2008, Number 6
Rev Invest Clin 2008; 60 (6)
Acute limphoblastic leukemia: experience in adults patients treated with hyperCVAD and 0195 Protocol, at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Cohort 2003-2007
Arteaga-Ortiz L, Buitrón-Santiago N, Rosas-López A, Rosas-Arzate G, Armengolt-Jiménez A, Aguayo Á, López-Karpovitch X, Crespo-Solís E
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Despite therapeutic advances, acute lymphoblastic leukemia (ALL) in adults remains a disease with poor long term outcome and survival rates. Developing countries lack of information about this disease. On the other hand, infections are frequent complications related to mortality and some research studies do not show accurate rates of septic shock or other related factors. Objective.
To describe characteristics of adults with acute lymphoblastic leukemia, response to treatment, complications and to evaluate further survival related factors and to compare our experience with other reports of literature. Material and methods.
Between September 2003 to November 2007, the entire cohort of patients with diagnosis of ALL was included. The treatment regimens used were MDACC HyperCVAD (HCVAD) and 0195 (institutional regimen). Results.
Of 40 patients included with the diagnosis of ALL, 92% was B phenotype and 8%, T phenotype, with a median age of 27 years. The median follow up was 28.5 months. Initially, 14% showed central nervous system infiltration; of 51% with available cytogenetics, 16.7% was Philadelphia chromosome positive. There were 36 patients who received treatment: 13 received HCVAD and 23 the 0195 protocol; 78% achieved global complete remission, 85% for the patients with HCVAD and 74% with 0195. The induction death rate was 2.8%. The median disease-free survival was 11.6 months (IC 95%, 2.5-20.8 months) and overall survival was 15 months (IC 95%, 10.6-19.4 months). In 95% of patients, no prophylactic antibiotic therapy was used and treatment related death was 8.4% (2.8% during induction and 5.6% during the rest of treatment). Factors associated with worse survival rate were hyperleukocytosis, T phenotype and lack of early complete remission. During induction, grade 3 to 4 non hematopoietic toxicity was 17%. Incidence of neutropenic febrile episodes was 61% and septic shock was 11%. Conclusions.
With HCVAD, we observed worse complete remission, disease-free survival and overall survival rates compared with the original MDACC reports. Chemotherapy related death rates are similar to other early reports, despite prophylactic antibiotic was not used during myelosupression.
Kantarjian H, Thomas D, O’Brien S, Cortes J, Giles F, Sima J, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper- CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 2004; 101: 2788-801.
Goldstone A, Richards S, Lazarus H, Tallman MS, Buck G, Rowe JM, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of International ALL Trial (MRC UKALLXII/ECOG E2993). Blood 2008; 111: 1827-33.
Bajel A, George B, Mathews V, Viswabandya A, Kavitha M, Chandy M, et al. Adul ALL: treatment outcome and prognostic factors in an Indian population using a modified German ALL (GMALL) protocol. Leukemia 2007; 21: 2230-3.
Avilés A, Ambriz R, Díaz JC, Mascaro J, Sinco A, Pizzuto J. Resultados de dos esquemas de quimioterapia (VPA y C-VPA) en la leucemia aguda linfoblástica del adulto. Rev Invest Clin 1983; 35: 285-9.
Sobrevilla P, Acosta A, López X, Salles, MT, Reynoso E, Guarner L J. Respuesta al tratamiento y supervivencia de adultos con leucemia aguda clasificadas mediante inmunofenotipo y citoquímica. Rev Invest Clin 1994; 46: 399-406.
Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Fiere D, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004; 22: 4075-86.
Jaffe E, Stein H, Vardiman JW. WHO: Classification of Tumours. Tumours of haematopoietic and lymhoid tissue. Lyon: IARC Press; 2001.
Annino L, Vegna ML, Camera A, Specchia G, Visani G, Mandelli F, et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood 2002; 99: 863-71.
Hoelzer D, Thiel E, Loffler H, Bodenstein H, Plaumann L, Engelhardt R, et al. Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults. Blood 1984; 64: 38-47.
Cheson BD, Cassilth PA, Head DR, Schiffer CA, Bennet JM, Bloomfield CD, et al. Report of the National Cancer Institutesponsored workshop on definitions of diagnosis and response in acute leukemia. J Clin Oncol 1990; 8: 813-19.
Specchia G, Pastore D, Carluccio P, Liso A, Mestice A, Liso V, et al. FLAG-IDA in the treatment of refractory/relapsed adult acute lymphoblastic leukemia. Ann Hematol 2005; 84: 792-5.
Hoelzer D, Thiel E, Loffler H, Buchner T, Ganser A, Ruhl H, et al. Prognostic factors in a multicenter study for treatment of acute lymphoblastic leucemia in adults. Blood 1988; 71: 123- 31.
Pui CH, Evans W, Treatment acute lymphoblastic leucemia: N Engl J Med 2006; 354: 166-78.
Ruiz-Argüelles GJ, Marin A, Ruiz A, Valls M, Perez B, Ruiz DS. Estudio prospectivo de la clasificación inmunológica en la ciudad de Puebla, México. Rev Invest Clin 1987; 39: 137-42.
Rego EM, García AB, Viana SR, Falcao RP. Characterization of acute lymphoblastic leucemia subtypes in brazilian patients. Leucemia Research 1996; 20: 349-55.
Larson RA. The US trials in adult acute lymphoblastic leukemia. Ann Hematol 2004; (83 Suppl. 1): S127-S128.
Ruiz-Argüelles GJ, Ruiz A, Aguilar E. Citometría de flujo en la inmunotipificación de las leucemias agudas (carta). Rev Invest Clin 1993; 45: 93.
Piedras J, López X, Cardenas MR. Inmunofenotipos celulares en 97 adultos con leukemia aguda. Rev Invest Clin 1997; 49: 457-64.
Piedras J, Barrales O, López X. Clasificación de las leucemias agudas de acuerdo con el consenso de la primera conferencia latinoamericana en la tipificación inmunológica de las leucemias. Rev Invest Clin 2000; 52: 524-8.
Gokbuget N, Hoelzer D, Arnold R, Bohme A, Bartram CR, Thiel E, et al. Treatment of adult ALL according to the protocols of the German Multicenter Study Group for Adult ALL (GMALL). Hematol Oncol Clin North Am 2000; 14: 1307-25.
Ruiz-Argüelles GJ, Marín-López A, Ruiz-Argüelles A. Immunologic classification of the acute non-granular leucemias in the City of Puebla, México: its value in the diagnosis and prognosis. Rev Invest Clin 1987; 39: 143-7.
Uckun FM, Sather HN, Gaynon PS, Arthur DC, Trigg ME, Reaman GH, et al. Clinical features and treatment outcome of children with myeloid antigen positive acute lymphoblastic leukemia: A report from the Children’s Cancer Group. Blood 1997; 90: 28-35.
Putti MC, Rondelli R, Cocito MG, Aricó M, Sainati L, Basso G, et al. Expression of myeloid markers lacks prognostic impact in children treated for acute lymphoblastic leukemia: Italian experience in AIEOP-ALL 88-91 studies. Blood 1998; 9: 795-801.
Ugarte A, Villasis A, Hernández ME, Crespo E, Ruiz GM, Ponce- De-León, et al. Utilidad de la profilaxis con fluoroquinolonas durante la neutropenia grave inducida por quimioterapia en pacientes con leucemia aguda, en un hospital de referencia de la ciudad de México con alta prevalencia de resistencia a fluoroquinolonas. Rev Invest Clin 2006; 58: 547-54.