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We analyzed outcomes of 126 patients with hematologic malignancies, who relapsed after first allogeneic hematopoietic cell transplantation (HCT) and received subsequent allografts. In 17 cases, the original donors were utilized, while in 109 cases different donors were identified. The 2-year overall survival (OS), relapse, and non-relapse mortality (NRM) rates were 33%, 42%, and 33%, respectively. Patients with early relapse after first allogeneic HCT (within 100 days vs. 100 days to 12 months vs. >12 months) had higher relapse rates (50% vs. 47% vs. 34%, respectively; p = .01) and worse OS (15% vs. 25% vs. 45%, respectively, p = .005) at 2 years after second allogeneic HCT. In conclusion, second allogeneic HCT should be considered in patients who relapse after first allografts, especially in those who relapse after more than a year. Utilizing a different donor for the second allotransplant including umbilical cord blood or HLA-haploidentical, related donors did not adversely impact outcomes.

Graft versus host disease (GVHD) is a common complication of allogeneic hematopoietic cell transplantion (HCT) and a major cause of posttransplant morbidity and mortality. Despite recent advancements in our knowledge regarding pathophysiology of GVHD, success in treatment has been limited. Mesenchymal stem cells (MSC) have immunomodulatory and antiinflammatory properties that can be exploited for the prevention and treatment of GVHD, with established preliminary results in early-phase clinical trials. In this chapter, we briefly review HCT and GVHD, and evaluate the evidence for MSC therapy in GVHD.

Patients undergoing hematopoietic cell transplantation (HCT) experience decline in their physical activity during their transplant admission. There is limited experience with prospective monitoring of transplant recipients. We therefore measured physical activity and sleep patterns of subjects undergoing autologous and allogeneic HCT. Eighty-three patients were consented for this study. Sixty-three patients competed the study and had their physical activity prospectively assessed using the fitness-tracking device Fitbit HR. Outcomes included adherence, physical activity, readmission, hematopoietic engraftment, and 100-day survival. Sixty percent of patients (n = 37) underwent autologous HCT, and 40% (n = 26) underwent allogenic HCT. Both groups had a comparable number of steps at admission to the hospital. The number of daily steps during the study period was lower in the allogeneic group (2159 versus 3008, P = .07), as was the minimum number of steps recorded over the transplant admission (allogeneic HCT = 395 versus autologous HCT = 848, P = .01). Patients undergoing allogeneic HCT were less active on the day before discharge (1956 steps versus 3183 steps, P = .08). In multivariate analysis, physical activity was not associated with HCT-related outcomes. Patients undergoing HCT experience significant decline in their physical activity during their transplant admission that does not recover by the time of discharge. This effect can be objectively measured using fitness tracking devices.

2538 Background: Allogeneic HCT is a potentially curative therapy for many patients with AML that relies on a graft-versus-leukemia (GvL) effect. Patients who relapse after allogeneic HCT have a poor prognosis and few treatment options. Donor lymphocyte infusion (DLI) can achieve a GvL effect in some patients, however, efficacy is frequently associated with the development graft-versus-host disease (GVHD). There is a substantial need for treatment approaches that enhance the benefit of GVL while decoupling toxicities associated with GVHD. Methods: We report ongoing results from a first-in-human study (NCT04284228) of a non-genetically engineered, donor-derived adoptive cellular therapy product, NEXI-001, which contains multiple populations of CD8+ T cells that recognize different HLA 02.01-restricted peptides from the WT1, PRAME, and Cyclin A1 antigens. NEXI-001 contains T cell memory subtypes that combine anti-tumor potency with long-term persistence. Results: At the time of this analysis, 7 patients with relapsed AML after allogeneic HCT were enrolled. Five Patients were treated with single infusions of NEXI-001 at three different dose levels: 50, 100 and 200 million. Currently, the median follow-up is 5 months. Significantly, GVHD, cytokine release syndrome, neurotoxicity, or NEXI-001-related adverse events were not observed. NEXI-001 treatment resulted in reductions in red blood cell and platelet transfusions and increased donor chimerism. Decreases in myeloblasts in bone marrow and peripheral blood and reduction in the size of an extramedullary myeloid sarcoma were suggestive of an anti-leukemia effect (Table). Correlative studies indicate that NEXI-001 CD8+ cells undergo a rapid proliferation after infusion and are also associated with a robust hostlymphocyte recovery that occurs as quickly Day 3 after infusion. NEXI-001 infused CD8+T cells are detectable by multimer staining in peripheral blood of patients and proliferate over time. TCR sequencing analyses determined that infused NEXI-001 cells contain T cell clones that were undetectable in the peripheral blood of patients at baseline but were detected in blood and bone marrow and persist over time. Conclusions: NEXI-001 has the potential to enhance GvL effect without the associated toxicities of GVHD, cytokine release syndrome, and neurotoxicity. Due to these encouraging results, the trial will proceed with an evaluation of repeated NEXI-001 dosing Clinical trial information: NCT04284228. [Table: see text]

