Allogeneic haematopoietic stem cell transplantation (allo-HCT) is the most effective curative therapy in myelodysplastic syndromes (MDS). Incidence of MDS increases with age, peaking in the seventh decade of last century. Despite improved consolidation chemotherapy regimens, the prognosis of MDS in patients beyond 60 years of age is dismal. The introduction of peripheral blood-derived stem cell grafts into allogeneic HSCT and the known anti-tumor effect of donor lymphocyte infusions paved the way for reduced-intensity conditioning (RIC) allogeneic hematopoietic stem-cell transplantation, which makes transplant possible in advanced age, significantly alleviates transplant-related organ toxicity and decreases non-relapse mortality. This article reviews the advanced development of reduced-intensity conditioning regimens in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes and the future of reduced intensity conditioning hematopoietic stem cell transplants including feasibility of RIC allo-HSCT in treating patients with MDS, selection of MDS cases for RIC allo-HSCT, opportunity of RIC allo-HSCT, source of stem cells for RIC allo-HSCT, RIC regimen for allo-HSCT, evaluation of curative efficacy and prognosis, GVHD and graft versus MDS, and so on.
Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Myelodysplastic Syndromes ; therapy ; Transplantation Conditioning ; methods ; Transplantation, Homologous

Adult ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Primary Myelofibrosis ; surgery ; Transplantation Conditioning ; methods

Hematopoietic stem cell transplantation (HSCT) is the only way to cure myelodysplastic syndromes. At present there are several myelodysplastic syndromes scoring systems, including the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS) and Simplified MDS Risk Score. These score systems can not only predict the probability of transplant success, but also help to determine the time of transplantation. For the older patient with serious complication, a suitable conditioning regimen can lower the risk of treatment-related mortality. Complication management, individualized conditioning regimen, optimal timing of transplantation and donor selection should improve the curative effect of HSCT. However, post-transplantation relapse and graft-versus-host disease (GVHD) remain to be solved and further investigations are needed. In this review the MDS scoring system, factors influencing HSCT efficacy, the selection of HSCT donors and timing, the preconditioning intensity before HSCT and evaluation of HSCT efficacy are summarized.
Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Myelodysplastic Syndromes ; surgery ; Transplantation Conditioning ; methods ; Treatment Outcome

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory clinical syndrome of uncontrolled immune response which results in hypercytokinemia due to underlying primary or secondary immune defect. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only cure therapy for primary HLH and recurrent/refractory hemophagocytic lymphohistiocytosis. Compared with children HLH, adult HLH is a much more heterogeneous syndrome requiring a more individualized protocol depending on the underlying trigger, disease severity and genetic background. At present, there remain controversies in various aspects including indications of haematopoietic cell transplantation (HCT), conditioning regimen, efficacy and prognosis. This article will review the recent advances of allo-HSCT in the treatment of adult HLH based on the above issues.
Child ; Humans ; Adult ; Lymphohistiocytosis, Hemophagocytic/therapy* ; Hematopoietic Stem Cell Transplantation ; Transplantation Conditioning/methods*

Adolescent ; Adult ; Busulfan ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Middle Aged ; Transplantation Conditioning ; methods ; Young Adult

This study was aimed to investigate the efficacy of haploidentical hematopoietic stem cell transplantation (hi-HSCT) combined with umbilical cord mesenchymal stem cells (MSC) using modified conditioning regimen for the treatment of patients with refractory and relapsed or high risk malignant hematologic diseases, the clinical efficacy in 30 patients with refractory and relapsed or high risk malignant, who voluntarily received HSCT was analyzed. Among the 30 patients there were 4 relapsed cases and 26 cases of high risk malignant hematologic diseases. The above-mentioned patients included 15 AML, 9 ALL, 3 pro T lymphoblast lymphoma/leukemia, 1 spleen boundary zone lymphoma IVB, 1 NK/T lymphoma and 1 Burkitt lymphoma IVB. The results showed that the implantation was achieved in all 30 cases, among them 19 cases (63%) had aGVHD and 6 cases (20%) had III-IV aGVHD, 8 cases (32%) had cGVHD including 1 case of extensive and 7 cases of limited. Three cases relapsed at 300 days (128-455 d) after transplantation. 8 cases died, among them 1 case died of relapse, 2 cases died of IV aGVHD with relapse, 5 cases died of infection and organ failure. It is concluded, the efficacy of hi-HSCT combined with umbilical cord MSC for treatment of patients with refractory and relapsed or high risk malignant hematologic diseases is favorable.
Cord Blood Stem Cell Transplantation ; methods ; Female ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo compare the hemopoietic reconstitution, immune reconstitution, infection, incidence of graft-versus-host disease (GVHD) and clinical outcome between unrelated donor peripheral blood stem cell (PBSC) transplantation and bone marrow (BM) transplantation for leukemias.

