, allogeneic stem cell transplantation (allo-SCT) remains the only curative intervention and should be considered for all eligible patients with intermediate- and high-risk disease. Using a cutoff value of 83% for low CD3 SP + sp chimerism and 95% for low CD33 SP + sp chimerism, 49% and 17% developed mixed lymphoid and MMC chimerism, respectively. Blood Cancer J. 10, 2020, 36 13 HJ Deeg, RB Salit, T Monahan, Early mixed lymphoid donor/host chimerism is associated with improved transplant outcome in patients with primary or secondary myelofibrosis. [Extracted from the article]

Abstract: More active high-dose chemotherapy (HDC) regimens are needed for refractory Hodgkin''s lymphoma (HL). We report a cohort analysis of 180 consecutive patients with primary refractory or poor-risk relapsed HL treated with busulfan-melphalan (Bu-Mel) (n = 39), gemcitabine-busulfan-melphalan (Gem-Bu-Mel) (n = 84), or BEAM (BCNU, etoposide, ara-C, melphalan; n = 57) between 2005 and 2010. Their pre-HDC positron emission tomography (PET) scans were interpreted prospectively. Despite more prevalent poor-risk features in the Gem-Bu-Mel cohort, such as PET-positive tumors at HDC, tumors growing at HDC, extranodal disease, or bulky tumors at prior relapse, this cohort had improved outcomes compared with the Bu-Mel and BEAM cohorts, with event-free survival (EFS) rates of 57%, 33%, and 39%, respectively (P = .01), at median follow-up of the whole population of 36 months (range, 3 to 72). Their respective overall survival (OS) rates were, respectively, 82%, 52%, and 59% (P = .04). Secondary acute myelogenous leukemia was seen in 5 patients after BEAM but was not seen in Gem-Bu-Mel and Bu-Mel cohorts (P = .004). Multivariate analyses showed independent adverse effects of an HDC regimen different from Gem-Bu-Mel (hazard ratio [HR] for EFS = 2.3, P = .0008; HR for OS = 2.7, P = .0005), positive PET at HDC (HR for EFS = 2.2, P = .004, HR for OS = 3.1, P = .0001), and >1 previous salvage line (HR for EFS = 1.9, P = .008, HR for OS = 1.8, P = .07). Gem-Bu-Mel improved outcomes in this cohort analysis of patients with refractory/poor-risk relapsed HL and merits evaluation in randomized phase III trials. [Copyright &y& Elsevier]

Abstract: Risk stratification is important to identify patients with acute myelogenous leukemia (AML) who might benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission. We retrospectively studied 150 patients with AML and diagnostic cytogenetic abnormalities who underwent myeloablative allo-HSCT while in first complete remission to evaluate the prognostic impact of persistent cytogenetic abnormalities at allo-HSCT. Three risk groups were identified. Patients with favorable/intermediate cytogenetics at diagnosis (n = 49) and patients with unfavorable cytogenetics at diagnosis but without a persistent abnormal clone at allo-HSCT (n = 83) had a similar 3-year leukemia-free survival of 58%-60% despite the higher 3-year relapse incidence (RI) in the latter group (32.3%, versus 16.8% in the former group). A third group of patients with unfavorable cytogenetics at diagnosis and a persistent abnormal clone at allo-HSCT (n = 15) had the worst prognosis, with a 3-year RI of 57.5% and 3-year leukemia-free survival of only 29.2%. These data suggest that patients with AML and unfavorable cytogenetics at diagnosis and a persistent abnormal clone at allo-HSCT are at high risk for relapse after allo-HSCT. These patients should be considered for clinical trials designed to optimize conditioning regimens and/or to use preemptive strategies in the posttransplantion setting aimed at decreasing RI. [Copyright &y& Elsevier]

Lenalidomide is an agent that has shown great activity in patients with multiple myeloma (MM). However, studies have suggested that this drug negatively affects subsequent stem cell collection. To investigate whether lenalidomide impairs stem cell mobilization and collection, we reviewed data for patients with MM who underwent mobilization with filgrastim. Predictors of mobilization failure were evaluated using logistic regression analysis. In 26 (9%) of 302 myeloma patients, stem cell mobilization failed. Mobilization failed in 25% of patients who had previously received lenalidomide, compared with 4% of patients who had not received lenalidomide (P < .001). In a multivariate analysis, prior lenalidomide use (odds ratio: 5.9; 95% confidence interval [CI]: 2.4-14.3) and mobilization more than 1 year after diagnosis (odds ratio: 4.6; 95% CI: 1.9-11.1) were significantly associated with failed mobilization. Twenty-one of 26 patients in whom mobilization with filgrastim failed underwent remobilization with chemotherapy and filgrastim; in 18 (86%) of these 21 patients, stem cells were successfully mobilized and collected. In patients with multiple myeloma, prior lenalidomide therapy is associated with failure of stem cell mobilization with filgrastim. Remobilization with chemotherapy and filgrastim is usually successful in these patients. [Copyright &y& Elsevier]