Hematopoietic cell transplantation (HCT) is a treatment for hematologic malignancies and disorders. Patients who receive HCT can face long-term physical and psychosocial effects. Survivorship care guides (care guides), which describe screening and preventive care practices were mailed to allogenic HCT recipients at clinically important timepoints (6, 12, and 24 months after HCT). The primary objective of this study was to evaluate how patients perceived and used the care guides. A cross-sectional, time-series survey was sent to all National Marrow Donor Program/Be The Match allogeneic HCT recipients from September 2012 to November 2016 after the care guides were sent; patients or caregivers could respond. Respondents who returned all 3 surveys were included (554 patients; 65 caregivers), for an overall response rate of 13% (maintenance rate of 45%). The majority of patients and caregivers strongly agreed or agreed that the care guides helped them understand that post-HCT care is important to staying healthy and that they were more familiar with recommended tests at check-up appointments. Most patients who did not share the care guides with their doctors at any of the timepoints believed their doctor knew which tests were needed. Results from this study can help inform and guide development of future tools and evaluations of educational resources for patients after HCT. Tools and educational resources, such as survivorship care guides, have the potential to help empower patients to be more knowledgeable and to understand and advocate for their survivorship care needs.

The efficacy of primary prophylaxis with atovaquone in preventing Toxoplasma reactivation and disease in hematopoietic cell transplant (HCT) recipients is unknown. We describe 2 cases of atovaquone prophylaxis failure in pre-HCT Toxoplasma-seropositive (pre-HCTSP) recipients who underwent allogeneic HCT (allo-HCT) and review the literature on atovaquone prophylaxis in HCT recipients.

Machine learning techniques are widely used nowadays in the healthcare domain for the diagnosis, prognosis, and treatment of diseases. These techniques have applications in the field of hematopoietic cell transplantation (HCT), which is a potentially curative therapy for hematological malignancies. Herein, a systematic review of the application of machine learning (ML) techniques in the HCT setting was conducted. We examined the type of data streams included, specific ML techniques used, and type of clinical outcomes measured. A systematic review of English articles using PubMed, Scopus, Web of Science, and IEEE Xplore databases was performed. Search terms included “hematopoietic cell transplantation (HCT),” “autologous HCT,” “allogeneic HCT,” “machine learning,” and “artificial intelligence.” Only full-text studies reported between January 2015 and July 2020 were included. Data were extracted by two authors using predefined data fields. Following PRISMA guidelines, a total of 242 studies were identified, of which 27 studies met the inclusion criteria. These studies were sub-categorized into three broad topics and the type of ML techniques used included ensemble learning (63%), regression (44%), Bayesian learning (30%), and support vector machine (30%). The majority of studies examined models to predict HCT outcomes (e.g., survival, relapse, graft-versus-host disease). Clinical and genetic data were the most commonly used predictors in the modeling process. Overall, this review provided a systematic review of ML techniques applied in the context of HCT. The evidence is not sufficiently robust to determine the optimal ML technique to use in the HCT setting and/or what minimal data variables are required.

Chronic Myelomonocytic Leukemias are frequently diagnosed in older adults. Their prognosis is heterogeneous, but several prognostic factors can identify patients with an expected survival of a few years only, including among younger patients eligible for allogeneic stem cell transplantation. Based on the retrospective data available, we discuss how to identify CMML patients for whom curative therapy must be envisaged. We emphasize that, although transplantation remains the only path to cure in CMML, it can be envisaged in only a minority of patients. Despite increased donor availability, its potential remains limited by significant rates of mortality caused both by the procedure and by post-transplantation relapses. We review the options available to bridge patients to transplant, the management of transplantation itself (choice of donor, graft source and condition regimen), and finally the potential for post-transplantation interventions. Our review underscores the need for further prospective studies of allogeneic stem cell transplantation in CMML.

