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On the basis of the data suggesting that adolescents and young adult patients with acute lymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric protocols, we assessed the feasibility of treating adult patients aged 18–50 years with ALL with the DFCI Pediatric ALL Consortium regimen utilizing a 30-week course of pharmacokinetically dose-adjusted E. coli L-asparaginase during consolidation. Between 2002 and 2008, 92 eligible patients aged 18–50 years were enrolled at 13 participating centers. Seventy-eight patients (85%) achieved a complete remission (CR) after 1 month of intensive induction therapy. With a median follow-up of 4.5 years, the 4-year disease-free survival (DFS) for the patients achieving a CR was 69% (95% confidence interval (CI) 56–78%) and the 4-year overall survival (OS) for all eligible patients was 67% (95% CI 56–76%). The 4-year DFS for the 64 patients who achieved a CR and were Philadelphia chromosome negative (Ph−) was 71% (95% CI 58–81%), and for all 74 Ph− patients the 4-year OS was 70% (95% CI 58–79%). We conclude that a pediatric-like treatment strategy for young adults with de novo ALL is feasible, associated with tolerable toxicity, and results in improved outcomes compared with historical regimens in young adult patients with ALL.

Umbilical cord blood (UCB) is a graft source for patients with malignant or genetic diseases who can be cured by allogeneic hematopoietic cell transplantation (HCT), but who do not have an appropriately HLA-matched family or volunteer unrelated adult donor. Starting in the 1990s, unrelated UCB banks were established, accepting donations from term deliveries and storing UCB units for public use. An estimated 730 000 UCB units have been donated and stored to date and ∼35 000 UCB transplants have been performed worldwide. Over the past 20 years, private and family banks have grown rapidly, storing ∼4 million UCB units for a particular patient or family, usually charging an up-front and yearly storage fee; therefore, these banks are able to be financially sustainable without releasing UCB units. Private banks are not obligated to fulfill the same regulatory requirements of the public banks. The public banks have released ∼30 times more UCB units for therapy. Some countries have transitioned to an integrated banking model, a hybrid of public and family banking. Today, pregnant women, their families, obstetrical providers and pediatricians are faced with multiple choices about the disposition of their newborn’s cord blood. In this commentary, we review the progress of UCB banking technology; we also analyze the current data on pediatric and adult unrelated UCB, including the recent expansion of interest in transplantation for hemoglobinopathies, and discuss emerging studies on the use of autologous UCB for neurologic diseases and regenerative medicine. We will review worldwide approaches to UCB banking, ethical considerations, criteria for public and family banking, integrated banking ideas and future strategies for UCB banking.

The aim of this work is to produce recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles released from 1999 to 2015 (January) was used as a source of scientific evidence. Recommendations were produced using a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet and European Blood and Marrow Transplantation Group. Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention and management of relapse after transplant. Patients with intermediate-2- or high-risk disease and age <70 years should be considered as candidates for allo-SCT. Patients with intermediate-1-risk disease and age <65 years should be considered as candidates if they present with either refractory, transfusion-dependent anemia, or a percentage of blasts in peripheral blood (PB) >2%, or adverse cytogenetics. Pre-transplant splenectomy should be decided on a case by case basis. Patients with intermediate-2- or high-risk disease lacking an human leukocyte antigen (HLA)-matched sibling or unrelated donor, should be enrolled in a protocol using HLA non-identical donors. PB was considered the most appropriate source of hematopoietic stem cells for HLA-matched sibling and unrelated donor transplants. The optimal intensity of the conditioning regimen still needs to be defined. Strategies such as discontinuation of immune-suppressive drugs, donor lymphocyte infusion or both were deemed appropriate to avoid clinical relapse. In conclusion, we provided consensus-based recommendations aimed to optimize allo-SCT in PMF. Unmet clinical needs were highlighted.

Neurologic complications (NCs) may be a significant source of morbidity and mortality after hematopoietic cell transplantation (HCT). We performed a retrospective study of 263 consecutive patients undergoing allogeneic HCT for hematological malignancies to determine the incidence, risk factors and clinical impact of NCs in the first 5 years after HCT. We determined the incidence of central nervous system (CNS) infection, intracranial hemorrhage, ischemic stroke, metabolic encephalopathy, posterior reversal encephalopathy syndrome, seizure and peripheral neuropathy. In all, 50 patients experienced 63 NCs—37 early (⩽day +100), 21 late (day +101 to 2 years) and 5 very late (2 to 5 years). The 1- and 5-year cumulative incidences of all NCs were 15.6% and 19.2%, respectively, and of CNS complication (CNSC; all of the above complications except peripheral neuropathy) were 12.2 and 14.5%. Risk factors for CNSC were age (hazard ratio (HR)=1.06 per year, P =0.0034), development of acute GvHD grade III–IV (HR=2.78, P =0.041), transfusion-dependent thrombocytopenia (HR=3.07, P =0.025) and delayed platelet engraftment (>90th centile; HR=2.77, P =0.043). CNSCs negatively impacted progression-free survival (HR=2.29, P =0.0001), overall survival (HR=2.63, P <0.0001) and non-relapse mortality (HR=8.51, P <0.0001). NCs after HCT are associated with poor outcomes, and usually occur early after HCT.