Traditionally, pre-transplant conditioning regimen is given over 4-6 days before hematopoietic cell transplant (HCT). Delivering higher dose chemotherapy preparative regimen over a longer time period has not been tested previously. We hypothesized that the delivery of myeloablative dose of busulfan over a 3-week period may reduce toxicity and non-relapse mortality (NRM), without affecting relapse, and tested this in a prospective phase II study. Patients between 18 and 70 years of age with hematological malignancies and adequate organ function, with 8/8-HLA matched related or unrelated donor were eligible. They received a fixed dose of busulfan 80mg/m2 as outpatient on days -20 and -13. Then, fludarabine 40mg/m2 was given on days -6 to -2 followed by busulfan dosed to achieve target area under the curve (AUC) of 20,000 mol/min for the whole course based on pharmacokinetic studies. GVHD prophylaxis was cyclophosphamide (PTCy) 50mg/kg on days 3 and 4 and tacrolimus. Mycophenolate mofetil (MMF) was added to later unrelated donor recipients. All patients received standard supportive care. The primary endpoint was day 100 NRM. We enrolled 52 patients with a median age of 62 (range, 39-69) years. Almost half (n=25, 48%) had AML or MDS and the other half (n=26, 50%) had had CML or MPD; 1 (2%) had multiple myeloma. Low, intermediate, high and very-high disease risk index (DRI) was present in 3 (6%), 34 (65%), 14 (27%) and 1 (2%). HCT-comorbidity index was ≥3 in 23 (44%) and 1-2 (n=23, 44%). A majority (n=32, 62%) had an unrelated donor. With a median follow up of 14 months (range, 3-23), NRM at day 100 was 1.9% (n=1) and 8% (95% CI, 0-15) at 1 year. Overall survival, progression-free survival and relapse at 1-year were 83% (95% CI, 73-95%), 78% (95% CI, 67-91%), and 14% (95% CI, 4-24%), respectively [Table]. There were no graft failures. The median time to neutrophil engraftment was 17 days (range, 13-33) and that of platelets (≥ 20K/µL, n=45) was 24 days (range, 9-266). Day 100 grade II-IV and III-IV acute GVHD rates were 37% (95% CI, 23-50%) and 6% (95% CI, 0-12%), respectively; 1-year chronic GVHD and extensive chronic GVHD rates were 9% (95% CI, 0-17%) and 7% (95% CI, 0-14%), respectively. Overall survival at 1-year differed significantly among patients with low/intermediate DRI (94%; 87-100%) and those with high/very high DRI (53%; 31-91%), P=0.001. Myeloablative fractionated busulfan regimen with PTCy GVHD prophylaxis is feasible in older patients, has low incidence of severe acute GVHD, chronic GVHD, and NRM and results in promising overall survival. [ABSTRACT FROM AUTHOR]

Older patients undergoing allogeneic stem cell transplant (SCT) have inferior outcomes. They have limited physiological reserves, which makes them more susceptible to toxic effects of conditioning regimens. Supportive care directed at maintaining and augmenting their limited functional reserve may reduce non-relapse mortality (NRM). We studied impact of a multidisciplinary supportive care and prehabilitation program (ER-SCT) and compared one-year NRM with a historical control group. Between 1/1/15 and 9/30/18, 204 patients ≥ 65 years old underwent allogeneic SCT at our institution. ER-SCT program started on 10/1/17 and 57 of 64(89%) eligible patients participated during the first year. All 64 patients were included in the ER-SCT cohort, while patients treated between 1/1/15-9/30/17 were in the control group. ER-SCT program consisted of a prehabilitation phase prior to admission. Patients were evaluated by a multidisciplinary team consisting of a geriatrician, physical medicine and rehabilitation physician, physical therapist, occupation therapist, dietician, nurse, and a pharmacist specializing in SCT. Preexisting chronic conditions were optimized and recommendations were made for nutrition, exercise, and coping strategies. During hospitalization, fluid usage and medication choice / doses were optimized for older patients to prevent side effects such as fluid overload and delirium. Physical therapy, occupational therapy and nutrition counselling was continued. The team continued to follow and intervene as needed after discharge from the hospital. Median age was 68 (65-79) with 36 (18%) patients >than 70 years. Diagnoses included AML 96 (47%), MDS 57(28%), MPD 26 (13%), ALL 8(4%), and other 17 (8%). 103 (51%) had high or very high disease risk index (DRI). HCT-CI score was >3 in 80 (39%). Donor types included 127 (62%) matched unrelated, 57(28%) matched related and 20(10%) haploidentical. The NRM at 1 year was 13% in ER-SCT cohort vs 26% (p=0.03) in the control cohort. Multivariate analysis adjusting for GVHD prophylaxis and conditioning regimen, age, DRI, HCT-CI, donor type and graft source showed that ER-SCT HR=0.4 (0.2-0.9, P=0.02), comorbidity score < 4 HR 0.5 (0.3-0.9, P=0.02) and matched related donor HR 0.2 (0.1-0.7, P=0.008) were associated lower with NRM. Although the data from this retrospective sequential cohort analysis cannot be conclusive, they do suggest that a multidisciplinary supportive care program (ER-SCT) may reduce NRM in older patients undergoing allogeneic SCT. [ABSTRACT FROM AUTHOR]

• Brain volume loss may accelerate for months after immunosuppression and HCT for RRMS. • Participants with Gd+ lesions had higher rates of accelerated grey-matter volume loss. • Baseline T1-weighted MRI lesion volumes were associated with white-matter volume loss. • Over the long-term, adequate immunosuppression and HCT may reduce BVL rates. Brain volume loss (BVL) is commonly observed after high-dose immunosuppression and autologous hematopoietic cell transplantation (HDIT/HCT) for treatment of multiple sclerosis (MS). To better understand the mechanisms of underlying BVL associated with this treatment, we characterized the time courses of whole-brain (WB), grey-matter (GM) and white-matter (WM) volume loss in relapsing-remitting MS (RRMS) patients who received BEAM-based HDIT/HCT. We used Jacobian integration to measure MRI-based WB, GM and WM volume changes up to 5 years after transplant in twenty-four RRMS participants who underwent BEAM-based HDIT/HCT. Using a two-piecewise mixed-effects model, we estimated the short-term (baseline to 1 year) and long-term (beyond 1 year) rates of BVL after HDIT/HCT. We also compared the rates based on the presence of gadolinium-enhancing lesions at baseline, and the maintenance of event-free survival during follow-up. On average, accelerated short-term BVL of -1.37% (SE: 0.21), -0.86% (SE: 0.28) and -2.18% (SE: 0.26) occurred in WB, GM and WM, respectively. Baseline T1-weighted MRI WM lesion volume was a significant predictor in the WB (short-term) and the WM (short-term and long-term). The average rates of BVL after the initial acceleration were -0.22%/y (SE: 0.10), -0.13%/y (SE: 0.11) and -0.36%/y (SE: 0.11) in the WB, GM and WM, respectively. Participants with gadolinium-enhancing lesions at baseline had significantly higher short-term rates of GM (-1.56% vs. -0.27%, p = 0.01) and WB volume loss (-1.94% vs. -0.81%, p = 0.006) at 1 year follow-up as compared to those without gadolinium-enhancing lesions. WM volume loss was not significantly different (-2.59% vs. -1.66%, p = 0.16). Participants who maintained event-free survival had similar rates of BVL compared to those who did not. BVL may accelerate for months after HDIT/HCT. However, over the long-term, adequate HDIT/HCT may reduce BVL rates to those similar to normal aging at the WB level. [ABSTRACT FROM AUTHOR]