Background Advance directives (AD) offer the opportunity for goal-concordant care at the end of life (EOL). However, fewer than half of HCT recipients have a documented AD. We hypothesized that the use of a novel AD-the Stanford What Matters Most Letter (Letter AD)-developed to assess patients' values, goals, and EOL wishes would result in a greater proportion of AD completion among HCT recipients. We therefore conducted a prospective, randomized, controlled study of the traditional California AD vs. the Letter AD in adult allogeneic HCT recipients. Methods Patients >= 18 years old undergoing first allogeneic HCT at Stanford University were eligible. Prior to HCT conditioning, enrolled patients were randomly assigned to complete either the traditional California AD or the Letter AD, and all patients received a sociodemographic survey and a survey evaluating their opinions regarding the AD form they received. Patients were asked to return all research forms at the time of their transplant admission; a research assistant placed a reminder call to each patient prior to scheduled transplant. The primary endpoint was AD completion; secondary endpoints included EOL wishes as documented on the AD and patient preferences and opinions regarding the AD version they received. Results Between March 2017 and August 2018, 212 patients were eligible, of whom 126 (59.4%) were enrolled and randomized. Among the 84 who declined, the primary reason was already having an AD (N=34). The median age was 57 years (IQR 45-64); 54.8% were male; 58.7% were non-Hispanic White; and 72.3% had AML/MDS. There were no statistically significant differences in baseline socio-demographics between study arms. The overall AD completion rate was 71.6% and did not differ between the Traditional and Letter AD study arms (70.3% vs 72.6%, P=0.78). Preferences for EOL among responders are described in Table 1. The Letter AD uncovered that 66.7%, 42.2%, and 46.7% of patients actively wished to die gently/naturally, at home, and/or with hospice, respectively, whereas the traditional AD found that 62.2% wished to not prolong life if recovery was unlikely. Figure 1 portrays participant responses to the AD opinion survey; non-significant trends suggested that patients found the Letter AD favorable in terms of identifying what matters most to them, describing medical preferences to family, and stimulating thinking about the topic. Conclusion Completion rates of AD amongst allogeneic HCT recipients on this study were high and did not differ based upon AD version. Most patients wish to die naturally/do not wish to prolong care at EOL. Non-significant trends favored the Letter AD over the Traditional AD across several domains of patient preference.

Allogeneic HCT practice patterns for PID changed between 1974–2016. Three-year survival improved to >70% for SCID and non-SCID patients after 1999, and further increased to 94% for SCID patients transplanted 2010–2016 following newborn screening diagnosis.

Hematopoietic cell transplantation (HCT) is an established procedure for acquired and congenital disorders of the hematopoietic system. In 2016, there was a tendency for continued activity in this field with 43,636 HCT in 39,313 patients [16,507 allogeneic (42%), 22,806 autologous (58%)] reported by 679 centers in 49 countries in 2016. The main indications were myeloid malignancies 9547 (24%; 96% allogeneic), lymphoid malignancies 25,618 (65%; 20% allogeneic), solid tumors 1516 (4%; 2% allogeneic), and non-malignant disorders 2459 (6%; 85% allogeneic). There was a remarkable leveling off in the use of unrelated donor HCT being replaced by haploidentical HCT. Continued growth in allogeneic HCT for marrow failure, AML, and MPN was seen, whereas MDS appears stable. Allogeneic HCT for lymphoid malignancies vary in trend with increases for NHL and decreases for Hodgkin lymphoma and myeloma. Trends in CLL are not clear, with recent increases after a decrease in activity. In autologous HCT, the use in myeloma continues to expand but is stable in Hodgkin lymphoma. There is a notable increase in autologous HCT for autoimmune disease. These data reflect the most recent advances in the field, in which some trends and changes are likely to be related to development of non-transplant technologies.

