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Objective: Peripheral T-cell lymphomas (PTCLs) are an uncommon and quite heterogeneous group of disorders, representing only 10%-15% of all non-Hodgkin lymphomas. Although both molecular and clinical studies have increased in recent years, we still have little knowledge regarding real-life practice with PTCLs. In this study, we aimed to investigate the clinical characteristics and treatment outcomes of a large population-based cohort of patients presenting with systemic non-cutaneous PTCL. Materials and Methods: We conducted a multicenter retrospective analysis of 190 patients consecutively diagnosed and treated with non-cutaneous PTCLs between 2008 and 2016. Results: Considering all first-line treatment combinations, the overall response rate was 65.9% with 49.4% complete remission (n=81) and 16.5% partial response (n=27). The 5-year overall survival and eventfree survival rates were significantly different between the transplant and non-transplant groups (p, Amaç: Periferik T-hücreli lenfomalar (PTHL) nadir görülen, oldukça heterojen bir grup hastalıktır ve tüm non-Hodgkin lenfomaların sadece %10-15’ini oluşturur. Son yıllarda hem moleküler hem de klinik çalışmalar artmış olsa da PTHL’ler üzerindeki gerçek yaşam verileri hakkında hala çok az bilgiye sahibiz. Bu çalışmada, sistemik, kutanöz olmayan PTHL hastaları içeren geniş popülasyon tabanlı hasta grubunun klinik özellikleri ve tedavi sonuçlarını araştırmayı amaçladık. Gereç ve Yöntemler: 2008 ve 2016 yılları arasında kutanöz olmayan PTHL tanısı ile tedavi edilen 190 ardışık hastanın geriye dönük analizini gerçekleştirdik. Bulgular: Tüm birinci basamak tedavi kombinasyonları dikkate alındığında, genel yanıt oranı; tam remisyon (n=81) %49,4 ve kısmi yanıt (n=27) %16,5 olmak üzere %65,9 saptandı. Beş yıllık genel ve olaysız sağkalım oranları, transplant ve transplant olmayan gruplar arasında önemli ölçüde farklıydı (sırasıyla, p

Background: Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for hematological disease however can be complicated by relapse or graft failure (GF), for which second-HCT and donor lymphocyte infusions (DLI) are performed. This study aimed to compare outcomes following the two interventions. Methods: We retrospectively investigated 89 patients with relapse or GF after first-HCT, 50 (56%) underwent second HCT and 39 (44%) received (DLI), from June 2011 to September 2020. Results: Median age at intervention was 55 years (19-72). Second-HCT was performed for relapse in 19 patients and for GF in 31 patients (primary GF in 11 and secondary in 20 patients), same donor was used in 25 (50%) patients. DLI was performed for relapse in 20 and for secondary GF in 19 patients. Median number of DLI administered was 2 (range 1-11). Univariate analysis demonstrated 2-year overall survival (OS) for second-HCT was superior when performed for relapse (65%) compared to GF (44%) (p=0.03). For DLI patients, 2-year OS was 49% for GF and 45% for relapse patients (p=0.49). For relapse as an indication, second-HCT demonstrated borderline superiority compared to DLI (p=0.07). Multivariable analysis demonstrated for OS for the entire cohort demonstrated donor mismatch (HR 0.50, 95%CI 0.26-0.94%, p=0.03), KPS at time of intervention (HR 2.10, 95%CI 1.14-3.85%, p=0.02) and time from first-HCT to intervention (HR 0.51, 95%CI 0.28-0.93%, p=0.03) as significant variables. Conclusion: Second-HCT may improve outcomes when performed for relapse post-transplant if patients achieve remission again, while DLI may be reserved for patients with active disease.

PURPOSE Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD). METHODS This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS). RESULTS Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037). CONCLUSION CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.

PURPOSEClonal hematopoiesis (CH) can be transmitted from a donor to a recipient during allogeneic hematopoietic cell transplantation. Exclusion of candidate donors with CH is controversial since its impact on recipient outcomes and graft alloimmune function is uncertain.PATIENTS AND METHODSWe performed targeted error-corrected sequencing on samples from 1,727 donors age 40 years or older and assessed the effect of donor CH on recipient clinical outcomes. We measured long-term engraftment of 102 donor clones and cytokine levels in 256 recipients at 3 and 12 months after transplant.RESULTSCH was present in 22.5% of donors, with DNMT3A (14.6%) and TET2 (5.2%) mutations being most common; 85% of donor clones showed long-term engraftment in recipients after transplantation, including clones with a variant allele fraction < 0.01. DNMT3A-CH with a variant allele fraction ≥ 0.01, but not smaller clones, was associated with improved recipient overall (hazard ratio [HR], 0.79; P = .042) and progression-free survival (HR, 0.72; P = .003) after adjustment for significant clinical variables. In patients who received calcineurin-based graft-versus-host disease prophylaxis, donor DNMT3A-CH was associated with reduced relapse (subdistribution HR, 0.59; P = .014), increased chronic graft-versus-host disease (subdistribution HR, 1.36; P = .042), and higher interleukin-12p70 levels in recipients. No recipient of sole DNMT3A or TET2-CH developed donor cell leukemia (DCL). In seven of eight cases, DCL evolved from donor CH with rare TP53 or splicing factor mutations or from donors carrying germline DDX41 mutations.CONCLUSIONDonor CH is closely associated with clinical outcomes in transplant recipients, with differential impact on graft alloimmune function and potential for leukemic transformation related to mutated gene and somatic clonal abundance. Donor DNMT3A-CH is associated with improved recipient survival because of reduced relapse risk and with an augmented network of inflammatory cytokines in recipients. Risk of DCL in allogeneic hematopoietic cell transplantation is driven by somatic myelodysplastic syndrome–associated mutations or germline predisposition in donors.