Background Post transplant cyclophosphamide (PTCy), tacrolimus, and MMF GvHD prophylaxis makes transplantation from haploidentical donors feasible without T cell depletion. In matched donor transplant recipients, cumulative incidences of grades II-IV acute, grades III-IV acute, and chronic GVHD were 51%, 15%, and 14%, respectively when single agent PTCy was used (Kanakry et al JCO 2014 32:3497-3505). However; as a single agent it was inferior to tacrolimus and methotrexate in another study (Alousi etal BBMT 2015, 906-912). We therefore hypothesized that addition of tacrolimus to PTCy may be needed to prevent severe acute GVHD and improve transplant outcomes. Methods All patients with AML undergoing first allogeneic transplant from matched sibling or at least 9/10 matched unrelated donor between 1/1/2011 to 4/30/2018 were eligible for this retrospective study if they received a melphalan or timed sequential busulfan (course AUC 20,000 umol/min) based conditioning regimen. GVHD prophylaxis consisted of tacrolimus and methotrexate 5mg/m2 on day 1, 3, 6, and 11 in the Tac/MTX cohort (n=140); and cyclophosphamide 50mg/kg given on days 3 and 4 and tacrolimus in the PTCy cohort (n=76). Results Patient characteristics were similar in both cohorts except that patients in PTCy cohort were younger with a median age of 59 years versus 63.5 years (P<0.001) and more likely to be in CR-57% v/s 41% (P=0.03). Outcomes and results of univariate analysis are summarized in Table1. Conclusion Tacrolimus and PostCy based GVHD prophylaxis reduces severe GVHD and improves survival. [ABSTRACT FROM AUTHOR]

Myeloablative conditioning can be given safely to older patients by simply administering busulfan over a longer period (fractionated busulfan regimen) than the standard four day regimen. (Popat et al Lancet Haematology 2018). Subsequently, we added post-transplant cyclophosphamide (PTCy) GVHD prophylaxis to our fractionated regimen with a hypothesis that it will reduce GVHD and improve outcomes. Herein, we report the results of our retrospective analysis comparing outcomes of patients with AML who received fractionated busulfan myeloablative conditioning and PTCy versus standard tacrolimus (Tac) and methotrexate (Mtx) GVHD prophylaxis. Patients with AML between 18-70 years of age with adequate organ function and 8/8-HLA matched related or unrelated donor, who were treated on 4 consecutive protocols using fractionated busulfan were included in the analysis. All patients received two fixed doses of busulfan 80mg/m2 as outpatient either on days -13 and -12, or on days -20 and-13 followed by busulfan on day -6 to -3 dosed to achieve target area under the curve (AUC) of 20,000 mol/min for the whole course based on pharmacokinetic studies. Fludarabine ± cladribine were given on day -6 to -3. GVHD prophylaxis was PTCy 50mg/kg on days 3 and 4 and Tac ± mycophenolate mofetil in PTCy cohort (n=53), or standard Tac+ Mtx (n=53). Patients in both the cohorts were matched 1:1 by propensity score. Baseline characteristics were similar between the PTCy and Tac/Mtx cohorts. The median age was 60 (range, 18-70) and 58 (range, 24-70) years, respectively, (P=0.3). Forty-nine percent were in CR, and 30% had comorbidity index >3 in each arm. Similar proportion of patients had ELN adverse risk in both arms (43% vs 40%, respectively P=0.7). The median follow up was 19 months (range, 3-36) in the PTCy and 46 months (range, 14-73) in Tac/Mtx cohort. Overall survival at 2-year was 78% vs 58% (P=0.03), non-relapse mortality was 6% vs 13% (P=0.2), incidence of grade 3-4 acute GVHD at 1-year was 6% vs 19% (P=0.07) and chronic GVHD at 2-year was 10% vs 29% (P=0.03) [Table 1 and figure 1]. The median time to neutrophil engraftment was prolonged by 3 days (15 vs 12 days; P<0.001) and platelet engraftment by 9 days (22 vs 13 days; P<0.001) in the PTCy cohort. Full donor chimerism at day 30 was noted in 79% vs 28% in the PTCy and Tac/Mtx cohorts respectively, (P<0.001). As compared to Tac/Mtx, PTCy-based GVHD prophylaxis not only reduced severe acute GVHD and chronic GVHD, but also improved overall survival in AML patients up to the age of 70 years who received myeloablative fractionated busulfan conditioning. Prospective randomized trial is warranted to validate these findings. [ABSTRACT FROM AUTHOR]

There is paucity of literature regarding hepatitis C virus (HCV) infection in hematopoietic cell transplant (HCT) recipients. In the study described herein we evaluated several aspects of HCV infection in HCT recipients, including the impact of this infection on cancer status, liver-related outcomes, mortality, and the role of antiviral treatment (AVT), including direct-acting antivirals (DAAs). The medical records of HCV-infected allogeneic and autologous HCT recipients, seen at The University of Texas MD Anderson Cancer Center from August 2009 to November 2015, were reviewed. Patients seen from August 1, 2009 to October 30, 2012 were reviewed retrospectively, whereas those seen from November 1, 2012 to November 30, 2015 were analyzed prospectively in an observational study. Of 434 HCV-infected cancer patients evaluated, 64 underwent 69 HCTs. Most (78%) underwent autologous transplantation. Thirteen percent of patients became HCV-seronegative post-HCT. Compared with patients who did not receive AVT, treated patients had fewer relapses of HCV-associated non-Hodgkin lymphomas (20% versus 86%; P = .015), higher 5-year survival rates (75% versus 39%; P = .02), and a trend toward lower rate of progression to cirrhosis (5% versus 21%; P = .06). AVT discontinuation rate post-HCT was 71% in those receiving IFN-containing regimens and 0% in those receiving DAAs ( P < .01). AVT was effective in 12 of 37 patients (32%) and 11 of 13 patients (85%) receiving IFN-based and DAA regimens, respectively ( P = .003). HCV is an important cause of morbidity and mortality in this population. HCV seropositivity can be lost post-HCT, posing a diagnostic challenge. Treatment of HCV infection in HCT recipients improves both oncologic and hepatic outcomes. These patients can be successfully treated with DAAs. [ABSTRACT FROM AUTHOR]

