Citations 3
Haploidentical Donor Blood or Marrow Transplantation for Myelodysplastic/Myeloproliferative Overlap Neoplasms: Results from a North American Collaboration
Jain, Tania , Tsai, Hua‐Ling , Elmariah, Hany , Vachhani, Pankit , Wall, Sarah , Gondek, Lukasz P. , Bashey, Asad, Keyzner, Alla , Tamari, Roni , Nadiminti, Kalyan , Ali, Haris , Jones, Richard J. , Gondek, Lukasz , Tamari, Roni , Grunwald, Michael , Gerds, Aaron T , McCurdy, Shannon , Al Malki, Monzr M , Ali, Haris , Gupta, Vikas , Jain, Tania , Elmariah, Hany , Karantanos, Theodoros , Grunwald, Michael R. , Abedin, Sameem , Iqbal, Madiha , Gerds, Aaron T. , Viswabandya, Auro , Malki, Monzr M. Al , Varadhan, Ravi , Gupta, Vikas , Otoukesh, Salman
No container title available | March 21, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
AbstractHaploidentical donors offer a potentially readily available donor, especially for non-White patients, for blood or marrow transplantation (BMT). In this collaboration across North America, we retrospectively analyzed outcomes of first BMT using haploidentical donor and posttransplantation cyclophosphamide (PTCy) in MDS/MPN-overlap neoplasms (MDS/MPN), an otherwise incurable hematological neoplasm. We included 120 patients, 38% of non-White/Caucasian ethnicity, across 15 centers with median age at BMT 62.5 years. The median follow-up is 2.4 years. Graft failure was reported in 6% patients. At 3-years, nonrelapse mortality (NRM) was 25%, relapse 27%, grade 3-4 acute graft versus host disease (GVHD) 12%, chronic GVHD requiring systemic immunosuppression 14%, progression-free survival (PFS) 48% and overall survival (OS) 56%. On multivariable analysis, statistically significant associations included older age at BMT (per decade increment) with NRM (sdHR 3.28, 95%CI 1.30-8.25), PFS (HR 1.98, 95% 1.13-3.45) and OS (HR 2.01, 95% CI 1.11-3.63), presence of mutation in EZH2/RUNX1/SETBP1 with relapse (sdHR 2.61, 95%CI 1.06-6.44), and splenomegaly at BMT/prior splenectomy with OS (HR 2.20, 95%CI 1.04-4.65). Haploidentical donors are a viable option for BMT in MDS/MPN, especially for those disproportionately represented in the unrelated donor registry. Disease-related factors including splenomegaly and high-risk mutations dominate outcomes following BMT.
Haploidentical Donor Transplantation with Posttransplantation Cyclophosphamide in Myelodysplastic/Myeloproliferative Neoplasms: A Multi-Institutional Collaboration of 14 Centers
Jain, Tania , Tsai, Hua‐Ling , Elmariah, Hany , Vachhani, Pankit , Wall, Sarah , Gondek, Lukasz P. , Bashey, Asad, Keyzner, Alla , Abedin, Sameem , Nadiminti, Kalyan VG, Malki, MHD Monzr M. Al, Ali, Haris , Jones, Richard J., Elmariah, Hany , Gondek, Lukasz , Abedin, Sameem , Karantanos, Theodoros , Grunwald, Michael R. , Iqbal, Madiha , Gerds, Aaron T. , Viswabandya, Auro , McCurdy, Shannon , Varadhan, Ravi , Gupta, Vikas , Otoukesh, Salman
Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 7731-7733
The diagnostic utility of targeted gene panel sequencing in discriminating etiologies of cytopenia
Zheng, Gang , Chen, Ping , Pallavajjalla, Aparna, Haley, Lisa , Gondek, Lukasz P. , Ling, Hua , Marchi, Federico De , Lin, Ming‐Tseh, Gocke, Christopher D. , De Marchi, Federico , Gondek, Lukasz , Dezern, Amy Elizabeth
American Journal of Hematology | July 27, 2019 | Volume: 94 | Issue: 10 | Pages: 1141-1148
Abstract The diagnostic utility of somatic mutations in the context of cytopenias is unclear: clonal hematopoiesis can be found in healthy individuals, patients with aplastic anemia (AA), clonal cytopenia of undetermined significance (CCUS) and myelodysplastic syndrome (MDS). We examined a cohort of 207 well‐characterized cytopenic patients with a 640‐gene next generation sequencing (NGS) panel and compared its diagnostic utility with a “virtual” 41 gene panel. The TET2 , SF3B1 , ASXL1 , and TP53 were the most commonly mutated genes (frequency > 10%). Mutations in the 640‐gene panel show high sensitivity (98.3%) but low specificity (47.6%) for diagnosis of MDS. Notably, mutations of splicing factors and genes in the RAS pathway are relatively specific to MDS. Furthermore, high variant allele frequency (VAF) predicts MDS: when the VAF is set at 20%, the positive predictive value (PPV) for MDS is 95.9%, with a specificity of 95.3%. The presence of two or more somatic mutations with ≥10% VAF showed a PPV of 95.2%. While the “virtual” 41‐gene panel showed a mild decrease in sensitivity (95.7% vs 98.3%), 100% specificity was observed when either VAF was set at ≥20% (100% vs 95.3%), or two or more somatic mutations had VAFs ≥ 10%. Our study shows targeted gene panel sequencing improves the diagnostic approach and accuracy for unexplained cytopenia, with its high sensitivity and high PPV for MDS when applying VAF cutoffs. Furthermore, a 41‐gene panel was shown to have at least comparable performance characteristics to the large 640‐gene panel.