Allogeneic hematopoeitic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF). We evaluate the impact of various factors on survival outcomes post-transplant in MF. Data of 89 consecutive MF patients (primary 47%) who underwent allo-HCT between 2005 and 2018 was evaluated. Fifty-four percent patients had received JAK1/2 inhibitors (JAKi) pre-HCT. The median CD34 count was 7.1x10 cells/kg. Graft failure was seen in 10% of the patients. Grade 3-4 acute GVHD (aGVHD) and moderate/severe chronic graft versus host disease (cGVHD) occurred in 24% and 40% patients, respectively. Two-year overall survival (OS) and relapse free survival (RFS) were 51% and 43%, respectively. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 2 years were 11% and 46%, respectively. Higher CD34 cell dose (≤5 × 10 cells/kg vs 5-9 or ≥9 × 10 cells/kg) and lower pre-HCT ferritin (=1000 ng/ml) were associated with better OS, RFS and lower NRM. Grade 3-4 aGVHD was associated with higher NRM. Use of pre-transplant JAKi was associated with lower incidence of grade 3-4 aGVHD. In summary, higher CD34 cell dose is associated with better allo-HCT outcomes in MF and pre-HCT JAKi use is associated with reduced risk of severe aGVHD. These two modifiable parameters should be considered during allo-HCT for MF.
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http://dx.doi.org/10.1111/ejh.13689 | DOI Listing |
Intern Med
January 2025
Department of Internal Medicine 1, Shimane University Faculty of Medicine, Japan.
We herein report a 56-year-old man with severe hypocalcemia during ruxolitinib therapy for myelofibrosis transitioning from JAK2 mutation-positive polycythemia vera. Blood transfusions were administered every one to two weeks for ruxolitinib-induced anemia. Blood tests revealed hypocalcemia with low TRACP-5b, 25-hydroxyvitamin D (25 (OH) D), and 1,25-dihydroxyvitamin D (1,25 (OH) D) levels within the lower reference range.
View Article and Find Full Text PDFSci Transl Med
January 2025
Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Familial platelet disorder (FPD) is associated with germline mutations, establishing a preleukemic state and increasing the risk of developing leukemia. Currently, there are no intervention strategies to prevent leukemia progression. Single-cell RNA sequencing ( = 10) combined with functional analysis of samples from patients with -FPD ( > 75) revealed that FPD hematopoietic stem and progenitor cells (HSPCs) displayed increased myeloid differentiation and suppressed megakaryopoiesis because of increased activation of prosurvival and inflammatory pathways.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary; Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen 4032, Hungary; Dean's office, Faculty of Pharmacy, University of Debrecen, Debrecen 4032, Hungary. Electronic address:
ABCB1/MDR-1/P-glycoprotein (Pgp) is an ABC transporter responsible for cancer cell multi-drug resistance. It is expressed in cytotoxic T lymphocytes (CTL). Eliminating sensitive cancer cells during high-dose chemotherapy can also damage immune cells.
View Article and Find Full Text PDFClin Cosmet Investig Dermatol
December 2024
Department of Dermatology, Air Force Medical Center, PLA, Beijing, People's Republic of China.
Background: Vitiligo is a chronic autoimmune disease manifested by depigmented patches of skin devoid of melanocytes. Baricitinib, a JAK inhibitor selectively targeting JAK1/2, has shown preliminary efficacy for vitiligo. We aimed to assess the efficacy and tolerability of combination therapy with baricitinib and narrowband UV-B (NB-UVB) to treat active nonsegmental vitiligo (NSV).
View Article and Find Full Text PDFClin Pharmacol Ther
December 2024
Clinical Trial Institution, Peking University People's Hospital, Beijing, China.
Although several case reports and small clinical trials have reported promising outcomes with Janus kinase (JAK) inhibitors for vitiligo, high-quality evidence and guidelines are lacking. We evaluated the efficacy and safety of JAK inhibitors for the treatment of vitiligo using a meta-analysis of randomized controlled trials (RCTs). We searched the PubMed, Embase, and Cochrane Library databases up to August 2023, with additional studies from ClinicalTrials.
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