Tacrolimus does not abrogate the increased risk of acute graft-versus-host disease after unrelated-donor marrow transplantation with allelic mismatching at HLA-DRB1 and HLA-DQB1

AbstractOne hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unrelated donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and minimethotrexate for prevention of acute graft-versus-host disease (GVHD). Sixty-eight patient-donor pairs had allelic matches at HLA-DRB1 and HLA-DQB1, 20 pairs had a single mismatch at HLA-DRB1 or HLA-DQB1, and 12 were mismatched at both HLA-DRB1 and HLA-DQB1. Minimum follow-up time was 6 months. Grades 2 to 4 GVHD occurred in 43% of patients with matched donors, 69% with single allele-mismatched donors, and 71% with double allele-mismatched donors; grades 3 to 4 GVHD occurred in 22%, 43%, and 64%, respectively. On multivariate analysis, the relative risk of grades 2 to 4 GVHD was 2.2 (95% CI, 1.1-4.5; P = .03) with a single allele mismatch and 2.7 (95% CI, 1.2-6.0; P = .02) with a double allele mismatch. The relative risks of grades 3 to 4 GVHD were 3.0 (95% CI, 1.2-7.6; P = .02) and 5.0 (95% CI, 1.9-12.6; P = .001), respectively. Day 100 treatment-related mortality was also adversely affected by allelic mismatching, occurring in 21% of those with matched donors, 50% with single allele-mismatched donors, and 42% with double allele-mismatched donors (P = .02), but overall survival at day 180 did not differ significantly among the 3 groups. Tacrolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.Biol Blood Marrow Transplant 2000;6(2A):190-7

Pharmacokinetics-directed Intravenous Busulfan Combined With High-dose Melphalan and Bortezomib as a Conditioning Regimen for Patients With Multiple Myeloma

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m PATIENTS AND METHODS: We conducted a prospective phase II study to investigate the safety and efficacy of conditioning with pharmacokinetics (PK)-directed intravenous (IV) Bu with Btz and Mel. Bu dosing was adjusted to target a total area under the curve (AUC) of 20,000 μM × min. Patients received Btz (1 mg/m RESULTS: A total of 19 subjects were enrolled. Their median age was 55 years, and the median follow-up period was 23.7 months. PK testing resulted in 86% of patients achieving an estimated total AUC of 20,000 ± 2500 μM × min. The overall response rate (ORR) at day +100 after ASCT was 100% in the evaluable patients, with 11% of patients achieving a complete response. The 2-year progression-free survival rate was 57.9% (95% confidence interval [CI], 38%-89%), and the 2-year overall survival rate was 88.5% (95% CI, 76%-100%). The most common grade 3 and 4 toxicities were febrile neutropenia, dysphagia/odynophagia, and oral mucositis. No case of hepatic sinusoidal obstruction syndrome developed. One treatment-related mortality occurred before day +100. CONCLUSION: A preparative regimen of PK-directed IV Bu with Btz and Mel led to an ORR of 100% with acceptable toxicity and should be considered for direct comparison with the Mel200 regimen in future trials

Ibrutinib‐induced severe liver injury

Ibrutinib, an inhibitor of the Bruton's tyrosine kinase of the B‐cell receptor pathway, is an effective therapeutic agent for B‐cell lymphomas. As these drugs are novel, long‐term or rare adverse events are not yet known. We report the first case of ibrutinib‐induced severe liver injury in a patient with relapsed/refractory CLL

Case report of combination therapy with Azacytidine, Enasidenib and Venetoclax in primary refractory AML.

Optimal treatment of acute myeloid leukemia (AML) arising in elderly patients remains a challenge. FDA approval of Ivosidenib and Enasidenib, small molecule inhibitors of isocitrate dehydrogenase enzymes (IDH1 and 2) have opened new avenues of treatment. We present a 60-year-old woman with refractory AML, achieving complete response to the combination therapy of hypomethylating agent, Azacytidine with the IDH2 inhibitor, Enasidenib, and BCL2 inhibitor, Venetoclax. To our knowledge, this is the first case report of a patient with IDH2 mutated refractory AML achieving complete response to combination therapy with azacytidine, enasidenib and venetoclax