International audience; Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.

Background: Patients receiving allogeneic hematopoietic cell transplantation (HCT) have high morbidity and mortality risk, but literature is limited on factors associated with end-of-life (EOL) car...

Infections are still a major reason of morbidity and one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper is presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation of Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing ECIL (European Conference on Infections in Leukemia) and EBMT (European Society of Blood and Marrow Transplantation) guidelines, as well as results of survey performed among all Polish transplant centers, were the background material for working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented.

Key Points The incidence of acute cardiac toxicity remains low and manageable after matched allo-HCT in the era of PTCy prophylaxis.Older age, hypertension, arrhythmia, diabetes, and cardiac comorbidities increase this risk of cardiac toxicity but PTCy did not., Visual Abstract, Graft-versus-host disease (GVHD) is one of the leading causes of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). Posttransplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicity, and few studies have evaluated the cardiac toxicities that arise after PTCy. We completed a retrospective analysis of patients who underwent matched-donor allo-HCT at our institution and who received PTCy- or non-PTCy–based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after allo-HCT. We included 585 patients in our analysis and found that 38 (6.5%) experienced cardiac toxicity after allo-HCT. The toxicities included arrhythmias (n = 21), heart failure (n = 14), pericardial effusion (n = 10), and myocardial infarction or ischemia (n = 7). Patients who received PTCy had a 7.4% incidence of cardiac toxicity, whereas non-PTCy recipients had an incidence of 5.8% (P = .4). We found that age >55 years (P = .02) and a history of hypertension (P = .01), arrhythmia (P = .003), diabetes (P = .04), and cardiac comorbidities (P < .001) were significant predictors of cardiac toxicity, whereas none of the preparative and GVHD prophylaxis regimens were predictive. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity after allo-HCT. We found that a higher score correlated with an incidence of cardiac toxicity. Furthermore, the development of cardiac toxicity was associated with worse 1-year overall survival (OS) and NRM. The use of PTCy was associated with improvements in 1-year OS and NRM rates.

Hematopoietic cell transplantation (HCT) is the curative treatment for many malignant and non-malignant blood disorders and some solid cancers. However, transplant procedures are considered tertiary level care requiring a high degree of technicality and expertise and generating very high costs for hospital structures in developing countries as well as for patients without health insurance. During the 11th annual harmonization workshops of the francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC), a designated working group reviewed the literature in order to elaborate unified guidelines, for developing the transplant activity in emerging countries. Access to infrastructure must comply with international standards and therefore requires a hospital system already in place, capable of accommodating and supporting the HCT activity. In addition, the commitment of the state and the establishment for the financing of the project seems essential.

Introduction The increasing proportion of outpatient allogeneic hematopoietic cell transplants (HCTs) coupled with increased access of once‐daily broad‐spectrum antibiotics and evidence that outpatient antibiotic treatment may be safer and less costly than inpatient treatment, suggest that allogeneic HCT recipients with Gram‐negative rod bacteremia (GNRBs) are increasingly being treated in ambulatory care settings. Methods Using data from the first GNRB event that occurred within the first 100 days posttransplantation among allogeneic HCT recipients transplanted at a single center between 2007 and 2016, we estimated the temporal trends in GNRB incidence and treatment management of GNRBs and identified if patient or infection characteristics impacted observed trends. Results A total of 11% (238/2165) of the observed allogeneic HCT recipients experienced ≥1 GNRB with available resistance data and contributed antibiotic treatment time. Patients, on average, received 55.1% of their antibiotic treatment in an outpatient setting and we observed a significant decline in the proportion of treatment time spent outpatient (crude: −3.3% [95% confidence interval: −5.0, −1.6%]). We observed similar declines in the proportion of treatment time spent outpatient among patients with similar GNRB and pretransplant complexity factors but not among patients with similar posttransplant complications (p value: .165). Conclusion These results suggest that, despite increased availability of outpatient suitable treatment options, allogeneic HCT recipients with GNRBs received less treatment in outpatient settings. However, among patients with similar posttransplant complications, the lack of significant decline suggests that treatment location decisions remained consistent for patients with similar posttransplant complications. These findings suggest the need for additional interventions targeting outpatient antibiotic treatment among allogeneic HCT recipients with GNRBs., Over a 10‐year period, Gram‐negative rod bacteremia (GNRB) incidence and the proportion of GNRBs treatment time spent outpatient declined significantly. However, among patients with similar posttransplant complications, no decline in outpatient treatment was observed. This suggests that the decline in outpatient antibiotic days may be linked to increased frequency of posttransplant complications.

