Browsing by Author "Gadalla, Shahinaz M"

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    Outcomes of allogeneic hematopoietic cell transplantation in patients with dyskeratosis congenita.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2013-08) Gadalla, Shahinaz M; Sales-Bonfim, Carmem; Carreras, Jeanette; Alter, Blanche P; Antin, Joseph H; Ayas, Mouhab; Bodhi, Prasad; Davis, Jeffrey; Davies, Stella M; Deconinck, Eric; Deeg, H Joachim; Duerst, Reggie E; Fasth, Anders; Ghavamzadeh, Ardeshir; Giri, Neelam; Goldman, Frederick D; Kolb, E Anders; Krance, Robert; Kurtzberg, Joanne; Leung, Wing H; Srivastava, Alok; Or, Reuven; Richman, Carol M; Rosenberg, Philip S; Toledo Codina, Jose Sanchez de; Shenoy, Shalini; Socié, Gerard; Tolar, Jakub; Williams, Kirsten M; Eapen, Mary; Savage, Sharon A
    We describe outcomes after allogeneic transplantation in 34 patients with dyskeratosis congenita who underwent transplantation between 1981 and 2009. The median age at transplantation was 13 years (range, 2 to 35). Approximately 50% of transplantations were from related donors. Bone marrow was the predominant source of stem cells (24 of 34). The day-28 probability of neutrophil recovery was 73% and the day-100 platelet recovery was 72%. The day-100 probability of grade II to IV acute GVHD and the 3-year probability of chronic graft-versus-host disease were 24% and 37%, respectively. The 10-year probability of survival was 30%; 14 patients were alive at last follow-up. Ten deaths occurred within 4 months from transplantation because of graft failure (n = 6) or other transplantation-related complications; 9 of these patients had undergone transplantation from mismatched related or from unrelated donors. Another 10 deaths occurred after 4 months; 6 of them occurred more than 5 years after transplantation, and 4 of these were attributed to pulmonary failure. Transplantation regimen intensity and transplantations from mismatched related or unrelated donors were associated with early mortality. Transplantation of grafts from HLA-matched siblings with cyclophosphamide-containing nonradiation regimens was associated with early low toxicity. Late mortality was attributed mainly to pulmonary complications and likely related to the underlying disease.
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    Survival following allogeneic transplant in patients with myelofibrosis.
    (Blood advances, 2020-05) Gowin, Krisstina; Ballen, Karen; Ahn, Kwang Woo; Hu, Zhen-Huan; Ali, Haris; Arcasoy, Murat O; Devlin, Rebecca; Coakley, Maria; Gerds, Aaron T; Green, Michael; Gupta, Vikas; Hobbs, Gabriela; Jain, Tania; Kandarpa, Malathi; Komrokji, Rami; Kuykendall, Andrew T; Luber, Kierstin; Masarova, Lucia; Michaelis, Laura C; Patches, Sarah; Pariser, Ashley C; Rampal, Raajit; Stein, Brady; Talpaz, Moshe; Verstovsek, Srdan; Wadleigh, Martha; Agrawal, Vaibhav; Aljurf, Mahmoud; Angel Diaz, Miguel; Avalos, Belinda R; Bacher, Ulrike; Bashey, Asad; Beitinjaneh, Amer M; Cerny, Jan; Chhabra, Saurabh; Copelan, Edward; Cutler, Corey S; DeFilipp, Zachariah; Gadalla, Shahinaz M; Ganguly, Siddhartha; Grunwald, Michael R; Hashmi, Shahrukh K; Kharfan-Dabaja, Mohamed A; Kindwall-Keller, Tamila; Kröger, Nicolaus; Lazarus, Hillard M; Liesveld, Jane L; Litzow, Mark R; Marks, David I; Nathan, Sunita; Nishihori, Taiga; Olsson, Richard F; Pawarode, Attaphol; Rowe, Jacob M; Savani, Bipin N; Savoie, Mary Lynn; Seo, Sachiko; Solh, Melhem; Tamari, Roni; Verdonck, Leo F; Yared, Jean A; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Scott, Bart L; Nakamura, Ryotaro; Mesa, Ruben; Saber, Wael
    Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.
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    Telomeres and the natural lifespan limit in humans.
    (Aging (Albany NY), 2017-04) Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon; Thinggaard, Mikael; Hjelmborg, Jacob VB; Dalgård, Christine; Kyvik, Kirsten Ohm; Christiansen, Lene; Mangino, Massimo; Spector, Timothy D; Petersen, Inge; Kimura, Masayuki; Benetos, Athanase; Labat, Carlos; Sinnreich, Ronit; Hwang, Shih-Jen; Levy, Daniel; Hunt, Steven C; Fitzpatrick, Annette L; Chen, Wei; Berenson, Gerald S; Barbieri, Michelangela; Paolisso, Giuseppe; Gadalla, Shahinaz M; Savage, Sharon A; Christensen, Kaare; Yashin, Anatoliy I; Arbeev, Konstantin G; Aviv, Abraham
    An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends in life expectancy should confront a biological limit due to crossing the telomeric brink.