Background Hematopoietic cell transplantation (HCT) is an intensive therapy, resulting in prolonged absence from work, with potential for unemployment, extended long-term disability, and early retirement. While published data characterize risk factors for failure to return to work following HCT, information on how centers advise and/or facilitate the return to work (RTW) transition for their post-HCT patients is lacking. We aimed to determine 1) whether transplant centers have guidelines for RTW post-HCT and the details of these guidelines and 2) whether transplant centers have RTW support programs for their patients and what these programs entail. Methods We used emailed links to an anonymous REDcap secure web application to distribute surveys with questions regarding RTW guidelines and support programs to 150 transplant center directors within and outside the United States. Centers were selected if they performed at least 50 HCTs per year. The survey contained 32 closed-ended questions as well as the opportunity to provide write-in responses. Results We received 45 completed surveys (30% response rate) from 27 transplant center directors, 6 physicians, 2 advanced practice providers, and 9 others. Thirty-six (80%) responders had been in the transplant field at least 10 years. While 39 (87%) participants endorsed that RTW is a problem for post-HCT patients, only 16 (36%) responded that they have RTW support for their patients and 3 had formal RTW support programs. Thirty-nine responders (87%) endorsed that a RTW program would be somewhat helpful (n = 16) or very helpful (n = 23) for their patients. Responders thought psychosocial counseling (n= 40), physical therapy (n = 33), vocational rehabilitation (n = 26) and interfacing with patient's employers (n = 23) would benefit their patients. Fifty-one percent thought the program should begin when the patient's condition warrants rather than at a set time-point. Twenty (44%) responders reported having RTW guidelines for their post-HCT patients. While 70% of the centers' guidelines recommended that autologous HCT recipients RTW between 1-3 months post-HCT, 85% of the centers' guidelines endorse that allogeneic HCT recipients postpone RTW until 6-12 months post HCT. Guidelines also varied depending on whether the patient was still on immune suppression and what type of work they did pre-HCT. Jobs involving children (60%), sick people (66%) and animals (47%) were considered to be the highest risk professions for RTW. Centers that did not have guidelines noted that they make RTW recommendations on a case-to-case basis. Conclusions While the majority of responders agreed that RTW is a problem for post-HCT patients, consistent guidelines and RTW support for post-HCT patients are lacking. Efforts toward creating standardized guidelines and RTW support programs are much needed and ongoing.

Hematopoietic cell transplantation (HCT) is a complex procedure that requires availability of adequate infrastructure, personnel, and resources at transplantation centers. We conducted a national survey of transplantation centers in the United States to obtain data on their personnel, infrastructure, and care delivery models. A 42-item web-based survey was administered to medical directors of transplantation centers in the United States that reported any allogeneic HCT to the Center for International Blood and Marrow Transplant Research in 2011. The response rate for the survey was 79% for adult programs (85 of 108 centers) and 82% for pediatric programs (54 of 66 centers). For describing results, we categorized centers into groups with similar volumes based on 2010 total HCT activity (adult centers, 9 categories; pediatric centers, 6 categories). We observed considerable variation in available resources, infrastructure, personnel, and care delivery models among adult and pediatric transplantation centers. Characteristics varied substantially among centers with comparable transplantation volumes. Transplantation centers may find these data helpful in assessing their present capacity and use them to evaluate potential resource needs for personnel, infrastructure, and care delivery and in planning for growth.

The use of large databases has provided advancements in the understanding of racial, ethnic, and socioeconomic disparities in the field of adult hematopoietic cell transplants (HCT). Disparities exist on individual, institutional, and systemic levels for both allogeneic and autologous HCT. We reviewed the most recent publications that utilized large databases to elucidate disparities in HCT and placed them into historical context of the other major studies in the field. Two emerging themes were identified. These themes are persistent inequalities in both allogeneic HCT and autologous HCT for myeloma and the importance of improving homogeneity of care in HCT. Minimization of inequalities can be achieved only with an understanding of the persistent barriers that exist in the field.

The role of hematopoietic cell transplantation (HCT) in the therapy of Hodgkin lymphoma (HL) in pediatric and adult patients is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are included and were reached unanimously by a panel of HL experts. Both autologous and allogeneic HCT offer a survival benefit in selected patients with advanced or relapsed HL and are currently part of standard clinical care. Relapse remains a significant cause of failure after both transplant approaches, and strategies to decrease the risk of relapse remain an important area of investigation.

OBJECTIVE Second allogeneic hematopoietic cell transplantation (HCT) may be indicated following relapse or graft failure following first HCT. Our retrospective single-center study sought to investigate parameters that influence post-second allogeneic HCT survival. METHOD We investigated 92 patients who underwent second allogeneic HCT between 1980 and 2016 for relapse or graft failure following first HCT. Median age at second HCT was 41 years (range 16-68), performed for relapse in 59 patients (64%) and for graft failure in 33 patients (36%). RESULTS On univariate analysis, 3-year OS of the entire cohort was 35% (95% CI=25-45). Eastern Cooperative Oncology Group (ECOG) score (3-year OS 48% for ECOG 0-1, 18% for ECOG 2-3, P=.0006), second HCT indication (3-year OS 43% for relapse, 20% for graft failure, P=.02), time from first HCT to relapse/graft failure (3-year OS for

