Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
Treatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKIs) with or without donor lymphocyte infusions (DLIs), but the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002 to 2014 who underwent HCT for CML and were alive 30 days postrelapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups: (1) TKI alone (n = 128), (2) TKI with DLI (n = 48), and (3) DLI without TKI (n = 39). In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients who received a DLI alone compared with a TKI with a DLI had inferior survival (hazard ratio, 2.28; 95% confidence interval, 1.23 to 4.24; P= .009). Those who received a TKI alone had similar survival compared with those who received a TKI with a DLI (P = .81). These data support that despite use of TKIs pretransplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data do not suggest that adding a DLI to a TKI adds an improvement in OS.
International Journal of Medicine and Public Health,2011,1,4,28-38.DOI:10.5530/ijmedph.4.2011.7Published:Oct/2011Type:Original ArticleClinical Profile and outcome of envenomous snake-bite at tertiary care centre in western MaharashtraVirendra C. patil, Harsha V. Patil, Avinash Patil, and Vaibhav Agrawal Virendra C. Patil1, Harsha V. Patil2, Avinash Patil1, Vaibhav Agrawal1 1Department of Medicine , Krishna Institute of Medical Sciences University, Dhebewadi Road, Karad, Satara District, Maharashtra – 415 110, India. 2Department of Microbiology , Krishna Institute of Medical Sciences University, Dhebewadi Road, Karad, Satara District, Maharashtra – 415 110, India. Abstract:Background: Venomous snake bite is a common and frequently devastating environmental and occupational disease, especially in rural areas of Maharashtra India. Aims and Objectives: To determine the clinical profile and outcome of snakebite cases in rural western Maharashtra. Material and Methods: This was a retrospective study conducted over one year period (January 2009 to December 2009) at a tertiary health care centre in Maharashtra. Results: Out of 167 admitted snakebite 103 (61.67%) were complicated snake bites. Total 88 (85.43%) patients were with vasculo-toxic snake bite. Total 15 (14.56%) patients were with neuroparalytic snakebite. Total 35 (39.77%) patients out of 88 with vasculotoxic snakebite developed local cellulitis requiring fasciotomy and or debridement, 17 (19.31%) patients had clinical and laboratory parameters favoring DIC. Total 12 (13.63%) patients had ARF, one developed AMI and one developed cortical venous sinus thrombosis (CVT). Out of 88 patients with vasculotoxic snakebite 2 died with case fatality rate of 2.27% (2/88). Out of 15 patients with neuroparalytic snake bite 13 (86.66%) required artificial ventilatory support and one patient developed delayed peripheral neuropathy. Overall mortality was 1.94% (2/103). The needle to ASV time was positively correlated with duration of hospital admission, complications and mortality (‘p’ < 0.02). Conclusion: Snakebite is a common life-threatening emergency in the study area. Delay in hospitalization is associated with poor prognosis and increased mortality rate due to consumptive coagulopathy, renal failure and respiratory failure. Unusual complications like AMI, CVT and delayed peripheral neuropathy were observed in present study. Keywords:AMI, ARF, ASV., Complicated snake bites, DICView:PDF (731.07 KB)
The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which have historically had limited responses. Combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker) has had limited discussion in the literature.
Abstract There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
Abstract Purpose Over the past decade, drug shortages have become increasingly more problematic for clinicians, with over 300 drug shortages reported in the first quarter of 2023. Shortages of chemotherapy drugs can have a negative impact on patient care, as omission or delay of treatment can lead to worse outcomes. Although many articles have been published on this topic, currently no review articles discuss strategies for using alternative regimens or substitutions in the event of severe chemotherapy drug shortages. Summary In this article, we review the literature on antineoplastic agents used to treat hematologic malignancies that experienced a drug shortage from 2010 through 2023, providing recommendations for substitutions and alternative regimens in the event of a critical shortage. In particular, we discuss how shortages of fludarabine, cytarabine, daunorubicin, methotrexate, and platinum agents may be addressed, including supporting clinical evidence. Conclusion Further publications assessing possible alternatives and substitutions for chemotherapy agents and examining the efficacy of previous strategies are needed to mitigate potentially devastating interruptions to care for patients with cancer during severe drug shortages.
