Predictive Factors of Survival Time after Hematopoietic Stem Cell Transplant in Acute Myeloid Leukemia Patients who Received Allogeneic BMT from Matched Sibling Donors Using Generalized Gamma Models


Introduction: This paper used Generalized Gamma (GG) distribution to find the predictive factors of overall survival (OS) after haematopoietic stem cell transplant (HSCT) in acute myeloid  leukemia patients.
Methods: Discrimination among the exponential, Weibull, GG, log-logistic, and lognormal distributions was done using maximum likelihood and Akaike information criteria.
Results: The 5-year OS in 301 patients was 65% (95%CI: 60.7-69.3). Peak mortality hazard occurred at months 6-7 after HSCT then, it was U Shape. The data was fitted by GG distribution better than other distributions. Univariate analysis using GG distribution showed a positive association between OS with dose of infused WBC (P=0.018), CD3 (p=0.001), no relapse (P<0.001), cGVHD (P<0.001), and platelet recovery (P<0.001). Multivariate analysis indicated that, OS has relationship with relapse (P<0.001), platelet recovery (P=0.004), disease status at transplant (P=0.036) and aGVHD (P=0.036).
Conclusion: We showed that GG distribution can be a useful tool for recognizing prognostic factors of OS in AML patients.

Avivi I, Rowe JM. Prognostic factors in acute myeloid leukemia. Curr Opin Hematol. 2005;12:62-67.

Lowenberg B, Downning JR, Burnett A. Acute myeloid leukemia. N Engl J Med 1999; 341:1051-1062.

Alamo JG, Shahjahan M, Wong RS, et al. Prognostic factors for allogeneic stem cell transplantation (ASCT) for untreated first relapse of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Biol Blood Mrrow Transplant. 2005 ;11:38-39.

Mayer RJ, Davis RB, Shiffer CA, et al. Intensive post remission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994;331:896-903.

Reddy V, Winer AG, Eksioglu E, et al. Interleukin 12 is associated with reduced relapse without increased incidence of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005;11:1014-1021.

Kadan-Lottick NS, Ness KK, Bhatia S, Gurney JG. Survival variability by race and ethnicity in childhood acute lymphoblastic leukemia. JAMA. 2003;290:2061-2063.

Hotowiecki J, Wojnar J, Krawczyk-Kuliś M, et al. Allogeneic and autologous bone marrow transplantation in single centre experience. Bone Marrow Transplant. 1998;22:100-103.

Blum W, Bolwell BJ, Phillips G, et al. High disease burden is associated with poor outcomes for patients with acute myeloid leukemia not in remission who undergo unrelated donor cell transplantation. Biol Blood Marrow Transplant. 2006 Jan;12(1):61-67.

Kim DH, Won DI, Lee NY, et al. Non-CD34+ cells, especially CD8+ cytotoxic T cells and CD56+ natural killer cells, rather than CD34 cells, predict early engraftment and better transplantation outcomes in patients with hematologicmalignancies after allogeneic peripheral stem cell transplantation. Biol Blood Mrrow Transplant. 2006;12:719- 728.

Orbe J, Ferreira E, Núñez-Antón V. Comparing proportional hazards and accelerated failure time models for survival analysis. Stat Med. 2002;21(22):3493-3510.

Cox C, Chu H, Schneider MF, Muñoz A. Parametric survival analysis and taxonomy of hazard functions for the generalized gamma distribution. Stat Med. 2007;26(23):4352- 4374.

Sayehmiri K, Eshraghian MR, Mohammad K, et al. Prognostic factors of survival time after hematopoietic stem cell transplant in acute lymphoblastic leukemia patients: Cox proportional hazard versus accelerated failure time models. J Exp Clin Cancer Res. 2008;27:74.

Kleinbaum DG, Klein M. Survival Analysis -A Self- Learning Text. 2nd ed. New York: Springer –Verlag; 2005.

Steiner S, Winkelmayer WC, Kleinert J, et al. Endothelial progenitor cells in kidney transplant recipients. Transplantation. 2006;81:599-606.

Saint-Marcoux F, Knoop C, Debord J, et al. Pharmacokinetic study of tacrolimus in cystic fibrosis and non-cystic fibrosis lung transplant patients and design of Bayesian estimators using limited sampling strategies. Clin Pharmacokinet. 2005;44:1317-1328.

Winkelmayer WC, Huber A, Wagner OF, et al. Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B in kidney transplant recipients. Kidney Int. 2005;67:1980-1985.