The present study aimed to investigate baseline and posttransplant prognostic factors for allogeneic hematopoietic cell transplantation (HCT) in 61 lymphoma patients. The 5-year probabilities of overall survival (OS), non-relapse mortality (NRM), progression-free survival (PFS), and event-free survival (EFS) were 31.1%, 28.8%, 38.8%, and 23.2%, respectively. Multivariate analysis demonstrated that the International Prognostic Index risk at HCT was a significantly independent prognostic factor for OS, NRM, PFS, and EFS, and chemosensitivity was a prognostic factor for OS, NRM, and EFS. The occurrence of chronic graft-versus-host disease (GVHD) was significantly associated with higher OS, but it was not with PFS or EFS. Various parameters of immune reconstitution at 1 month after transplantation were associated with clinical outcomes in different ways. Our study results might be helpful in selecting appropriate patients or adopting effective posttransplant treatment strategies, eventually leading to an improvement in outcomes after allogeneic HCT for lymphoma.

For younger patients with intermediate- or high-risk acute myeloid leukemia (AML) in first remission, allogeneic hematopoietic cell transplantation (HCT) offers the best chance of cure and therefore is the treatment of choice. The role of allogeneic HCT in the treatment of older patients is less well defined. In this review, four issues concerning the role of HCT in the treatment of older AML patients will be addressed: the frequency of allogeneic HCT in the older AML population in the US; the impact of age on the outcome of HCT; the comparative outcome of allogeneic HCT versus chemotherapy in older AML patients; and some of the barriers to the effective use of HCT in older AML patients.

Background ETS2 is a downstream effector of the RAS/RAF/ERK pathway, which plays a critical role in the development of malignant tumor. However, the clinical impact of ETS2 expression in AML remains unknown. Methods In this study, we evaluated the prognostic significance of ETS2 expression using two relatively large cohorts of AML patients. Results In the first cohort, compared to low expression of ETS2 (ETS2 low), high expression of ETS2 (ETS2 high) showed significant shorter OS, EFS and RFS in the current treatments including the allogeneic HCT group (n = 72) and the chemotherapy group (n = 100). Notably, among ETS2 high patients, those received allogeneic HCT had longer OS, EFS and RFS than those with chemotherapy alone (allogeneic HCT, n = 39 vs. chemotherapy, n = 47), but treatment modules play insignificant role in the survival of ETS2 low patients (allogeneic HCT, n = 33 vs. chemotherapy, n = 53). Moreover, gene/microRNA expression data provides insights into the biological changes associated with varying ETS2 expression levels in AML. The prognostic value of ETS2 was further validated in the second AML cohort (n = 329). Conclusions Our results indicate that ETS2 high is a poor prognostic factor in AML and may guide treatment decisions towards allogeneic HCT. Electronic supplementary material The online version of this article (doi:10.1186/s12967-017-1260-2) contains supplementary material, which is available to authorized users.

Allogeneic hematopoietic cell transplantation (HCT) is the most potent therapy for preventing relapse of acute myeloid leukemia (AML). Although its efficacy is compromised by a high risk of treatment-related morbidity and mortality, an accumulating body of evidence has led to the general recommendation favoring allogeneic HCT from a matched sibling donor during first complete remission (CR1) for younger patients with cytogenetically intermediate- or high-risk AML. Over the past few decades, this field has seen a great many advancements. The indications for allogeneic HCT have been refined by taking into account the molecular profiles of leukemic cells and the degree of comorbidities. The introduction of high-resolution human leukocyte antigen-typing technology and advances in immunosuppressive therapy and supportive care measures have improved outcomes in alternative donor transplantation, while the parallel growth of unrelated donor registries and greater use of umbilical cord blood and haploidentical donors have considerably improved the chance of finding an alternative donor. The development of reduced-intensity and non-myeloablative conditioning has made it possible to receive allogeneic HCT for patients who might once have been considered ineligible due to advanced age or comorbidities. Thanks to these advances, the role of allogeneic HCT during CR1 has become progressively more important in the treatment of AML.

The original version of this article contained a mistake in fig. 1a. "Autologous HCT(n=111)" should be changed to "Allogeneic HCT (n=51)". Correct figure is presented below.

Objective To review and summarize nurses’ roles in the care of the older adult undergoing an allogeneic hematopoietic cell transplant (HCT) for the treatment of leukemia. Data Sources Published literature indexed in PubMed, CINAHL, textbooks, and clinical expertise. Conclusion Nurses are a vital component of the highly specialized care delivered before, during, and after an allogeneic HCT. Implications for Nursing Practice Nurses who are prepared for the complex HCT care trajectory will be able to optimally meet the complex needs of the older adult patient and their caregiver(s).

