[Analysis of clinical-biological features of adult acute lymphoblastic leukemia]. / Análisis de características clinicobiológicas de leucemia aguda linfoblástica del adulto.

INTRODUCCTION: Acute lymphoblastic leukemia (ALL) is a clonal disease characterized by a proliferation of immature cells. In immunophenotypic, cytogenetic and molecular studies, it is a heterogeneous disease with diverse manifestations and prognoses. The treatment is complex and is associated with complications during its course. PATIENTS AND METHODS: A prospective study of cohort of patients with ALL. Subjects were recruited consecutively from April 2010 to November 2012 in the Specialties Hospital, /MSS. RESULTS: We included 29 patients with ALL; of 16 females (55%) and 13 males (45%), 18 (64%) were treated with modified BFM, seven (25%) HiperCVAD, and three (11 %) others. In all, 70% achieved complete remission, and 8.5% partial responses. Induction mortality in five patients (17%). Consolidation mortality in three (13%). Relapse 33%, with a mean of eight months (5- 16 months), overall survival five months. At 26 months of follow-up, 13 patients (45%) maintained RC. Disease-free survival of 10 months and overall survival of 12 months was observed. CONCLUSION: The majority of patients, regardless of risk, reach complete remission. We found that the clinical and biological characteristics showed no significant differences related to the outcome. lmmunochemotherapy treatment may improve response.

[Response to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia]. / Respuesta a inhibidores de tirosina cinasa en pacientes con leucemia mieloide crónica.

BACKGROUND: Chronic myeloid leukemia represents 15 % of all the leukemias in adults. With the introduction of tyrosine kinase inhibitors, overall survival at 10 years is 80-90 %. The objective was to describe the epidemiology, complete cytogenetic response and major molecular response with tyrosine kinase inhibitors in patients with chronic myeloid leukemia. METHODS: It was performed a descriptive cross-sectional study of patients with chronic myeloid leukemia and Philadelphia chromosome-positive in treatment with tyrosine kinase inhibitors. RESULTS: The sample included 54 patients with a mean age of 41 years; 78 % of patients were in chronic phase, and in 8 % of patients were identified complex karyotype at diagnosis. All patients received imatinib as first-line treatment. We identified mutations in 8 %. The patients with primary or secondary resistance (30%) received second-generation tyrosine kinase inhibitors as a second-line therapy. Of 35 patients treated with imatinib, 23 had complete cytogenetic response, 23 had major molecular response, and 16 had loss of response to treatment. Of nine patients treated with nilotinib, two presented complete cytogenetic response, two major molecular response, and five loss of response to treatment. Of seven patients treated with dasatinib, two had complete cytogenetic response, two major molecular response, and four loss of response to treatment. CONCLUSIONS: Of patients studied, 30 % was resistant to imatinib, 52 % achieved a complete cytogenetic response, and 42 % major molecular response. The use of second generation tyrosine kinase inhibitors led to obtain a complete cytogenetic and major molecular response in fewer time.

INTRODUCCIÓN: la leucemia mieloide crónica representa 15 % de las leucemias en los adultos. Con los inhibidores de la tirosina cinasa, la sobrevida a 10 años es de 80 a 90 %. El objetivo de esta investigación fue describir las características epidemiológicas, respuesta citogenética completa y respuesta molecular mayor con inhibidores de tirosina cinasa en pacientes con leucemia mieloide crónica. MÉTODOS: se realizó un estudio transversal descriptivo de los expedientes clínicos de pacientes con leucemia mieloide crónica positivos a cromosoma Filadelfia que fueron sometidos a tratamiento con inhibidores de tirosina cinasa. RESULTADOS: se incluyeron 54 pacientes; la edad media fue de 41 años, 78 % estaba en fase crónica y en 8 % se detectaron cariotipos complejos al diagnóstico. Todos recibieron imatinib como tratamiento de primera línea. Se identificaron mutaciones en 8 % de los pacientes. Los pacientes con resistencia primaria o secundaria (30 %) recibieron inhibidores de tirosina cinasa de segunda generación como tratamiento de segunda línea. De 35 pacientes tratados con imatinib, 23 presentaron respuesta citogenética completa, 23 respuesta molecular mayor y 16, pérdida de respuesta. De nueve pacientes tratados con nilotinib, dos presentaron respuesta citogenética completa, dos respuesta molecular mayor y cinco, pérdida de respuesta. De siete pacientes tratados con dasatinib, dos presentaron respuesta citogenética completa, dos respuesta molecular mayor y cuatro, pérdida de respuesta. CONCLUSIONES: 30 % de los pacientes presentó resistencia, 52 % alcanzó una respuesta citogenética completa con imatinib y 42 % una respuesta molecular mayor. El uso de inhibidores de tirosina cinasa de segunda generación permite alcanzar respuestas citogenética completa y molecular mayor en menor tiempo.

Incidence of extramedullary disease in patients with acute promyelocytic leukemia: a single-institution experience.

Using current treatment regimens, over 90% of patients with acute promyelocytic leukemia will achieve complete remission (CR). However, approximately 30% of these patients will relapse, including a small proportion who will develop extramedullary disease (EMD). In this study, we investigated the incidence of EMD in 263 patients with APL who were treated at our institution from January 1990 to May 2008. With a median follow-up of 31 months (range 2 days-203 months), 8 (3%) patients developed EMD. The most commonly affected site was the central nervous system (n = 7). Before developing EMD, one patient had achieved CR with a chemotherapy-only regimen, six patients had achieved CR with all-trans-retinoic acid (ATRA)-based regimens, and one patient had achieved CR with an ATRA plus arsenic trioxide (ATO)-based regimen. The EMD conferred a poor prognosis; five patients died within 4 months of developing EMD. The molecular status did not predict EMD; four patients had a negative PCR for the PML-RARA transcripts prior to relapse with EMD. In conclusion, the incidence of EMD is low. We were unable to identify any specific factors that could predict the development of EMD.

Phase II study of imatinib mesylate as therapy for patients with systemic mastocytosis.

Gain-of-function D816V point mutation within the kinase domain of the transmembrane receptor KIT is found in the great majority of patients with systemic mastocytosis (SM) and is attractive therapeutic target. Twenty patients with SM were enrolled during 2003-2005 in phase II clinical trial with imatinib mesylate (400mg daily), a KIT inhibitor. Median time on therapy was 9 months (range, 0.5-44+). Only one patient, with D816V KIT mutation-negative FIP1L1-PDGFRalpha-negative SM-HES, achieved complete remission (now lasting for 44 months). Six other patients reported symptomatic improvement, including two with D816V KIT mutation-positive SM (one reported improvement in diarrhea and the other in fatigue). Other patients had no benefit. Imatinib was relatively well tolerated. Our study confirms that imatinib therapy does not result in appreciable clinical activity in patients with D816V mutation-positive SM, but may result in a significant benefit in occasional patient with D816V mutation-negative SM.

Secondary myelodysplastic syndrome in a patient with Philadelphia-positive acute lymphoblastic leukemia after achieving a major molecular response with hyperCVAD plus imatinib mesylate.

The addition of imatinib to high-intensity chemotherapy has improved the outcome of patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, the possible long-term side effects of this combination are not yet known. Development of new clonal abnormalities in complete cytogenetic remission after treatment with imatinib has been reported in patients with chronic myeloid leukemia but not in patients with Ph-positive ALL. Here, we present a patient with Ph-positive ALL who received hyperCVAD plus imatinib and achieved hematologic, cytogenetic, and major molecular responses. The patient then developed myelodysplastic syndrome and solitary central nervous system relapse of ALL.