311 research outputs found
Somatic CLL mutations occur at multiple distinct hematopoietic maturation stages: documentation and cautionary note regarding cell fraction purity
Baseline Thymopoietic Function and Post-Transplant Immune Recovery after Adult Cord Blood Transplantation
Reduced Intensity Conditioning (RIC) Regimen Followed By Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Adult Patients (PTS) With Acute Lymphoblastic Leukemia (ALL)
Evidence for B cell exhaustion in chronic graft-versus-host disease
Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21â B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21â B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively; p < 0.01). Compared with naĂŻve (CD27âCD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21â B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21â B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21â B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21âCD27âCD10â B cell frequencies as a biomarker of disease severity
8: Factors Affecting 100-Day and 1-Year Mortality Following Myeloablative Single-Unit Cord Blood Transplantation in Adults and Adolescents: A Comprehensive Meta-Analysis of CIBMTR, NCBP and Eurocord
Clofarabine ± Fludarabine with Once Daily i.v. Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and MDS
Although a combination of i.v. busulfan (Bu) and fludarabine (Flu) is a safe, reduced-toxicity conditioning program for acute myelogenous leukemia/myelodysplastic syndromes (AML/MDS), recurrent leukemia posttransplantation remains a problem. To enhance the conditioning regimenâs antileukemic effect, we decided to supplant Flu with clofarabine (Clo), and assayed the interactions of these nucleoside analogs alone and in combination with Bu in Bu-resistant human cell lines in vitro. We found pronounced synergy between each nucleoside and the alkylator but even more enhanced cytotoxic synergy when the nucleoside analogs were combined prior to exposing the cells to Bu. We then designed a 4-arm clinical trial in patients with myeloid leukemia undergoing allogeneic stem cell transplantation (allo-SCT). Patients were adaptively randomized as follows: Arm IâClo:Flu 10:30 mg/m2, Arm IIâ20:20 mg/m2, Arm IIIâ30:10 mg/m2, and Arm IVâsingle-agent Clo at 40 mg/m2. The nucleoside analog(s) were/was infused over 1 hour once daily for 4 days, followed on each day by Bu, infused over 3 hours to a pharmacokinetically targeted daily area under the curve (AUC) of 6000 ÎŒMol-min ± 10%. Fifty-one patients have been enrolled with a minimum follow-up exceeding 100 days. There were 32 males and 19 females, with a median age of 45 years (range: 6-59). Nine patients had chronic myeloid leukemia (CML) (BC: 2, second AP: 3, and tyrosine-kinase inhibitor refractory first chronic phase [CP]: 4). Forty-two patients had AML: 14 were induction failures, 8 in first chemotherapy-refractory relapse, 7 in untreated relapse, 3 in second or subsequent relapse, 4 were in second complete remission (CR), and 3 in second CR without platelet recovery (CRp), 2 were in high-risk CR1. Finally, 1 patient was in first CRp. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus and mini-methorexate (MTX), and those who had an unrelated or 1 antigen-mismatched donor received low-dose rabbit-ATG (Thymoglobulinâą). All patients engrafted. Forty-one patients had active leukemia at the time of transplant, and 35 achieved CR (85%). Twenty of the 42 AML patients and 5 of 9 CML patients are alive with a projected median overall survival (OS) of 23 months. Marrow and blood (T cell) chimerism studies at day +100 revealed that both in the lower-dose Clo groups (groups 1+2) and the higher-dose Clo groups (groups 3+4), the patients had a median of 100% donor (T cell)-derived DNA. There has been no secondary graft failure. In the first 100 days, 1 patient died of pneumonia, and 1 of liver GVHD. We conclude that (1) Clo ± Flu with i.v. Bu as pretransplant conditioning is safe in high-risk myeloid leukemia patients; (2) clofarabine is sufficiently immunosuppressive to support allo-SCT in myeloid leukemia; and (3) the median OS of 23 months in this high-risk patient population is encouraging. Additional studies to evaluate the antileukemic efficacy of Clo ± Flu with i.v. Bu as pretransplant conditioning therapy are warranted
Impact of the timing of hepatitis B virus identification and antiĂą hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138209/1/cncr30729_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138209/2/cncr30729.pd
2: Donor-Recipient Host-Versus-Graft Human Leukocyte Antigen Mismatches and Outcome of Cord Blood Transplants
Digitalitzat per Artypla
2: Donor-Recipient Host-Versus-Graft Human Leukocyte Antigen Mismatches and Outcome of Cord Blood Transplants
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