BACKGROUND The cytogenetics of acute myeloid leukemia (AML) increases exponentially with age. Adolescent and young adult (AYA) patients have specific psychosocial and other challenges, influencing their ability to access appropriate treatment. Therefore, in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for AML, inferior outcomes would be observed in AYA patients compared to children. METHODS We defined the age range of AYA patients as 15 to 29 years. Sixty-three patients who underwent allo-HSCT from 1998 to 2020 at Chang Gung Children Hospital were enrolled in this study. Overall survival was the time duration from HSCT to death from any cause. Disease-free survival was the time duration from HSCT to the last follow-up or first event (failure to achieve complete remission, relapse, secondary malignancy, or death from any cause). RESULTS Thirty-seven (59%) patients were

Cord blood (CB) is the stem cell source of choice for approximately 30% of pediatric patients undergoing hematopoietic cell transplantation. Cord blood is readily available and is a particularly appealing stem cell source for patients who lack appropriate HLA-matched related or unrelated donors. Pediatric cord blood transplant (CBT) recipients have low rates of disease relapse in the malignant setting and very low rates of chronic graft-versus-host disease (GVHD). In addition, CB has unique properties that make it the stem cell source of choice for some nonmalignant conditions such as metabolic disorders. This review provides evidence-based and experience-based pediatric-specific guidelines for CBT including considerations for infectious disease management, CB unit selection and infusion, conditioning regimen selection, and GVHD management. In addition, it covers unique bedside considerations for pediatric patients and CB banking. In concert with the other topic specific CB guidelines previously published in this series, it provides a comprehensive overview of the clinical management of pediatric CBT.

The Practice Guidelines Committee of the American Society of Transplantation and Cellular Therapy (ASTCT) partnered with its Transpl. Infect. Dis. Special Interest Group (TID-SIG) to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A new approach was employed with the goal of better serving clinical providers by publishing each standalone topic in the infectious diseases series as a concise format of frequently asked questions (FAQ), tables, and figures. Adult and pediatric infectious diseases and HCT content experts developed and answered FAQs. Topics were finalized with harmonized recommendations that were made by assigning an A through E strength of recommendation paired with a level of supporting evidence graded I through III. The fourth topic in the series focuses on the management and treatment of cytomegalovirus (CMV) resistant and refractory infections. The diagnosis, definitions of resistant and refractory CMV, risk factors, virological genotypes and treatment algorithms are reviewed.

Background and Purpose Currently there are no widely accepted guidelines for chimerism analysis testing in hematopoietic cell transplantation (HCT) patients. The objective of this review is to provide a practical guide to address key aspects of performing and utilizing chimerism testing results. In developing this guide, we conducted a survey of testing practices among laboratories that are accredited for performing engraftment monitoring/chimerism analysis by either the American Society for Histocompatibility & Immunogenetics (ASHI) and/or the European Federation of Immunogenetics (EFI). We interpreted the survey results in the light of pertinent literature as well as the experience in the laboratories of the authors. Recent developments In recent years there has been significant advances in high throughput molecular methods such as next generation sequencing (NGS) as well as growing access to these technologies in histocompatibility and immunogenetics laboratories. These methods have the potential to improve the performance of chimerism testing in terms of sensitivity, availability of informative genetic markers that distinguish donors from recipients as well as cost. Summary The results of the survey revealed a great deal of heterogeneity in chimerism testing practices among participating laboratories. The most consistent response indicated monitoring of engraftment within the first 30 days. These responses are reflective of published literature. Additional clinical indications included early detection of impending relapse as well as identification of cases of HLA-loss relapse.

BACKGROUND AND OBJECTIVE Reception of social support may foster adjustment in dyads facing cancer treatment. Still, understanding of the effects of received support in everyday life of patient-caregiver dyads remains limited. This study investigated whether the positive effect of daily received social support depends on daily stress levels and whether the effect differs by perspective (recipient vs. provider) in dyads undergoing hematopoietic cell transplantation (HCT). DESIGN AND METHODS The sample comprised 200 patient-caregiver dyads after HCT. The participants completed measures of daily stress levels, received and provided social support as well as affect for 28 consecutive days. RESULTS Regardless of daily stress levels, the caregivers reported better affect on days when they noticed more received support (recipient perspective), whereas the patients reported worse affect on days when they noticed more received support (recipient perspective) and/or when their caregivers reported higher provided support (provider perspective). CONCLUSION The effects of daily received support were not related to the levels of daily stress in patient-caregiver dyads after HCT. Also, the effects varied by role (benefits in the caregivers vs. harm in the patients) and perspective (similarities in the patients vs. differences in the caregivers).