METHODSThe clinical results of 21 leukemia patients receiving G-CSF mobilized PBSC graft from unrelated donors were compared with that of 32 patients receiving unrelated BM transplants.

RESULTSCompared with BM grafts, the PBSC graft contained significantly more nucleated cells (P = 0.000), and resulted in a significantly shorter time-to-neutrophil (12.43 +/- 3.67 vs 16.16 + 2.99 days) and platelet engraftment (14.67 +/- 6.19 vs 21.23 +/- 8.25 days), (P = 0.000 and 0.003, respectively). T cell reconstitution between the two groups differed little after transplantation. The incidences of early-stage infection (42.86% vs 53.13%), the probabilities of acute graft-versus-host disease (aGVHD) (61.90% vs 71.88%), the grades III to IV aGVHD (23.81% vs 15.63%), the chronic GVHD (47.06% vs 43.48%) and the probabilities of relapse (6.90% vs 12.50%) between PBSC and BM groups all has no statistical significance (NS). The 2-year disease free survival (DFS) rates of the two groups were (50.14 +/- 12.00) % and (59.81 +/- 8.99)%, respectively also have no NS.

CONCLUSIONG-CSF-mobilized unrelated donor PBSCs engraft more rapidly in the recipients as compared with conventional BM grafts. The T cell reconstitution, the incidence of infection, the incidence and severity of aGVHD and cGVHD, and the 2-year DFS rates between the two groups all have no significant differences.

Adolescent ; Adult ; Bone Marrow Transplantation ; methods ; Disease-Free Survival ; Female ; Humans ; Leukemia ; surgery ; Male ; Peripheral Blood Stem Cell Transplantation ; methods ; Tissue Donors ; Transplantation Conditioning ; Transplantation, Homologous ; Treatment Outcome

Chimeric antigen receptor (CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia (ALL). Measurable/minimal residual disease (MRD) monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy. Common MRD detection methods include flow cytometry (FCM), polymerase chain reaction (PCR), and next-generation sequencing (NGS), and each method has advantages and limitations. It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse. Thus, how to perform prognostic evaluations, stratify risk based on MRD status, and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice. This review assesses the common and novel MRD assessment methods. In addition, we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), as well as other therapeutic strategies to improve treatment effect. Furthermore, this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.
Humans ; Receptors, Chimeric Antigen/therapeutic use* ; Neoplasm, Residual ; Transplantation, Homologous/methods* ; Transplantation Conditioning/methods* ; Hematopoietic Stem Cell Transplantation/methods* ; Recurrence ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*

OBJECTIVETo explore the therapeutic feasibility of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from partially HLA-mismatched related donors for hematologic diseases.

METHODSThirty patients with hematologic diseases received allo-HSCT from 1 - 3 loci mismatched related donors conditioning regimen consisting of ATG (thymoglobulin, total dose of 10 mg/kg, intravenously on - 4 d to - 1 d), and only 5 (18%) of 28 recipients from HLA-identical sibling donors were treated with regimen containing ATG. Donors were given G-CSF prior to hematopoietic stem cell harvest and CsA, short-term MTX and mycophenolate mofetil (MMF) were used for GVHD prophylaxis in both group.

RESULTSAll patients were successfully engrafted. There was no significant difference in the incidence of grade II to IV acute graft-versus-host disease (aGVHD) and grade III to IV aGVHD between the mismatched and matched groups (34% vs 32%, and 13% vs 11%, respectively). 3-year overall survival (OS) and disease-free survival (DFS) in mismatched and matched groups were 57% vs 77% (P = 0.14) and 57% vs 69% (P = 0.28), respectively. Multivariate analysis showed that advanced disease pre-transplant (P = 0.006) and CMV infection (P = 0.04) were risk factors for OS. OS for patients with stable disease in mismatched and matched groups were 87% vs 81% (P = 0.65) respectively, and for those with advanced disease were 21% vs 71% (P = 0.02).

CONCLUSIONSIt is feasible to perform allo-HSCT from 1 -3 loci HLA-mismatched related donors for patients with stable disease who lack HLA-identical sibling donors. Nevertheless, for patients with advanced disease optimized conditioning regimen and intensive supporting therapy should be administered to obtain better clinical outcomes.

Graft vs Host Disease ; prevention & control ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Siblings ; Tissue Donors ; Transplantation Conditioning

Child ; Graft Survival ; HLA Antigens ; genetics ; immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Polymerase Chain Reaction ; Tissue Donors ; Transplantation Chimera ; genetics ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; immunology