Current state of nonengrafting donor leukocyte infusion (focus on microtransplantation for acute myeloid leukemia) Purpose of review Microtransplantation (or micro-stem cell transplantation, MST) is one permutation of alloreactive immunotherapy increasingly studied in clinical trials. It is most commonly applied to patients with myeloid malignancies who are not suitable candidates for allogeneic hematopoietic cell transplantation. This review highlights the past 2 years of work on stem/progenitor cell products in the field of nonengrafting donor leukocyte infusion (NE-DLI), with a focus on applications of MST in acute myeloid leukemia (AML). Recent findings Assessing the utility of MST is hampered by lack of randomized controlled trials and by variability in donor selection algorithms, treatment timing, and unknown factors. The inherent complexity of the bidirectional alloreactive reactions, implicating many cell types, makes it challenging to move beyond correlative, population-level biology toward mechanistic explanations for MST's actions in any given patient–donor pair. Yet there are indicators that by stimulating a recipient-vs.-tumor effect, MST might substantially improve complete remission rates in AML and that it might find a role in postremission therapy. Summary The mechanistic underpinnings of MST are gradually being disentangled and its clinical development remains in early stages.

MICROtransplant to refractory acute myeloid leukemia in Egyptian population Purpose of review The purpose of this review is to outline Egyptian experience of nonengraftment haploidentical cellular therapy [microtransplantation (MST)] for patients with refractory acute myeloid leukemia. Recent findings The use of granulocyte colony-stimulating factor primed halo-identical MST appears to be a biologically active therapy in patients with refractory acute myeloid leukemia (AML), especially in patients received less than four previous chemotherapy lines, fludarabine-free previous chemotherapy, response naïve and young age patients. Summary Refractory AML is still challenging. MST is promising, however the optimum conditioning, stem-cell dose, matching degree are factors should be optimized.

Is autologous stem cell transplantation still relevant for multiple myeloma? Purpose of review Autologous stem cell transplantation has been the standard of care in myeloma treatment for many years, but the availability of newer antimyeloma drugs and the emerging data from chimeric antigen receptor (CAR) T-cell clinical studies make us question the relevance of it. The purpose of this review is to go over recent data and to reassess the current status of autologous stem cell transplantation as a standard of care. Recent findings Autologous stem cell transplantation can be safely performed for elderly patients and there is no absolute age limit. Recent data on BEAM (Carmustine, Etoposide, Cytarabine, and Melphalan), Busulfan/Melphalan, and Carmustine/Melphalan conditioning when compared with Melphalan showed favorable survival outcomes with manageable toxicities although we need to see data from randomized, multicenter studies. Posttransplant maintenance and consolidation can maximize the benefit of transplant by prolonging progression-free survival. Current B-cell maturation antigen CAR T-cell therapy showed remarkably high response rates, but didn’t seem to provide durable response yet. Summary Recent advances in myeloma therapy and autologous stem cell transplantation are described. Although we’ve seen many new developments including CAR T-cell therapies, autologous stem cell transplantation remains as the standard of care. However, it may be replaced by or combined with newer therapies in the future.

Application of stem cell transplantation in autoimmune diseases Purpose of review Autologous hematopoietic stem cell transplantation (HSCT) is a promising therapeutic modality for severe autoimmune diseases. In this review, we will outline the immunological mechanisms and the clinical evidence and experiences for therapeutic HSCT in autoimmune diseases, with particular focus on systemic sclerosis and multiple sclerosis. Recent findings Approximately 3000 patients with autoimmune diseases worldwide have been treated with HSCT. HSCT in systemic sclerosis has been shown in three randomized controlled trials to be associated with significant long-term event-free survival despite some transplant-related mortality in the first year. A recent controlled trial in multiple sclerosis has also show benefit with transplant. Summary The aim of HSCT is to ‘reset’ one's immune system into a naïve and self-tolerant state through immune depletion and regulation. HSCT requires careful patient selection, close collaboration between physicians and expertise of transplant team to ensure optimal outcome.

Allogenic hematopoietic stem cell transplantation in sickle cell disease Purpose of review Discussing the currently available HSCT options for Hb SS patients highlighting advantages and disadvantages of each modality in the light of recently published data. Recent findings When MSD is available, myeloablative regimen is the preferred approach for otherwise healthy children whereas the nonmyeloablative (NMA) regimen is of choice for adults as well as children with SCD-associated morbidities. Mixed chimerism is common especially with NMA conditioning and is usually enough for cure. Alternative donor HSCT outcomes are progressively improving especially with posttransplant cyclophosphamide for GVHD prophylaxis. Summary Recent studies comparing HSCT and chronic transfusion in Hb SS patients increasingly come in favor of HSCT arm. Advances in HSCT field led to donor pool expansion and better tolerated regimens. It is easier now to tailor a personalized transplantation plan for almost every patient. A successful management plan should be sufficiently comprehensive addressing patients’ and families’ social and psychological concerns to ensure compliance and improve outcome.