We investigated the impact of patient and disease characteristics, including cytogenetics, previous therapy, and depth of response, on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with myelodysplastic syndrome (MDS). We analyzed 256 MDS patients who underwent transplantation from a matched related (n = 133) or matched unrelated (n = 123) donor after 2001. Of the 256, 78 (30.5%) did not receive cytoreductive therapy before HSCT; 40 (15.6%) received chemotherapy, 122 (47.7%) received hypomethylating agents (HMA), and 16 (6.2%) received both (chemo+HMA). Disease status at HSCT defined by International Working Criteria was complete remission in 46 (18%) patients. There were significant differences between therapy groups: there were more therapy-related MDS and higher use of matched related donor in the untreated group. The chemotherapy group had higher serum ferritin levels at HSCT. Patients were older and had more high-risk disease by revised International Prognostic Scoring in the HMA group. Despite those differences, transplantation outcomes were similar in patients who were untreated and who received cytoreductive therapy before HSCT. Three-year event-free survival (EFS) was 44.2%, 30.6%, 34.2%, and 32.8% for untreated, chemotherapy, HMA, and chemo+HMA groups, respectively ( P = .50). Multivariate analyses revealed that older age (hazard ratio [HR], 1.3; P = .001); high-risk histologic subtypes, including refractory anemia with excess blasts (HR, 1.5; P = .05) and chronic myelomonocytic leukemia (HR, 2.1; P = .03), high-risk cytogenetics with monosomal karyotype (MK) (HR, 4.0; P < .0001) and high serum ferritin level at HSCT (HR, 1.8; P = .002) were poor prognostic factors for EFS. Bone marrow blast count 5% or higher at HSCT (HR, 1.6; P = .01) and MK (HR, 4.2; P < .0001) were the only prognostic factors for increased relapse incidence after HSCT. Patients with MK represented a poor prognostic group, with 3-year EFS of 11.4% and relapse incidence of 60.9%. In this analysis, various therapy approaches before HSCT did not lead to different transplantation outcomes. Cytogenetics defined by MK was able to identify a very poor prognostic groups that innovative transplantation approaches to improve outcomes are urgently needed. [ABSTRACT FROM AUTHOR]

• This retrospective analysis compares the outcome of patients with newly diagnosed multiple myeloma (NDMM) aged >70 versus ≤70 years (n = 1128). • Age cutoff at 70 years is higher than in most other retrospective studies that performed a similar analysis. • There is an association between age at transplantation with progression-free survival and overall survival of patients with NDMM who underwent autologous hematopoietic stem cell transplantation. In this retrospective analysis, we evaluated the impact of age on the outcome of patients with multiple myeloma who received an autologous hematopoietic stem cell transplantation (auto-HCT) at our institution. A total of 1128 patients were divided into the older (>70 years; 182 [16%]) and the younger (≤70 years; 946 [84%]) groups. Compared with the younger cohort, older patients had a higher International Staging System (ISS) stage (ISS-II, 57 [31%] versus 215 [23%]; ISS-III, 52 [28%] versus 211 [22%]; P =.01), higher use of reduced-dose melphalan as a conditioning regimen (140 mg/m², 59 [32%] versus 29 [3%]; P <.001), and a higher comorbidity index (median, 3 versus 2; P =.01). Nonrelapse mortality at 1 year after auto-HCT was significantly higher in older patients (7 [4%] versus 9 [1%]; hazard ratio [HR], 4.1; P =.005). Complete remission rates after auto-HCT for the older and the younger groups were 41% and 46%, respectively. With a median follow-up of 52 months, the 5-year progression-free survival (PFS) was 24% (95% confidence interval [CI], 17% to 32%) and 37% (95% CI, 33% to 40%) in the older and younger groups, respectively (HR, 1.3; P =.02). Five-year OS for the older and younger groups was 56% (95% CI, 47% to 64%) and 73% (95% CI, 70% to 76%; P <.001), respectively. Older age emerged as one of the predictors of shorter OS but not PFS in the multivariate classification and regression tree analysis. In conclusion, age ≥70 years was associated with shorter PFS and OS in patients with multiple myeloma who underwent an auto-HCT. [ABSTRACT FROM AUTHOR]

• CKS1B gain(1q+)/CDKN2C deletion (1p–) has shorter progression-free survival (PFS) despite propensity score matching. • PFS of 3 copies of 1q+ was longer than ≥4 copies and approached significance • 1q+/1p– was suggestive of being an independent risk factor for survival. The gain/amplification CKS1B gene at chromosome region 1q21 (1q+) is one of the most common genetic aberrations in multiple myeloma (MM). Amplification of CKS1B is frequently associated with the deletion of the CDKN2C gene at chromosome region 1p32 (1p–), which is also associated with inferior outcomes. In this retrospective study, we evaluated the outcomes of patients with 1q+ and/or 1p– after high-dose therapy and autologous hematopoietic cell transplantation (auto-HCT). From January 2006 to December 2015, 1491 newly diagnosed patients with MM underwent upfront high-dose therapy and auto-HCT at our institution. Of those, 899 had the fluorescent in situ hybridization (FISH) data available. FISH was performed at diagnosis and before the start of induction in 686 (76%) patients and after the initiation of induction therapy in 213 (24%) patients. We identified 100 patients with 1q+ and/or 1p– by FISH from the cohort of 899 patients. A control group (n = 287) with diploid cytogenetics and normal FISH panel was selected from the same cohort. From the above 2 cohorts, using a propensity score matched analysis, we identified matched controls for 85 of the 100 patients with 1q+/1p–. Patients were matched for age at auto-HCT, sex, International Staging System stage, induction regimen, creatinine level, disease status at auto-HCT, conditioning regimen, and maintenance therapy. Sixty-seven (79%), 4 (5%), and 14 (16%) patients had 1q+, 1p–, or both 1q+ and 1p–, respectively. There was no significant difference in induction therapy, preparative regimen, or maintenance therapy between the 1q+/1p– and the control group. The median follow-up time for all patients was 29.2 months (range, 0.29 to 84.96). The cumulative incidence of 100-day nonrelapse mortality was 1.2% and 0% for the 1q+/1p– and the control group, respectively. Forty-two patients (50%) in the 1q+/1p– group achieved complete response compared with 40 patients (47%) in the control group. The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 79% for the 1q+/1p– group and 56% and 86% for the control group. Patients in the 1q+/1p– group were at significantly increased risk of progression or death compared to the control group (hazard ratio [HR], 2.21; confidence interval [CI], 1.18 to 4.16; P =.014). No significant association between OS in the 2 groups was observed. The outcome of the 1q+/1p– alone (with no additional high-risk cytogenetics) and the propensity score matched control groups was also compared. Median PFS for the 1q+/1p– alone subgroup was 26.6 months, compared with 38.8 months for the control group (HR, 1.9; CI, 0.9 to 4.08; P =. 09). The median OS had not been reached for the 1q+/1p– alone subgroup and was 81.1 months for the control group (HR, 1.25; CI, 0.3 to 4.6; P =.73). 1q+/1p– abnormalities with amplification of CKS1B and deletion of CDKN2C genes were associated with shorter PFS compared with a propensity score matched group of patients with diploid cytogenetics and normal a FISH panel. The outcomes of 1q+/1p– patients with MM have improved with the use of more effective induction, conditioning, and maintenance therapy compared with historical controls, but we still need more effective therapeutic approaches to fully overcome the negative impact of 1q+/1p–. [ABSTRACT FROM AUTHOR]