Acute graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic cell transplantation and is the primary cause of early non-relapse mortality (NRM) after transplant. GVHD of the gastrointestinal (GI) tract fuels the systemic inflammatory reaction and consequently is the principal driver of mortality. Recently, the MAGIC algorithm probability (MAP) that is computed from two biomarkers of GI GVHD has been validated to accurately predict risk of NRM throughout the course of early acute GVHD. This review focuses on the biology, clinical evidence, and practical application of the biomarkers in the measurement of acute GVHD.

Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT–comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range

Background Letermovir (LET) is approved for the prophylaxis of cytomegalovirus (CMV) in allogeneic hematopoietic cell transplantation (allo-HCT) patients. LET is a weak-moderate CYP3A4 inhibitor, which may impact calcineurin inhibitor (CNI) levels. In the phase 1 trial, LET caused an increase in maximum plasma concentrations (Cmax) of CSA and tacrolimus by 37% and 70%, respectively. There are no data to correlate how the Cmax increase in the presence of LET may affect CNI trough levels. Methods A retrospective review was conducted to evaluate the effect of LET on CNI trough levels and determine if empiric dose adjustments are needed. Patients ≥ 18 years were included if they received an allo-HCT with a CNI from February to June 2018 and received LET 480 mg daily or 240mg daily for tacrolimus- or CSA-based GVHD prophylaxis, respectively. The primary endpoint was percent change in concentration to dose (C/D) ratio over the 7-day period after initiation of LET. The C/D ratio allows for an analysis of the effect on trough levels at any given dose, which we would expect to rise upon initiation of LET due to CYP inhibition. LET reaches steady state in 36-60 hours; therefore, C/D percent changes were evaluated both from baseline to 4 days post-LET and from day 4 to day 7. Results Thirty-four patients (median age 53, range 24-75) were included in the analysis, with 24 (70.6%) patients receiving a tacrolimus-based graft-versus-host disease (GVHD) prophylaxis and 10 (29.4%) patients receiving CSA-based GVHD prophylaxis. There were 8 (24%) umbilical cord blood transplants, 10 (29%) haploidentical HCTs, and 16 (47%) conventional HCTs, with 14 patients (41%) receiving myeloablative conditioning. LET was initiated on a median of day 7 (range 6-30) post-HCT, and 23 patients (68%) received the drug orally. In the 10 patients who received CSA, there was an average of 3.8 (range 1-6) dose changes over 7 days. From baseline to 4 days post-LET, the mean percent change in C/D ratio was +15.9%, with a subsequent -10.0% change in C/D ratio from day 4 to day 7. In the 24 patients who received tacrolimus, there was an average of 2.2 (range 0-5) dose changes over 7 days. From baseline to 4 days post-LET, the mean percent change in C/D ratio was +20.4%, with a subsequent -18.9% change in C/D ratio from day 4 to day 7. Days 0 to 7 trough levels for all patients are displayed in Figures 1 and 2. Conclusion An empiric dose reduction in CNIs upon initiation of LET does not appear to be warranted based on this pilot study. An increase in trough levels is seen within 4 days after initiation of LET; however, the increase seems marginal and is compensated for by adjusting doses based on levels, which is the standard of care. Larger studies are needed to assess additional factors that may affect this drug-drug interaction.

BACKGROUND In adults, the 2 main types of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML). Both are associated with a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) is the only known curative treatment modality for these diseases, but data on outcomes following such treatment are limited. We analyzed the outcomes of patients with MDS/MPN after allogeneic HCT. METHODS This retrospective study included 10 patients with MDS/MPN who received allogeneic HCT at Asan Medical Center from 2002 to 2010. Of these 10 patients, 7 had CMML, 2 had aCML, and 1 had unclassifiable MDS/MPN. Five patients received a myeloablative conditioning (MAC) regimen (busulfan-cyclophosphamide), and 5 received reduced-intensity conditioning (RIC) regimen. RESULTS Neutrophil engraftment was achieved in all patients. After a median follow-up of 47.5 months among surviving patients, 4 had relapsed and 5 had died. There was only 1 treatment-related death. The 5-year rates of overall, relapse-free, and event-free survival were 42.2%, 51.9%, and 46.7%, respectively. Relapse was the leading cause of treatment failure, and all relapses were observed in patients who had received RIC and who did not develop chronic graft-versus-host disease. CONCLUSION Allogeneic HCT can induce durable remission in patients with MDS/MPN, but RIC cannot replace MAC in patients eligible for myeloablative treatments.