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for myelodysplastic syndromes (MDS), although it is infrequently offered to older patients. The relative benefits of HCT over non-HCT therapy in older patients with higher-risk MDS have not been defined. METHODS We conducted a multicenter biologic assignment trial comparing reduced-intensity HCT to hypomethylating therapy or best supportive care in subjects 50-75 years of age with intermediate-2 or high-risk de novo MDS. The primary outcome was overall survival probability at 3 years. Between January 2014 and November 2018, we enrolled 384 subjects at 34 centers. Subjects were assigned to the Donor or No-Donor arms according to the availability of a matched donor within 90 days of study registration. RESULTS The median follow-up time for surviving subjects was 34.2 months (range: 2.3-38 months) in the Donor arm and 26.9 months (range: 2.4-37.2 months) in the No-Donor arm. In an intention-to-treat analysis, the adjusted overall survival rate at 3 years in the Donor arm was 47.9% (95% CI, 41.3 to 54.1) compared with 26.6% (95% CI, 18.4 to 35.6) in the No-Donor arm ( P = .0001) with an absolute difference of 21.3% (95% CI, 10.2 to 31.8). Leukemia-free survival at 3 years was greater in the Donor arm (35.8%; 95% CI, 29.8 to 41.8) compared with the No-Donor arm (20.6%; 95% CI, 13.3 to 29.1; P = .003). The survival benefit was seen across all subgroups examined. CONCLUSION We observed a significant survival advantage in older subjects with higher-risk MDS who have a matched donor identified and underwent reduced-intensity HCT, when compared with those without a donor. HCT should be included as an integral part of MDS management plans in fit older adults with higher-risk MDS.

We evaluated the impact on survival of antithymocyte globulin conditioning (TLI-ATG) with radiation (RT) boost to high risk or residual disease before allogeneic hematopoietic cell transplant (allo-HCT) for adults with lymphoma (excluding mycosis fungoides and low-grade NHL other than SLL/CLL). Of 251 evaluable patients, 36 received an RT boost within 3 months of allo-HCT at our institution from 2001 to 2016. At the time of TLI-ATG, patients who received boost vs no boost had a lower rate of CR (11% vs 47%, p = 0.0003), higher rates of bulky disease (22% vs 4%, p < 0.0001), extranodal disease (39% vs 5%, p < 0.0001), and positive PET (75% vs 28%, p < 0.00001). In the boost group, the median (range) largest axial lesion diameter was 5.2 cm (1.8-22.3). Median follow-up was 50.2 months (range: 1-196). There was no significant difference in OS, time to recurrence, or time to graft failure with vs without boost. A trend toward higher percent donor CD3+ chimerism was seen with vs without boost (p = 0.0819). The worst boost-related toxicity was grade 2 dermatitis. RT boost may help successfully mitigate the risk of high risk or clinically evident residual disease in adults with lymphoma undergoing allo-HCT.

Hematopoietic cell transplant (HCT) is an increasingly common and curative treatment strategy to improve survival among individuals with malignant and nonmalignant diseases, with over one million HCTs having been performed worldwide. Neurocognitive dysfunction is a common and untoward consequence of HCT for many recipients, although few studies have examined the profile of neurocognitive impairments in HCT or their association with clinical features, such as frailty, or the incidence of pre-HCT neurocognitive impairments across all ages, which may influence post-HCT neurocognitive impairments. We examined the pattern and correlates of pre-transplant neurocognitive dysfunction in a prospective sample of adults undergoing HCT. Neurocognition was assessed using the Montreal Cognitive Assessment Battery. Frailty was assessed using the Short Physical Performance Battery. Linear regression analysis was used to examine the associations between neurocognitive performance and frailty. Neurocognitive screening profiles were also examined by partitioning MoCA into domain scores, including Executive Function and Memory. We also examined the associations between neurocognition, frailty, and clinical outcomes, including length of transplant hospitalization and survival. One hundred and ten adults were evaluated across a wide age range (range: 19-75; mean age = 54.7 [SD = 14.1]). Neurocognitive performance tended to fall below published normative levels (mean MoCA = 25.5 [SD = 4.1]), with 17% of participants demonstrating impaired performance compared with medical normative data (MoCA ≤ 22) and 34% exhibiting impaired performance relative to healthy samples (MoCA ≤ 25). Mild impairments (MoCA ≤ 25) were common across age ranges, including middle-aged patients (23% for age < 50; 35% for age 50-60, 41% for age ≥ 60), particularly for items assessing Executive Function. Greater levels of frailty associated with lower neurocognitive screening scores (r = -0.29, P < 0.01) and Executive Functioning (r = -0.24, P < 0.01), whereas greater age was associated with poorer Memory performance only (r = -0.33, P < 0.01). Greater levels of frailty prior to transplant associated with longer length of stay (β = 0.10, P = 0.046), but were not associated with survival. Neurocognitive impairments are common among adults undergoing HCT and the pattern of performance varies by age. Pre-transplant frailty is associated with neurocognitive functioning and may portend worse post-transplant early clinical outcomes.