• Molecular data and MRD at transplant for AML patients significantly influence outcomes. • By incorporating these factors we developed an AML-DRG, which has improved predictive ability compared with the DRI. • A risk model combining patient- and disease-related factors, the HCT-CR, effectively predicts OS for AML. • The AML-HCT-CR divides patients into 4 groups with significantly different post-transplant survival. Molecular data and minimal residual disease (MRD) have been shown to influence outcomes in acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (AHCT). Here we developed and validated a novel AML-specific disease risk group (AML-DRG) and revised our previously developed hematopoietic cell transplant-composite risk (HCT-CR) model by incorporating molecular data and MRD status to predict outcomes of patients with AML. The study included 1414 consecutively treated adult AML patients who received a first AHCT. Patients were randomly assigned into training (n = 944) and validation (n = 470) sets. To develop the AML-DRG model, the coefficient of all significant AML-related variables in multivariable Cox regression analysis in a training dataset was converted into scores, whereas the AML-HCT-CR was the sum of disease-related factors assessed by the AML-DRG model with the addition of weighted scores from patient-related factors. The AML-DRG was developed by assigning the following scores: 1 point to secondary AML, 1 point to the European LeukaemiaNet adverse genetic risk, 2 points to complete remission with MRD positive/unknown, and 4 points to active disease. These scores were used to generate 3 risk groups of the AML-DRG with significantly different overall survivals. By adding the score for significant patient-related factors (HCT-specific comorbidity index/age), we created 4 risk groups of AML-HCT-CR with distinct survival outcomes. Both the AML-DRG and AML-HCT-CR provided significantly better discriminative capacity compared with the disease risk index, European LeukaemiaNet genetic risk model, and cytogenetic risk model. Prognostic models incorporating molecular data and MRD status allow better stratification and improved survival estimates of AML patients post-transplant. [ABSTRACT FROM AUTHOR]

• No 100-day allogeneic transplant-related mortality was found in HIV patients. • The HIV reservoir can no longer be detected with complete donor chimerism. • HIV should not be viewed as a contraindication to transplant. We set out to assess feasibility and safety of allogeneic hematopoietic cell transplant in 17 persons with HIV in a phase II prospective multicenter trial. The primary endpoint was 100-day nonrelapse mortality (NRM). Patients had an 8/8 HLA-matched related or at least a 7/8 HLA-matched unrelated donor. Indications for transplant were acute leukemia, myelodysplasia, and lymphoma. Conditioning was myeloablative or reduced intensity. There was no NRM at 100 days. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 41%. At 1 year, overall survival was 59%; deaths were from relapsed/progressive disease (n = 5), acute GVHD (n = 1), adult respiratory distress syndrome (n = 1), and liver failure (n = 1). In patients who achieved complete chimerism, cell-associated HIV DNA and inducible infectious virus in the blood were not detectable. Blood and Marrow Transplant Clinical Trials Network 0903/AIDS Malignancy Consortium 080 was registered at www.clinicaltrials.gov (no. NCT01410344). [ABSTRACT FROM AUTHOR]

Although bortezomib and rituximab have synergistic activity in patients with lymphoma and both can attenuate graft-versus-host disease (GVHD), the drugs have not been used together in patients undergoing allogeneic stem cell transplantation (alloSCT). In this phase I/II trial, we assessed the safety and activity of bortezomib added to the rituximab (R) plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. Bortezomib (1 to 1.3 mg/m2 per dose) was administered i.v. on days –13, –6, –1, and +2. We performed inverse probability weighting analysis to compare GVHD and survival results with an historical control group that received R-BEAM without bortezomib. Thirty-nine patients were assessable for toxic effects and response. The median age was 54 years. The most common diagnosis was diffuse large B cell lymphoma (41%). Twenty-two patients (56%) and 17 patients (44%) received their transplants from matched related and matched unrelated donors, respectively. The maximum tolerated bortezomib dose was 1 mg/m2. The weighted cumulative incidences of grades II to IV and III or IV acute GVHD were 50% and 34%, respectively; these incidences and survival rates were not significantly different from those of the control group. Median survival was not reached in patients age ≤ 50 years and with a long follow-up time of 60.7 months. The R-BEAM regimen has a survival benefit in lymphoma patients age ≤ 50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD. [ABSTRACT FROM AUTHOR]

• Haploidentical transplants with post-transplantation cyclophosphamide have similar long-term survival as seen with HLA-matched donor transplants. • The FM100 regimen is associated with similar survival as the FM140 regimen for patients with lymphoma, although it is used primarily in older patients. We analyzed 186 patients with lymphoma who underwent allogeneic stem cell transplantation (ASCT) with fludarabine-melphalan (FM) conditioning and different types of donors (25 haploidentical [HD], 98 matched unrelated [MUD], and 63 matched related [MRD]) at our institution between September 2009 and January 2018. Patients received fludarabine 160 mg/m2 (40 mg/m2/day for 4 days) in combination with 1 dose of melphalan 140 mg/m2 (FM140) or 100 mg/m2 (FM100). Engraftment was similar among the 3 groups (92%, 89%, and 98%, respectively; P =.7). The 6-month cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 4% in the HD group, 14% in the MUD group, and 8% in the MRD group (P not significant), and the respective 3-year cumulative incidence of chronic GVHD was 5%, 16%, and 26% (P not significant). The respective 3-year nonrelapse mortality and relapse rates were 31%, 32%, and 10% (HD versus MUD, P =.9; HD versus MRD, P =.02) and 15%, 21%, and 39% (HD versus MUD, P =.4; HD versus MRD, P =.04). At 3 years, progression-free survival (PFS) was 59%, 44%, and 46% (P not significant); overall survival (OS) was 52%, 54%, and 67% (P not significant); and GVHD-free, relapse-free survival was 39%, 31%, and 24% (P not significant). No differences in the 3-year PFS (57% versus 43%; P =.3) and OS (64% versus 58%; P =.7) were seen between patients receiving FM100 and those receiving FM140. Our data demonstrate that in patients with lymphoma, ASCT with HD transplants have similar outcomes as ASCT with HLA-matched transplants, and the FM100 conditioning regimen appears to be at least as effective as the FM140 regimen. [ABSTRACT FROM AUTHOR]