Winkelmayer WC, Eberle C, Sunder-Plassmann G, Födinger M. Effects of the glutamate carboxypeptidase II (GCP2 1561C>T) and reduced folate carrier (RFC1 80G>A) allelic variants on folate and total homocysteine levels in kidney transplant patients. Kidney Int. 2003;63:2280-2285.

Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation. 1974;18:295-304.

Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graftversus-host syndrome in man (a long-term clinicopathologic study of 20 Seattle patients). Am J Med. 1980;69:204–217.

Nannya Y, Kanda Y, Oshima K, et al. Prognostic factors in elderly patients with acute myelogenous leukemia: a single center study in Japan. Leuk Lymphoma. 2002;43:83-87

Johnson PR, Hunt LP, Yin JA. Prognostic factors in elderly patients with acute myeloid leukaemia: development of a model to predict survival. Br J Haematol. 1993; 85:300- 306.

Klien JP, Moeschberger M. Survival analysis techniques for censored and truncated data. Springer –Verlag; 1997.

Allison PD. Survival Analysis using the sas system a practical guide. SaS Institutes; 1995.

Shao XM. Parametric survival analysis for gating kinetics of single potassium channels. Brain Res. 1997;770:96-104

Verstovsek S, Estey E, Manshouri T, et al. Clinical relevance of vascular endothelial growth factor receptors 1 and 2 in acute myeloid leukaemia and myelodysplastic syndrome. Br J Haematol. 2002;118:151-156.

Sakamoto S, Kurata H, Miwa A. Multivariate analysis of prognostic factors influencing survival in chronic myelogenous leukemia. Rinsho Ketsueki. 1989;30:1180-1184.

Kolb E Anders, Pooja Gidwani, Stephan A Grupp, Hematopoietic Stem Cell Transplantation. eMedicine Specialties 2006; Pediatrics: General Medicine, Oncology.

Barrett AJ, Horowitz MM, Gale RP, et al. Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival. Blood. 1989;74:862-871.

Vernant JP, Marit G, Maraninchi D, et al. Allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia in first complete remission. J Clin Oncol. 1988;6:227-231.

Blaise D, Gaspard MH, Stoppa AM, et al. Allogeneic or autologous bone marrow transplantation for acute lymphoblastic leukemia in first complete remission. Bone Marrow Transplant. 1990;5:7-12.

Wingard JR, Piantadosi S, Santos GW, et al. Allogeneic bone marrow transplantation for patients with high-risk acute lymphoblastic leukemia J Clin Oncol. 1990;8(5):820-830.

Wahlin A, Markevärn B, Golovleva I, Nilsson M. Improved outcome in adult acute myeloid leukemia is almost entirely restricted to young patients and associated with stem cell transplantation. Eur J Haematol. 2002;68:54-63.

Brincker H, Christensen B E. Long-term survival and late relapses in acute leukaemia in adults. Br J Haematol. 1990;74:156-160.

Fung HC, Stein A, Slovak M, et al. A long-term follow- up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome. Biol Blood Marrow Transplant. 2003;9:766-771.

Grigg AP, Gibson J, Bardy PG, et al. A prospective multicenter trial of peripheral blood stem cell sibling allografts for acute myeloid leukemia in first complete remission using fludarabine-cyclophosphamide reduced intensity conditioning. Biol Blood Marrow Transplant. 2007;13:560-567.

Zecca M, Prete A, Rondelli R, et al. Chronic graft-versus- host disease in children: incidence, risk factors, and impact on outcome. Blood. 2002;100(4):1192-1200.

Doney K, Hägglund H, Leisenring W, et al. Predictive factors for outcome of allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2003;9:472-481.

Jagasia M, Giglia J, Chinratanalab W, et al. Incidence and outcome of chronic graft-versus-host disease using National Institutes of Health consensus criteria. Biol Blood Marrow Transplant. 2007;13:1207-1215.

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acute myeloid leukaemia prognostic factors generalized gamma distribution survival analysis

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Sayemiri K, Eshraghian M, Mohammad K, Alimoghaddam K, Rahimi Foroushani A, Zeraati H, Shamshiri AR, Djafarian K, Ghavamzadeh A. Predictive Factors of Survival Time after Hematopoietic Stem Cell Transplant in Acute Myeloid Leukemia Patients who Received Allogeneic BMT from Matched Sibling Donors Using Generalized Gamma Models. Int J Hematol Oncol Stem Cell Res. 1;3(1):21-26.