Allogeneic hematopoietic cell transplantation (alloHCT) survivors have been recently recognized as patients at increased cardiovascular risk. We hypothesized that vascular function remains impaired in alloHCT survivors free of graft-versus-host-disease or relapse. We enrolled consecutive adult alloHCT survivors and non-HCT control individuals (January 2019-March 2020), matched for traditional cardiovascular risk factors. Microvascular dysfunction was dynamically assessed in real time by Laser Speckle Contrast Analysis (LASCA). Carotid-femoral pulse-wave velocity (PWV) and carotid intima media thickness (IMT) were assessed as surrogate markers of cardiovascular disease. We studied 75 patients after a median of 3.2 (range 2.1-4.9) years from alloHCT, who had suffered from grade 2 to 3 acute (20%) and/or moderate/severe chronic GVHD (42%), and 75 controls. Although traditional cardiovascular risk factors and surrogate markers of cardiovascular disease did not differ between groups, alloHCT survivors showed significantly impaired microvascular function (baseline and peak flux, time to peak, base to peak and base to occlusion change). LASCA indices were also independently associated with alloHCT. Our study shows for the first-time impaired microcirculation dynamics in alloHCT survivors, independently of cardiovascular risk factors. Additional studies are needed to address the role of novel markers in cardiovascular risk prediction, along with effects of disease type, phase, and pre-transplant treatments.

Autologous hematopoietic cell transplantation (HCT) is an effective therapy for patients with relapsed acute promyelocytic leukemia (APL). However, it remains unclear whether this procedure is equally effective for certain groups of patients. To address this question, we analyzed 296 patients with APL who had undergone autologous HCT during second or subsequent complete remission (CR2+) between 2006 and 2019. Among them, 24 patients were ≥65 years old, and 17 underwent autologous HCT during third or subsequent CR. Of the 286 patients whose measurable residual disease (MRD) data were available, 21 showed detectable MRD. The 5-year probabilities of relapse-free survival (RFS), overall survival, relapse, and nonrelapse mortality for the entire cohort were 85%, 88%, 9%, and 6%, respectively. The multivariate analysis revealed that the duration of first CR (

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive hematological malignancy; however, some patients achieve durable remission with allogeneic hematopoietic cell transplantation (allo-HCT). We report on all 17 patients with BPDCN who underwent allo-HCT at our center between 2000 and 2020. The median age was 39 (18-67) years. All (n = 16, 94%), except one patient, had systemic disease involving bone marrow and/or other organs. Ten patients (59%) were in first complete remission (CR1) at allo-HCT. The donor source was matched related or unrelated in ten (59%) and alternate donor in seven (41%) patients. Five (31%) patients developed acute graft-versus-host disease (GVHD), all grade I-II. The cumulative incidence (CI) of chronic GVHD at five-year was 34%. The CI of non-relapse mortality at one-year was 29%. Progression-free survival (PFS) rates at two-year and five-year were 49% (95% CI = 22-71%) and 39% (95% CI = 14-64%), respectively. The two-year and five-year overall survival (OS) rates were 65% (95% CI = 38-82%) and 40% (95% CI = 12-68%), respectively. The five-year rate for both PFS and OS was 80% in CR1 patients versus 0% in patients not in CR1. In conclusion, allo-HCT provides long-lasting remissions in BPDCN patients, particularly when performed in CR1.

Isolated extramedullary relapse (EMR) without bone marrow relapse (BMR) after allogeneic hematopoietic cell transplantation (allo-HCT) is a rare condition in patients with acute lymphoblastic leukemia (ALL), and the role of immunotherapeutic agents for these patients remains unclear. We analyzed treatment outcomes of blinatumomab or inotuzumab ozogamicin (INO) as first- or second-line salvage therapy in nine patients with Philadelphia chromosome-negative B-cell precursor ALL presenting with isolated EMR after previous allo-HCT. In seven patients receiving blinatumomab as first-line salvage therapy, 4 (57.1%) achieved complete remission (CR). Among the three patients without remission after blinatumomab, two switched to INO and subsequently showed responses {one CR and one partial response [PR]}, and one switched to multiagent chemotherapy that led to CR. In the two patients receiving first-line salvage therapy with INO, one showed PR and the other achieved CR. Overall, 6 (66.7%) of nine patients achieved CR, and five of them proceeded to allo-HCT in CR. The median overall survival after relapse was 27.8 months. In conclusion, both blinatumomab and INO showed good response rates and a safe bridging role to second allo-HCT in patients with isolated EMR. However, clinical differences between isolated EMR and EMR with BMR remain to be elucidated.

Engraftment syndrome (ES) after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) encompasses a continuum of periengraftment complications characterized by noninfectious fever, rash, diarrhea, and capillary leak features.We analyzed the ES outcomes in 257 consecutive patients MM patients who underwent AHCT at our institution from 12/2017 to 11/2019 with budesonide prophylaxis (3 mg PO daily at day +5 post-AHCT till the time of discharge) (N = 109) and no prophylaxis (N = 148).The rates of ES were significantly higher in the no prophylaxis group versus prophylaxis group [69 (46%) vs. 23 (21%); P.001]. There was no significant difference in length of stay (LOS) [mean 15 (±3.2) vs. 16 (±2.8); P = .27] and 30-day readmission [9 (6%) vs. 8 (7%); P = .81] between the no prophylaxis and prophylaxis groups, respectively. On adjusted analysis, budesonide prophylaxis was associated with a significantly lower risk of developing ES [odds ratio (OR) 0.29 (95% confidence interval [CI], 0.16-0.51); P.0001]. There was no difference in the 30-day readmission rates [OR 1.12 (95% CI, 0.41-3.03); P = .81], but a trend for shorter LOS in the prophylaxis group [7.3% reduction in LOS (95% CI, -14.4% to 0%); P = .06].Budesonide prophylaxis significantly reduces the risk of ES in MM patients undergoing AHCT. These promising results suggest the need for a randomized study investigate the role of budesonide for ES prophylaxis.

Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II-IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Stem cell source or HLA disparity may exert a significant impact on the overall survival (OS) after the development of aGVHD. In order to clarify this point, we performed a retrospective analysis using a database of the Japan Society for HCT. We analyzed the clinical outcomes of 10,035 patients who developed grade II-IV aGVHD. The median age of the patients was 48 years. The probability of 2-year OS after the onset of grade II-IV aGVHD in the study cohort was 54.1%. The multivariate analysis showed that the HLA ≥2-loci mismatched related donor and HLA 1-locus mismatched unrelated donor were significantly associated with an inferior OS after grade II-IV aGVHD. In a subgroup analysis, peripheral blood stem cells and HLA disparity were associated with an inferior OS in patients who received related or unrelated HCT. Thus, the clinical outcome after grade II-IV aGVHD significantly varied as per the combination of the presence of HLA disparity and stem cell source. Further research using other databases is necessary to confirm our findings.

Introduction To help monitor and manage complications, monitor disease progression, and help lower morbidity and mortality rates in Hematopoietic cell transplant (HCT) patients, the use of artificial intelligence technology can prove to be an efficient tool. Aim We propose a futuristic vision of an artificial intelligence model which could help in early detection of MSK related complications, improve communication between HCT healthcare professional team, improve diagnostics via machine learning (ML), help monitor symptom/ disease progression remotely, and help integrate services for a more patient-friendly service delivery, i.e., drug prescription, exercise prescription, appointment tracking, referral pathways. Materials and methods The proposed model is a three-phase integrated program where musculoskeletal physical examination is combined with wearable textiles interface platform and machine learning algorithms, thereby providing live and remote feedback of changes as they happen in at the musculoskeletal and vital signs level. Result With the help of machine learning technology, various algorithms can be created to help improve remote and live diagnostic accuracy of post-HCT musculoskeletal manifestations. Subtle changes over the course of time in various patient groups can be detected at the skin, fascia, muscle, bone level; thereby helping in better understanding of the disease and its management.

To characterize the issues regarding work and employment specific to allogeneic hematopoietic cell transplantation (allo-HCT) survivors, we conducted a nationwide cross-sectional questionnaire survey. We targeted allo-HCT survivors employed at diagnosis, aged 20–64 at survey, and survived ≥2 years without relapse. The questionnaire included the timing of and reasons for resignation (termination of employment contract), and patient-related, HCT-related, work-related, and HCT center-related factors. A total of 1048 eligible participants were included in the analysis (response rate, 60%). The median time after allo-HCT was 5 years (range, 2–30) at the time of survey. After diagnosis, 41% of participants resigned from work throughout the course of treatment. The most frequent timing of the first resignation was “after discharge post-HCT” (46%), followed by “from diagnosis to initial treatment” (27%). Factors significantly associated with resignation included female gender, older age, and part-time employment. Favorable factors included the presence of occupational health staff at the workplace, employment of ≥10 years, and self-employed/freelance. After resignation, the overall incidence of return to work with some accommodations was 76% at 5 years after HCT, but it was 52% without any accommodation. Overall, the rate of resignation was 41%, and the most frequent timing of resignation was after discharge post-HCT, accounting for approximately half of the resignations (46%). Workplace accommodations increased the rate of return to work from 52% to 76%. Early detection of employment-related concerns and support throughout the treatment process are necessary for patients receiving allo-HCT.

This study characterized the outcomes of patients who underwent hematopoietic cell transplantation (HCT) for transformed follicular lymphoma (tFL), and clarified the association of low-dose anti-thymocyte globulin use with outcomes after allogeneic HCT. The retrospective study cohort included 74 consecutive patients who underwent autologous (n = 23) or allogeneic (n = 51) HCT at our center from 2000 to 2017. Compared with the allogeneic HCT group, the autologous HCT group underwent fewer systemic regimens before HCT (median 2 vs. 5, p < 0.001) and were more likely to have chemosensitive disease at HCT (100% vs. 82%, p = 0.05), while age, sex and HCT-specific comorbidity index were similar between the two groups. With a median follow-up of 5.8 years among survivors, the 5-year probability of progression-free survival was 64% after autologous HCT and 55% after allogeneic HCT (p = 0.21). The 5-year cumulative incidence of non-relapse mortality was 0% after autologous HCT and 9.5% after allogeneic HCT (p = 0.062). The 5-year cumulative incidence of disease progression was similar between autologous and allogeneic HCT (36% vs. 36%, respectively, p = 0.88). In the allogeneic HCT group, the use of low-dose anti-thymocyte globulin was associated with a lower incidence of severe acute GVHD but not with an increased risk of mortality or disease progression. More than half of patients with early phase chemosensitive tFL and approximately half of those with advanced-phase tFL achieved long-term progression-free survival with autologous and allogeneic HCT, respectively. Disease progression was the major cause of treatment failure after both types of HCT. Further strategies are needed to reduce the risk of disease progression.