• There was no impact in myeloma survival outcomes by conditioning regimen intensity for allogeneic stem cell transplantation. • Disease status at transplantation is predictive for outcomes. • Patients with complete remission at transplantation have durable responses. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for patients with multiple myeloma, as it provides a graft-versus-myeloma effect alongside a myeloma-free graft. Although reduced-intensity conditioning regimens decrease nonrelapse mortality (NRM), there is a paucity of data with regard to the ideal conditioning regimen in myeloma. We conducted a retrospective comparison of 3 different preparative regimens used for allo-HCT for multiple myeloma at our institution in recent clinical trials: busulfan/fludarabine (BuFlu), fludarabine/melphalan 100 mg/m2 (FM100), and fludarabine/melphalan 140 mg/m2 (FM140). NRM, progression-free survival (PFS) at 3 years, and overall survival (OS) at 3 years were the primary endpoints. Secondary endpoints included time to engraftment, and the incidence of grades II through IV acute graft-versus-host disease and chronic graft-versus-host disease. A total of 73 patients received allo-HCT with these regimens. NRM at 3 years was seen in 3 (21%), 5 (28%), and 6 (24%) patients in the BuFlu, FM100, and FM140 groups, respectively. Three-year PFS in the BuFlu, FM100, and FM140 groups was 16% (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.6 to 2.1), 26% (HR, 0.6; 95% CI, 0.3 to 1.2), and 11% (reference), respectively. Three-year OS in the BuFlu, FM100, and FM140 groups was 39% (HR, 1.1; 95% CI, 0.5 to 2.2), 43% (HR, 0.7; 95% CI, 0.3 to 1.4), and 32% (reference), respectively. High-risk cytogenetics and relapsed disease prior to allo-HCT were found to be independent predictors of inferior OS on multivariate analysis, with a HR of 2.1 (P =.02) and 2.6 (P =.004), respectively. In contrast, the preparative regimen did not emerge as a predictor of PFS or OS. Durable clinical remission can be achieved in 11% to 25% of patients with multiple myeloma with the use of allo-HCT without any significant difference in the safety or efficacy of the conditioning regimen. High-risk cytogenetics and relapsed disease prior to transplant were associated with inferior PFS and OS. [ABSTRACT FROM AUTHOR]

Abstract HLA-DP mismatched allogeneic hematopoietic stem cell transplantation (allo-HCT) is associated with increased risk of aGVHD and decreased risk of relapse with no effects on overall survival (OS). It has been proposed that CMV-reactivation induces expression of HLA-DP molecules on GVHD target tissues by releasing inflammatory cytokines. We hypothesized that the increased GVHD incidence in HLA-DP mismatched allo-SCTs correlates with recipient CMV serostatus or CMV reactivation. In addition, CMV reactivation is associated with increased risk of GVHD with an unknown mechanism. Here, we analyzed the association between HLA-DPB1 and CMV reactivation on cumulative incidence of aGVHD and relapse as well as OS in 613 patients with AML and MDS who underwent matched related or unrelated allo-HCT at MD Anderson Cancer Center from 2005 to 2011. In multivariable analysis, HLA-DPB1 mismatching was associated with increased risk of aGVHD (hazard ratio (HR): 1.53, P < 0.001) independent of CMV serostatus and CMV reactivation. Additionally, HLA-DPB1 mismatching was associated with decreased risk of relapse and no effect on OS. CMV reactivation increased risks of aGVHD (HR: 5.82, P < 0.001) independent of HLA-DP mismatching with no effect on relapse or OS. In conclusion, our data suggests that HLA-DPB1 mismatching and CMV reactivation increase risk of aGVHD independently. [ABSTRACT FROM AUTHOR]

Abstract The outcome of persons > 65 years with acute myeloid leukemia (AML) is poor. A transplant from an HLA-identical sibling or an HLA-matched unrelated donor can cure some of these patients but is associated with a substantial transplant-related mortality and a high relapse risk. We analyzed 185 subjects > 65 years with high-risk AML receiving conventional (n = 42) or reduced-intensity (n = 143) pretransplant conditioning and a transplant from an HLA-identical sibling (n = 66) or a 10/10 loci HLA-matched unrelated donor (n = 119). Two-year survival was 37%. Subjects with serious adverse events during before chemotherapy for their leukemia had a poor outcome after stem cell transplantation. Patients who had active leukemia or measurable residual disease (MRD) before transplantation had a worse outcome. Delayed hematologic recovery after induction or consolidation chemotherapy, high-risk AML genetics, donor–recipient HLA-DRβ3/4/5-DP mismatches, and history of cardiovascular disease were also correlated with survival in multivariate analyses. The 57 MRD-negative patients with few other adverse prognostic factors had an excellent outcome (2-year overall survival, 76%), whereas the 58 patients with detectable leukemia and more than 1 other additional factor fared poorly (2-year overall survival, 8%). These data indicate it is possible to identify persons > 65 years with high-risk AML likely to benefit from an allotransplant. Validation of this prediction is needed. [ABSTRACT FROM AUTHOR]