Although the role of autologous hematopoietic cell transplantation (auto-HCT) is well established in neuroblastoma (NBL), the role of allogeneic HCT (allo-HCT) is controversial. The Center for International Blood and Marrow Transplant Research conducted a retrospective review of 143 allo-HCT for NBL reported in 1990-2007. Patients were categorized into two different groups: those who had not (Group 1) and had (Group 2) undergone a prior auto-HCT (n=46 and 97, respectively). One-year and five-year OS were 59% and 29% for Group 1 and 50% and 7% for Group 2, respectively. Among donor types, disease-free survival (DFS) and OS were significantly lower for unrelated transplants at 1 and 3 years but not at 5 years post HCT. Patients in CR or very good partial response (VGPR) at transplant had lower relapse rates and better DFS and OS, compared with those not in CR or VGPR. Our analysis indicates that allo-HCT can cure some neuroblastoma patients, with lower relapse rates and improved survival in patients without a history of prior auto-HCT as compared with those patients who had previously undergone auto-HCT. Although the data do not address why either strategy was chosen for patients, allo-HCT after a prior auto-HCT appears to offer minimal benefit. Disease recurrence remains the most common cause of treatment failure.

Aim: We conducted a retrospective review of all brain imaging studies in the first year after allogeneic haematopoietic cell transplantation (HCT) to determine (a) the percentage of patients with CNS neurological complications based solely on undergoing brain imaging, (b) transplant-related risk factors of undergoing brain imaging, and (c) overall survival in the patients with neurological complications compared to those transplant patients who did not have brain imaging. Methods: Subjects were 543 consecutive recipients (August 2004-August 2007) of allogeneic HCT followed for overall survival for up to 6 years after HCT. Comparisons between patient groups with brain imaging and without brain imaging were tested using the Pearson chi-square test. Survival analyses with outcome time-to-brain-scan started at date of transplant and used Kaplan-Meier methods. Results: Of 543 HCT recipients, 128 patients (24%) underwent brain imaging during the first year after transplantation. There was a greater risk of brain imaging in unrelated donor transplants and in lymphoid as opposed to myeloid malignancies (respective hazard ratios 1.45 and 1.43, P=0.04). Overall survival was significantly worse in unrelated donor transplants (hazard ratio 1.42, P=0.003) and in cord blood transplants (hazard ratio 1.68, P=0.02). Landmark survival analysis of patients alive 1 year after HCT showed worse survival over the next 5 years in those who had brain imaging in the first post transplant year (P

Objective Multidrug-resistant organisms (MDRO) are a challenge in allogeneic hematopoietic cell transplantation (HCT). However, in the literature there is no comprehensive analysis on MDRO in HCT. In this retrospective, single-center analysis, we appraised prevalence and clinical impact of MDRO in 98 consecutive allogeneic HCT patients. Method Prior to the conditioning (baseline) and whenever clinically indicated patients underwent a full screening for MDRO (stool and urine cultures, swabs from several body regions). Results It turned out that 26 patients were colonized by 33 MDRO, either at baseline (n=16) or at any other time until day 100 post-transplantation. Of these 26 patients, eight developed an infection with MDRO, four of them by 4MRGN Pseudomonas aeruginosa, and three of them died MDRO-related. However, there was no significant difference between MDRO-colonized and non-colonized patients regarding overall survival (OS) and non-relapse-mortality (NRM). There was only a trend toward a higher NRM in patients already colonized by MDRO at baseline. This was due to the high NRM in multidrug-resistant P. aeruginosa-colonized patients. Conclusion In summary, colonization with MDRO other than P. aeruginosa had no negative impact on NRM and OS. Patients colonized by multidrug-resistant P. aeruginosa had a dismal outcome. HCT of these patients should be considered with care. Screening for MDRO in the pretransplant work-up is suggested.

Acute GvHD remains a major cause of hematopoietic cell transplant (HCT)-related mortality. aGvHD represents the primary limitation to more widespread use of allogeneic HCT as a potentially curative modality for patients with malignant and non-malignant diseases. Two main approaches may improve the outcomes of patients with aGvHD: the ability to diagnose the disease in a timely manner, or even predict aGvHD prior to clinical manifestation (Figure 1), along with the accurate stratification of these patients (Figure 2). Secondly, novel therapeutic targets are desperately needed as no treatment to date added to upfront steroids has proven beneficial.