Introduction The use of checkpoint blockade therapy (CBT) has shown impressive results for the treatment of relapsed/refractory Hodgkin lymphoma (cHL). The impact of CBT depends on the reversal of an exhausted T-cell immune phenotype and a consequential increase in the immunological, anti-tumor effect derived from a patient's adaptive immunity. As most patients with classical Hodgkin lymphoma will relapse during or after this treatment, clinicians often provide consolidation with allogeneic hematopoietic cell transplantation (alloHCT) is fit patients. However, the mechanisms responsible for CBT efficacy can also be those that increase the risk of immunological complications after alloHCT. Areas covered We carried out in-depth research on current medical literature to report and discuss the mechanism of action of CBT within a cHL setting; clinical results of CBT in cHL setting pre-alloHCT and post-alloHCT; interactions between CBT and alloHCT; and further clinical considerations. Expert opinion Checkpoint blockade therapy is an effective strategy for relapsed/refractory cHL. Its use is associated with higher immunological toxicities when administered before or after alloHCT. Whenever alloHCT is planned, clinicians should follow international recommendations such as using post-transplant cyclophosphamide GVHD prophylaxis.

Patients undergoing hematopoietic cell transplantation (HCT) and their caregivers can experience psychosocial complications pre-, during, and post-transplant. To meet the needs of the most patients and caregivers, a class was developed to prepare patients and caregivers to prevent and manage common psychosocial challenges. We evaluated the feasibility and acceptability of the class over a 5-month pilot period. Attendance in this class became part of standard pre-transplant care. Attendees were invited to complete a questionnaire (Likert-scale and open-ended questions) to evaluate the feasibility and acceptability of this class. Data were collected over a 5-month period. Descriptive analysis was completed. Patients (n = 41) and caregivers (n = 40) were satisfied to very satisfied with the class. Patients (80%) and caregivers (65%) reported that the class met their expectations, with several describing it as worthwhile and informative. Information relating to finances and benefits were considered most helpful, followed by emotional support resources. Patients (73%) and caregivers (93%) reported that they would recommend the class to others. This education class should be provided as early as possible to ensure that psychosocial needs are addressed. Future research initiatives include further assessing the perspectives of patients, clinicians, and other stakeholders; evaluating delivery methods; and collaborating with other centers.

To evaluate whether outcomes following allogeneic hematopoietic cell transplantation differ according to disease type, a three-way comparison for patients with de novo acute myeloid leukemia (AML) (n = 3318), AML evolving from myelodysplastic syndromes (MDS) (n = 208), and MDS with excess blasts (MDS-EB) (n = 994) was performed. The 5-year probabilities of overall survival (OS) for de novo AML, AML evolving from MDS, and MDS-EB were 60%, 42%, and 41% (p < 0.001), respectively. Multivariate analysis revealed that, compared to de novo AML, AML evolving from MDS was associated with a higher risk of NRM (p = 0.030) and MDS-EB with a higher risk of relapse (p < 0.001), both leading to lower OS (p = 0.010 and p < 0.001, respectively). These findings demonstrate inter-disease differences in post-transplant outcomes and highlight the needs to reduce NRM for AML evolving from MDS and to reduce relapse for MDS-EB.

With the recent development of transplant-specific composite endpoints for evaluation of allogeneic hematopoietic cell transplantation (alloHCT) outcomes, the use of these novel endpoints is growing rapidly. Combining multiple endpoints into a single endpoint, these composite endpoints appear simple and can be used as a summary measure for overall effectiveness of an intervention. However, all component endpoints may not have equal clinical significance, and an intervention may not work proportionally in the same direction for all components of a composite endpoint. This may complicate the interpretation of results, particularly if there are opposing effects of differing component endpoints. We assess the benefits and limitations of various composite endpoints used in alloHCT studies recently and propose guidelines for their use and interpretation. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Relapse after allogeneic hematopoietic cell transplantation (HCT) leads to poor survival in patients with acute myeloid leukemia (AML). A second HCT (HCT2) may achieve durable remission. To determine the outcomes of patients who received an HCT2 for relapsed AML and to evaluate the predictors of overall survival (OS) and progression-free survival (PFS). We retrospectively reviewed medical records of adult patients who underwent an HCT2 for relapsed AML at our institution during 2000 to 2019. Ninety-one patients were identified with a median age of 44 years (range 18-73) at HCT2. Donor types were HLA-identical sibling (n = 37 [41%]), HLA-matched–unrelated (n = 34 [37%]), haploidentical (n = 19 [21%]), and cord blood (n=1 [1%]). Donors were different at HCT2 in 53% of patients. The majority of patients received reduced intensity conditioning (n = 71 [78%]) and were in remission (n = 56 [61%]) at HCT2. The median remission duration after HCT1 was 8.4 months (range 1-70) and the median time between transplants was 14 months (range 3-73). The median follow-up of surviving patients after HCT2 was 66 months (range 2-171), with 32% alive at time of analysis. The most common cause of death was disease recurrence (n = 45 [73%]). At 2 years, the rates of OS, PFS, progression, and nonrelapse mortality were 36%, 27%, 42%, and 18%, respectively. The development of chronic graft-versus-host disease (GVHD) after first HCT and HCT comorbidity index (HCT-CI) ≥2 at HCT2 were associated with inferior PFS and OS after HCT2. A second HCT is feasible in selected patients with AML who have relapsed after HCT1. Long-term survival benefit is possible in patients without chronic GVHD after HCT1 and HCT-CI