Highlights • Achieving a hematologic CR was associated with a higher organ response rate and longer OS. • A low β 2 -microglobulin (<3.5) at diagnosis and the use of IMiD/PI as induction therapy emerged as independent predictors of longer OS. • Induction therapy with alkylating agents as well as novel agents (IMiD or PI) followed by high-dose melphalan and auto-HCT was feasible, safe, and effective; our study reports a lower incidence of 100-day and 1-year NRM (3% and 3%, respectively). • There was significantly higher HR after IMiD/PI induction compared with others (either conventional chemotherapy or no induction). Abstract With the availability of immunomodulatory imide drugs (IMiDs) and proteasome inhibitors (PI), most patients with immunoglobulin light chain amyloidosis (AL) receive induction therapy before autologous hematopoietic stem cell transplantation (auto-HCT). In this study we evaluated the type of induction therapy and its impact on the outcome of auto-HCT in AL. We identified 128 patients with AL who underwent high-dose chemotherapy and auto-HCT at our institution between 1997 and 2013. Patients were divided into 3 groups: no induction, conventional chemotherapy (CC)-based induction (melphalan, steroids), and IMiD/PI-based induction (thalidomide, lenalidomide, or bortezomib). The hematologic response (HR) and organ response were defined according to the established criteria. Median age at auto-HCT was 58 years (range, 35 to 75). Twenty patients (15.5%) received no induction, 25 (19.5%) received CC, and 83 (65%) received IMiDs/PIs. One, 2, or 3 or more organs were involved in 90 (70%), 20 (16%), and 18 (14%) patients, respectively. After auto-HCT 12 of 20 (60%), 15 of 24 (62%), and 72 of 83 (87%) assessable patients achieved HR at 100 days in no induction, CC, and IMiD/PI groups, respectively (P =.001). Organ response at 1 year after auto-HCT was seen in 7 of 18 (39%), 14 of 24 (58%), and 37 of 79 (47%) assessable patients in no induction, CC, and IMiD/PI groups, respectively (P =.3). Achieving a hematologic complete response was associated with a significantly higher probability of achieving an organ response (P =.02). After a median follow-up of 26 months, rates of 2-year progression-free survival were 67%, 56%, and 73% in no induction, CC, and IMiD/PI groups, respectively (P =.07; hazard ratio,.5; 95% confidence interval [CI],.3 to 1.1). Rates of 2-year overall survival were 73%, 76%, and 87% in no induction, CC, and IMiD/PI groups, respectively (P =.05; hazard ratio,.4; 95% CI,.2 to.9). On multivariate analysis a low β 2 -microglobulin (P =.01; hazard ratio,.3; 95% CI,.1 to.7) and induction therapy with IMiD/PI (P =.01; hazard ratio,.3; 95% CI,.1 to.7) were associated with a better overall survival. Induction therapy with either CC or IMiDs/PIs is safe and feasible in selected patients with AL. IMiD/PI-based induction is associated with a longer overall survival compared with patients who received no induction or CC before auto-HCT. [ABSTRACT FROM AUTHOR]

We conducted a prospective phase 2 trial of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) with autologous stem cell transplantation (ASCT) in patients with primary refractory or poor-risk relapsed Hodgkin lymphoma (HL) (ie, extranodal relapse or within 1 year of frontline therapy). The trial was powered to detect an improvement in 2-year progression-free survival (PFS) from a historical 50% using a BEAM regimen (carmustine/etoposide/cytarabine/melphalan) to 65%. We compared the study population with all other concurrent patients who were eligible for the trial but instead received the BEAM regimen at our center. No patient received post-ASCT maintenance therapy. The Gem/Bu/Mel trial enrolled 80 patients with a median age of 31 years, 41% with primary refractory HL and 59% with relapsed HL (36% extranodal relapses), and 30% with positron emission tomography (PET)-positive lesions at ASCT. The concurrent BEAM (n = 45) and Gem/Bu/Mel cohorts were well balanced except for higher rates of bulky relapse and PET-positive tumors in the Gem/Bu/Mel cohort. There were no transplantation-related deaths in either cohort. At a median follow-up of 34.5 months (range, 26 to 72 months), Gem/Bu/Mel was associated with better 2-year PFS (65% versus 51%; P  = .008) and overall survival (89% versus 73%; P  = .0003). In conclusion, our data show that Gem/Bu/Mel is safe, in this nonrandomized comparison yielding improved outcomes compared with a concurrently treated and prognostically matched cohort of patients with primary refractory or poor-risk relapsed HL receiving BEAM. [ABSTRACT FROM AUTHOR]

We studied if the inclusion of early post–stem cell transplantation (SCT) minimal residual disease (MRD) assessments improved prognostication in patients with acute myeloid leukemia (AML). Two hundred sixty-nine AML patients in morphological complete remission (CR) who underwent a first SCT were included if they had evaluable pre-SCT MRD assessment by multiparametric flow cytometry. Post-SCT MRD assessments were performed at days +30, +100, and +180. The primary outcome was 1-year relapse incidence (RI). Of 269 patients in CR, 83 (30.8%) had detectable MRD pre-SCT. Post-SCT, during routine disease assessment time points, 9 of 241 evaluable patients (3.7%) at day +30, 6 of 191 evaluable patients (3.1%) at day +100, and 4 of 133 evaluable patients (3%) at day +180 were MRD positive while in CR. MRD positivity at day +30 predicted the highest risk of relapse at 1 year (group 1, 1-year RI 78%). Among MRD-negative patients at day +30, either adverse risk category by European Leukemia Net (ELN) or intermediate risk who were aged ≥60 years and/or pre-SCT MRD-positive represented the intermediate-risk group (group 2, 1-year RI 29%). The remaining patients represented the low-risk group (group 3, 1-year RI 5%). For patients in CR beyond day +30 post-SCT, detectable MRD at any time point predicted impending relapse within 2 months. Early post-SCT MRD assessment—combined with pre-SCT MRD assessment, ELN risk category, and age—improves risk stratification for relapse in AML patients post-transplant. Studies aimed at preventing impending relapse in this high-risk population are urgently needed. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation with HLA-matched donors is increasingly used for older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). It remains unclear if haploidentical stem cell transplantation (haploSCT) is a suitable option for older patients with this disease. We analyzed 43 patients with AML/MDS (median age, 61 years) who underwent a haploSCT at our institution. All patients received a fludarabine-melphalan–based reduced-intensity conditioning regimen and post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Except for 1 patient who had early death, the remaining 42 patients (98%) engrafted donor cells. The cumulative incidences of grades II to IV and III to IV acute GVHD at 6 months were 35% and 5%, respectively, and chronic GVHD at 2 years was 9%. After a median follow-up of 19 months, 2-year overall survival, progression-free survival (PFS), and relapse incidence were 42%, 42%, and 24%, respectively. Best PFS (74% at 2 years) was seen in patients with intermediate-/good-risk cytogenetics, in first or second remission (hazard ratio, .4; P  = .05), and with a younger donor (≤40 years; hazard ratio, .2; P  = .01). In conclusion, these data suggest that haploidentical transplantation is safe and effective for older AML/MDS patients. Disease status, cytogenetics, and younger donor age are predictors for improved survival in older patients receiving a haploidentical transplant. [ABSTRACT FROM AUTHOR]