Little is known about how patients undergoing hematopoietic stem cell transplantation (HCT) and their family caregivers (FC) perceive their prognosis. We examined prognostic understanding in patients undergoing HCT and their FC and its relationship with quality of life (QOL) and mood. We conducted a longitudinal study of patients (and FC) hospitalized for HCT. We used a questionnaire to measure participants’ prognostic understanding and asked the oncologists to estimate patients’ prognosis prior to HCT. We assessed QOL and mood weekly and evaluated the relationship between prognostic understanding, and QOL and mood using multivariable linear mixed models. We enrolled 90 patients undergoing (autologous ( n =30), myeloablative ( n =30) or reduced intensity allogeneic ( n =30)) HCT. About 88.9% of patients and 87.1% of FC reported it is ‘extremely’ or ‘very’ important to know about prognosis. However, 77.6% of patients and 71.7% of FC reported a discordance and more optimistic prognostic perception compared to the oncologist ( P <0.0001). Patients with a concordant prognostic understanding with their oncologists reported worse QOL ( β =−9.4, P =0.01) and greater depression at baseline ( β =1.7, P =0.02) and over time (( β =1.2, P <0.0001). Therefore, Interventions are needed to improve prognostic understanding, while providing patients with adequate psychological support.

Unfortunately, many patients referred for hematopoietic cell transplant will not have a fully matched related donor, and finding matched unrelated donors through the registry may be difficult, especially if the recipient is not of Northern European descent [N Engl J Med 2014;371:339‐348]. Umbilical cord blood (UCB) has been an available graft source for hematopoietic cell transplant for more than 30 years, since the first UCB transplant was performed in the late 1980s [N Engl J Med 1989;321:1174‐1178]. UCB is readily available, has low immunogenicity, and does not require as strict of human leukocyte antigen (HLA) matching compared to other graft sources [N Engl J Med 2004;351:2265‐2275]. According to data from the Center for International Blood and Marrow Transplant Research (CIBMTR), an estimated 500 patients in the US will have received a UCB transplant in 2018. Since 2014, haploidentical transplants have surpassed UCB transplants performed in the United States (CIBMTR Summary Slides, 2018, available at https://www.cibmtr.org). Increased use of haploidentical transplants has brought to light concerns about UCB transplants, including delayed engraftment and graft failure, increased nonrelapse mortality, increased infection risk, and UCB acquisition costs [Lancet Oncol 2010;11:653‐660; Biol Blood Marrow Transplant 2019;1456‐1464]. These concerns will need to be addressed for UCB to remain a viable option as a graft source for hematopoietic cell transplant. Other promising therapeutic benefits for UCB, in addition to hematopoietic cell transplant, is its use in regenerative medicine and immune modulation, which is currently being evaluated in ongoing clinical trials. Alternative donors, haploidentical donors and umbilical cord blood (UCB), are viable graft options for hematopoietic transplant if a patient does not have a matched related or unrelated donor. UCB is rapidly available, has low immunogenicity, and a potentially lower incidence of chronic graft vs host disease compared to other graft sources. However, UCB has several disadvantages that may impact the success of a hematopoietic transplant including delayed engraftment, graft failure, increased infection, and increased transplant‐related mortality. Ongoing studies in ex vivo expansion, homing, and combined grafts are evaluating ways to reduce or eliminate the disadvantages associated with UCB grafts and improve hematopoietic transplant outcomes.

One of the truly revolutionary advances in hematopoietic cell transplantation (HCT) is the increasingly successful use of alternative donors, thereby allowing the delivery of a potentially curative transplant to ∼75% of patients who do not have an HLA-matched sibling donor. A substantial proportion of the need has been met by HLA-matched volunteer unrelated donors, but an unmet need still exists, particularly among minority populations and for people who need a more immediate source of hematopoietic cells. Two such sources, umbilical cord blood (UCB) and haploidentical related donors, have filled most of this need, and outcomes following transplants from these donor sources are very promising. UCB has the advantages of ready availability and is less capable of causing GVHD but hematological recovery and immune reconstitution are slow. Haploidentical HCT is characterized by the nearly uniform and immediate availability of a donor and the availability of the donor for post transplant cellular immunotherapy, but is complicated by a high risk of GVHD and poor immune reconstitution when GVHD is prevented by vigorous ex vivo or in vivo T-cell depletion. This review will discuss the pertinent issues that affect the choice of one donor source over another and offer recommendations regarding the optimal utilization of these donor sources.

During human development, stem cells establish themselves in specific anatomic locations or niches. The niche harbors the stem cells, and regulates how stem cells proliferate. The interaction between stem cells and their niche affects stem cell function, and offers an opportunity to improve the marrow microenvironment. Osteoblasts produce hematopoietic growth factors and are activated by parathyroid hormone (PTH). A calcium sensing receptor, expressed by hematopoietic stem cells, regulates the niche and can be targeted to increase stem cell numbers. Therefore, drugs that affect osteoblast function or target calcium receptors may be useful for stem cell mobilization and engraftment. In this review, the biology of the stem cell niche and the potential therapeutic manipulations of the stem cell niche are reviewed. PTH is in clinical trials for patients who have not mobilized autologous stem cells well. The limiting cell numbers for adult cord blood transplantation increase the risk of infection, and PTH is currently in a clinical trial following cord blood transplantation in an effort to improve engraftment and immune reconstitution.

Allogeneic stem cell transplantation remains the only curative therapy for myelofibrosis. Despite advances in transplant, the morbidity and the mortality of the procedure necessitate careful patient selection. In this manuscript, we describe the new prognostic scoring system to help select appropriate patients for transplant and less aggressive therapies. We explore the advances in non-transplant therapy, such as with investigational agents. We review the blossoming literature on results of myeloablative, reduced intensity and alternative donor transplantation. Finally, we make recommendations for which patients are most likely to benefit from transplantation.