Despite multiple advances in the treatment landscape of chronic lymphocytic leukemia (CLL) during recent years, cellular therapies, such as allogeneic hematopoietic cell transplantation and chimeric antigen-engineered T cells, represent valuable therapeutic options for patients with multiply relapsed or poor-risk disease. This brief overview will summarize current results of cellular therapies in CLL including Richter transformation, suggest an indication algorithm and strategies for performing cellular therapies in these conditions, and discuss the impact of COVID-19 (coronavirus disease 2019) on allogeneic hematopoietic cell transplantation and chimeric antigen-engineered T cells in CLL.

Background. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curable treatment modality for hematologic disorders. Transplant-related mortality remains high despite prominent scientific and technologic improvements. In consideration with the potential impact of patient- and disease-related factors on transplant outcome, this retrospective study was performed to investigate the predictive role of pretransplant HCT-composite risk (HCT-CR) score in alloHCT recipients. Methods. A total of 313 patients with acute leukemia (male/female: 192/121; median age, 36 [18-71] years) were included in this study. The study cohort was divided into 2 subgroups based on pretransplant HCT-CR categories. The HCT-CRlo group included low-risk patients, and the HCT-CRint-hi group consisted of intermediate-, high-, and very high-risk patients. Results. In the whole cohort, overall survival (OS) and 5-year OS were found to be 32.2% and 45.1%, respectively. Probability of OS was significantly better in the HCT-CRlo group compared with the HCT-CRint-hi group (P < .001). Leukemia-free survival (LFS) and 3-year LFS were 59.5% and 65.1%, respectively. Probability of LFS was better in the HCT-CRlo group compared with the HCT-CRint-hi group (P = .001). Nonrelapse mortality (NRM) and 3-year NRM were estimated to be 38.1% and 27.5%, respectively. Probability of NRM was significantly higher in the HCT-CRint-higroup compared with the HCT-CRlo group (P = .012). In multivariate analysis, HCT-CR was shown to have significant prognostic impact in acute lymphoblastic leukemia patients (P = .023; hazard ratio, 2.613; 95% CI, 1.142-5.982). Conclusion. Pretransplant evaluation of patient- and disease-related factors is essential for the accurate prediction of posttransplant survival. Further efforts to evolve current criteria for pretransplant risk assessment would eventuate in better transplant outcomes.

History of venous thromboembolism (VTE) is prevalent among patients undergoing hematopoietic cell transplantation (HCT). Management of anticoagulation is particularly challenging as most patients will have chemotherapy-induced thrombocytopenia while awaiting engraftment post-HCT. We conducted a retrospective study of autologous and allogeneic HCT recipients with prior VTE from 2006-2015 to 1) compare anticoagulant strategies on short-term VTE recurrence and bleeding and 2) assess predictors for VTE recurrence beyond 30 days. After inverse probability of weighting, patients with VTE were allocated to two cohorts based on anticoagulant strategy at thrombocytopenia onset to assess primary outcomes of VTE recurrence and bleeding within 30 days post-HCT. Multivariable logistic regression model was designed to assess the association of 100-day VTE recurrence by the HIGH-2-LOW VTE risk assessment score and whether patients resumed anticoagulation at platelet recovery. Thirteen percent of recipients had VTE prior to HCT; of those meeting inclusion criteria, 227 continued anticoagulation and 113 temporarily discontinued. Anticoagulant strategy was not significantly associated with decreased risk of VTE recurrence within 30 days (3% vs 4%, p=0.61); however, risk of overall bleeding was non-significantly higher in those who continued vs. discontinued anticoagulation (41% vs 31%, p=0.08). Among 250 allogeneic HCT patients, every 1-point increase of HIGH-2-LOW score was significantly associated with VTE recurrence at 100 days (OR 1.57 [95% CI 1.10-2.23]), while anticoagulation resumption upon platelet engraftment was associated with lower recurrent risk (OR 0.48 [0.20-1.14]). Temporarily withholding anticoagulation during thrombocytopenia may optimize risk-benefit tradeoffs, though additional strategies are essential to prevent VTE recurrence after hematopoietic recovery. This article is protected by copyright. All rights reserved.