In this study, we compared transplantation outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with advanced myelodysplastic syndrome (MDS) who received a CD34 + cell-selected and those who received an unmodified allograft. This analysis initially included 181 patients, 60 who received a CD34 + cell-selected transplant and 121 who received an unmodified transplant. Owing to significant differences in disease characteristics, the analysis was limited to patients with <10% blasts before HSCT (n = 145). Two groups were defined: low risk, with low- and intermediate-risk cytogenetics (CD34 + , n = 39; unmodified, n = 46), and high risk: poor and very poor risk cytogenetics (CD34 + , n = 19; unmodified, n = 41). In the low-risk group, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) at 1 year post-transplantation was 18% in the CD34 + subgroup versus 41.3% in the unmodified subgroup ( P  = .015). There were no differences between the subgroups in the incidence of grade III-IV aGVHD. The incidence of chronic graft-versus-host disease (cGVHD) at 3 years in the 2 subgroups was 5.3% and 56%, respectively ( P  < .001). At 3 years post-transplantation, relapse, overall survival (OS), and relapse-free survival (RFS) were similar in the CD34 + and unmodified subgroups: 8.1% versus 19.4% ( P  = .187), 58.5% versus 53.7% ( P  = .51), and 59.5% versus 52.4% ( P  = .448). However, the composite outcome combining extensive cGVHD-free status and relapse-free status (CRFS) at 3 years was 59.5% in the CD34 + group versus 19.2% in the unmodified group ( P  < .001). In the high-risk group, grade II-IV aGVHD at 1 year was 31.6% in the CD34 + subgroup versus 24.4% in the unmodified subgroup ( P  = .752). There were no differences between the subgroups in the incidence of grade III-IV aGVHD. The incidence of cGVHD at 3 years in the 2 subgroups was 0% versus 27.6% ( P  = .013). At 3 years post-transplantation, relapse, OS, RFS, and CRFS in the 2 subgroups were 31.6% versus 69.3% ( P  = .007), 35.5% versus 14.5% ( P  = .068), 31.6% versus 10.7% ( P  = .045), and 31.6% versus 6.1% ( P  = .001), respectively. Cytogenetic abnormalities at diagnosis and transplant type had significant univariate associations with RFS in the high-risk cohort. Only cytogenetics ( P  = .03) remained associated with this outcome in a multivariate model. OS was similar in the 2 transplant groups; however, CRFS was superior in the CD34 + cell-selected transplant group. [ABSTRACT FROM AUTHOR]

Fluid overload (FO) commonly occurs during hospitalization for allogeneic hematopoietic stem cell transplantation. We hypothesized that FO is associated with transplantation outcomes and evaluated this complication in 2 cohorts of patients. FO was graded based on post-transplantation weight gain, symptoms, and need for treatment, scored in real time by an independent team. The first cohort (study cohort; n = 145) underwent haploidentical transplantation for hematologic malignancies following a melphalan-based conditioning regimen. In univariate analysis, factors associated with day +100 nonrelapse mortality (NRM) were FO grade ≥2 (hazard ratio [HR], 15; 95% confidence interval [CI], 4.2 to 55; P  < .001), creatinine >1 mg/dL (HR, 4.7; 95% CI, 1.6 to 14; P  = .005), and age >55 years (HR, 4.5; 95% CI, 1.5 to 13; P  = .008). In multivariate analysis, factors associated with day +100 NRM were FO grade ≥2 (HR, 13.1; 95% CI, 3.4 to 50; P  < .001) and serum creatinine level >1 mg/dL at transplantation admission (HR, 3.5; 95% CI, 1.1 to 11; P  = .03). These findings were verified in a separate cohort (validation cohort) of patients with acute myelogenous leukemia/myelodysplastic syndrome who underwent HLA-matched transplantation with busulfan-based conditioning (n = 449). In multivariate analysis, factors associated with day +100 NRM were FO grade ≥2 (HR, 34; 95% CI, 7.2 to 158; P  < .001) and, in patients with FO grade <2, advanced disease status (HR, 5; 95% CI, 1.1 to 22; P  = .03). A higher NRM translated to significantly poorer 1-year overall survival rates for patients with FO ≥2 than for patients without FO (70% versus 42%, P  < .001 in the study cohort and 64% versus 38%, P  < .001 in the validation cohort). In conclusion, FO grade ≥2 is strongly associated with higher NRM and shorter survival and should be considered an important prognostic factor in transplantation. [ABSTRACT FROM AUTHOR]

We previously showed the safety of using cord blood (CB) expanded ex vivo in cocultures with allogeneic mesenchymal precursor cells (MPC) after myeloablative conditioning with faster recovery of neutrophils and platelets compared with historical controls. Herein, we report the transplantation outcomes of 27 patients with hematologic cancers who received 1 CB unit expanded ex vivo with MPCs in addition to an unmanipulated CB (MPC group) after reduced-intensity conditioning (RIC). The results in this group were compared with 51 historical controls who received 2 unmanipulated CB units (control group). The analyses were stratified for 2 RIC treatment groups: (1) total body irradiation 200 cGy + cyclophosphamide + fludarabine) (TCF), and (2) fludarabine + melphalan  (FM). Coculture of CB with MPCs led to an expansion of total nucleated cells by a median factor of 12 and of CD34 +  cells by a median factor of 49. In patients in whom engraftment occurred, the median time to neutrophil engraftment was 12 days in the MPC group, as compared with 16 days in controls ( P  = .02). The faster neutrophil engraftment was observed in both RIC groups. The cumulative incidence of neutrophil engraftment on day 26 was 75% with expansion versus 50% without expansion in patients who received FM as the RIC regimen ( P  = .03). Incidence of neutrophil engraftment was comparable in MPC and control groups if treated with TCF (82% versus 79%, P  = .40). Transplantation of CB units expanded with MPCs is safe and effective with faster neutrophil engraftment even after RIC regimens. [ABSTRACT FROM AUTHOR]