Recent progress in haploidentical transplantation: is this the optimal choice for alternative donor transplantation? Purpose of review This article is intended to review recent trends and improvements in haploidentical transplantation to understand its current status and future direction. Recent findings The noninferiority of haploidentical donors compared with other donor sources, including HLA-matched related or unrelated donors, has been demonstrated in patients with various hematological diseases. The development of graft-versus-host-disease (GVHD) prophylaxis using posttransplant cyclophosphamide has effectively reduced transplant-related mortality caused by GVHD, graft rejection, and other related complications. Novel GVHD prophylactic methods and other supportive strategies are under intense investigation to reduce the risk of infections and retain graft-versus-leukemia/lymphoma effects after transplantation. Summary Recent progress in haploidentical stem cell transplantation has broadened the availability of donor sources for patients with hematological diseases. It is important to compare and examine the impact of donor sources on transplant outcomes to achieve a better understanding about the appropriate donor choice for each patient.

Using minimal (measurable) residual disease assessments to guide decision-making for timing of allogeneic transplantation in acute myeloid leukemia Purpose of review The current review aims to highlight recent and important developments in the detection and value of minimal (measurable) residual disease (MRD) testing in patients with acute myeloid leukemia (AML) and the impact on the timing of allogeneic hematopoietic cell transplantation. Recent findings The European LeukemiaNet MRD Working Party recently published guidelines to help standardize testing, utilizing flow cytometry and molecular techniques. The timing of MRD assessments, choice of assay and cutoff of for reporting positive results are all important. Patients known to be MRD-positive pretransplantation have a poor prognosis and consideration should be given to selecting a myeloablative regimen over a reduced intensity regimen (if appropriate) and offering posttransplantation maintenance therapy. Summary It may be best to think of MRD as a dynamic variable, where a rising MRD result is more specific and highly predictive of relapse. It is unclear how MRD results should impact the timing of allogeneic hematopoietic cell transplantation, if at all. There are currently no published randomized studies to help guide the practitioner in this situation, hence decision-making should be individualized.

Current landscape for chimeric antigen receptor T cells in lymphomas Purpose of review CART cell therapy has changed the treatment landscape for relapsed/refractory aggressive lymphomas. In this article, we review the CART constructs most studied in lymphoma and their applicability. Recent findings Results of ZUMA-1, JULIET and TRANSCEND trials will be reviewed. Real-world data will also be reviewed. Summary CART cell therapy is evolving and becoming safer. Increased uptake of this modality outside of clinical trials is expected.

Mechanisms of failure of chimeric antigen receptor T-cell therapy Purpose of review Although chimeric antigen receptor T (CART)-cell therapy is best recognized for its antitumor effect in relapsed/refractory B-cell hematological cancers, it is still associated with a high relapse rate. Recent findings We firstly analyzed internal immunological and genetic reasons of CD19+ relapse after treatment for R/R B-cell hematological cancers with CART19 cells. The reasons: murine-derived scFv may limit expansion of CART cells. Repeated antigen exposure leads to T-cell exhaustion. Activation of T cells can cause T-cell senescence and high expression of inhibitive receptors, PD-1, CTLA4, TIGIT, LAG-3, CD244, CD160, TIM3, which might be solved by some external pharmacological intervention methods [for instance, the use of FC (Fludarabine, Cyclophosphamide) lymphodepletion regimen, lenalidomide, PD-1 inhibitor, ibrutinib and humanized CD19-CART cells. Secondly, mechanism of CD19 relapse can be attributed to the preexisting of CD19- subclone, the loss or alternative RNA splicing on exon 2 of chromosome 16 on which CD19 gene is located, B-cell transcript factors – paired-box 5 (PAX5) and early B-cell factor 1 (EBF1) are down-regulated to cause lineage-switch from lymphoid to myeloid. Summary Although different preparation techniques generates various entities of CART 19 cells, these problems could be conquered by novel agents and novel CAR system. Video abstract Although Chimeric Antigen Receptor T (CART) cell therapy is best recognized for its antitumor effect in Relapsed/Refractory B-cell hematological cancers, it still shows a high relapse rate. We review mechanisms of failure of CART therapy. http://links.lww.com/COH/A18.