Myelodysplastic syndromes (MDS) comprise aheterogeneousgroupofclonalhematopoietic stem-cell disorders that result in varying degrees of cytopenia and risk of transformation intoacute leukemia.Allogeneichematopoietic cell transplantation (HCT) is the only known curative therapy for this disease. Before August 2010, most patients with MDS in the United States were not considered for allogeneic HCT because they were older than 65 years of age and Medicare had never declared allogeneic HCT a covered benefit for its patient population. OnAugust 4, 2010, the Centers for Medicare & Medicaid Services released its Decision Memo for Allogeneic Hematopoietic StemCell Transplantation (HSCT) for Myelodysplastic Syndrome. This memo states: “Allogeneic HSCT for MDS is covered by Medicare only for beneficiaries with MDS participating in an approved clinicalstudythatmeets thecriteriabelow...” Since that decision was made, the number of allografts performed in the United States for MDS has nearly tripled. Thus the review by Bhatt and Steensma is particularly timely, and the authors should be commended on their thoroughness and for a balanced discussion. In the next few paragraphs, I will underscore the most important points from their review as well as areas that require further discussion.

Hematopoietic cell transplantation (HCT) is a widely used treatment modality for malignant and nonmalignant hematologic diseases. Both autologous and allogeneic HCT produce substantial periods of immunosuppression and predispose recipients to a variety of common and opportunistic infections. In allogeneic HCT recipients, the development of chronic graft-vs.-host disease, which can persist for years, leads to long-lasting immunocompromise. Infection is a major cause of morbidity and mortality in HCT recipients. This chapter reviews the basic principles of HCT, with a focus on the effects of transplantation on the immune system and on the process of immune reconstitution after HCT.

Although allogeneic hematopoietic cell transplantation (HCT) from a related donor is effective therapy for younger patients with AML, it remains unknown how the availability of a related donor affects the outcome when unrelated HCT is a treatment option for patients without a related donor. To address this issue, we retrospectively analyzed 605 cytogenetically non-favorable AML patients younger than 50 years for whom a related donor search was performed during first CR (CR1). The 4-year OS was 62% in 253 patients with a related donor and 59% in 352 patients without a related donor (P=0.534). Allogeneic HCT was performed during CR1 in 62% and 41% of patients with and without a related donor, respectively. Among patients transplanted in CR1, the cumulative incidence of non-relapse mortality was significantly higher in patients without a related donor (P=0.022), but there was no difference in post-transplant OS between the groups (P=0.262). These findings show the usefulness of unrelated HCT in younger patients with cytogenetically non-favorable AML who do not have a related donor. The extensive use of unrelated HCT for such patients may minimize the potential disadvantage of lacking a related donor.

Peripheral blood stem cells (PBSCs) are increasingly used as the graft source in allogeneic hematopoietic cell transplantation. We compared long-term outcome after unrelated donor transplantation of 85 consecutive patients with acute myelogenous leukemia or myelodysplastic syndrome regarding disease status (early disease [CR1, refractory anemia); n = 25 and advanced/active disease [>CR1, >refractory anemia]; n = 60) who were treated with conventional conditioning regimens followed by bone marrow (BM) or PBSC grafts. Graft-versus-host disease prophylaxis consisted mainly of cyclosporine A, short-course methotrexate, and anti-T-lymphocyte globulin. After a median follow-up of 118 months (68-174), the 10-year event-free survival rate after peripheral blood stem cell transplantation (PBSCT) was 54.8% (95% confidence interval [CI], 39.7%-69.8%), and after bone marrow transplantation (BMT), it was 27.9% (14.5%-41.3%; P < .004). In the advanced/active disease group, the 10-year event-free survival rate after PBSCT was 50% (30.8%-69.2%), and after BMT, it was 23.5% (9.3%-37.8%; P < .007). Non relapse mortality was less after PBSCT than BMT (14.3% vs 30.2%), respectively. In multivariate Cox regression analysis, PBSCT showed a better overall survival (OS; hazard ratio [HR], 0.43; 95% CI, 0.23-0.79; P = .007) compared to BMT; unfavorable/unknown prognostic impact cytogenetic abnormalities were an adverse factor for all patients (HR, 2.202; 95% CI, 1.19-4.06; P = .011). In patients with advanced disease, the use of PBSCs showed a significant favorable outcome via multivariate analysis (HR, 0.49; 95% CI, 0.24-0.99; P = .046). Outcome of acute myelogenous leukemia/myelodysplastic syndrome after unrelated hematopoietic cell transplantation is adversely affected by cytogenetic abnormalities and state of remission at hematopoietic cell transplantation. PBSC as a graft source has a significant favorable influence on survival.