Prevalence and Clinical Significance of FLT3 Mutation Status in Acute Myeloid Leukemia Patients: A Multicenter Study.

BACKGROUND AND AIMS: FLT3-ITD mutations in acute myeloid leukemia (AML) are associated with a poor prognosis. In Latin America, little epidemiological data exist about these mutations and their influence on clinical evolution and prognosis. Standardization and well-established clinical correlation make FLT3 mutational analysis by molecular methods an invaluable tool to decide among treatment options and to determine AML prognosis. METHODS: We assessed the prevalence of FLT3-ITD mutations in 138 patients with AML at four hematology referral centers from Mexico and Colombia. Molecular methods based on polymerase chain reaction (PCR) were employed for determining FLT3-ITD status. RESULTS: Mutations were present in 28 patients indicating a prevalence of 20.28%. Median age was 47 years (5-96). The FLT3 mutation positive group was older, had higher WBC and hemoglobin values and lower platelet counts but without statistical significance. A not previously described mutation in the FLT3 gene was found in one patient involving a nucleotide exchange of timine for cytosine at the 66608 position. A high mortality was found in the FLT3-mutated group, 67.8 vs. 42.72% in the non-mutated group and median survival was 4.9 months vs. 20.4 months, p = 0.009. A mutated FLT3 did not confer poor prognosis to those with M3 AML. The mutated FLT3 population had poor overall survival (OS) despite hematoprogenitor stem cell transplantation (HSCT). CONCLUSION: Prevalence of FLT3-ITD mutation in AML was present in a proportion comparable to other populations and, when present, was associated with a very poor prognosis.

CD20 expression in B-cell precursor acute lymphoblastic leukemia is common in Mexican patients and lacks a prognostic value.

Classification of acute lymphoblastic leukemia (ALL) by flow cytometric immunophenotyping characterizes the disease and delineates potential therapeutic intervention. We retrospectively analyzed CD20 expression in 143 patients with newly diagnosed precursor B-cell ALL. CD20 was observed in 61% of patients at diagnosis. There was no correlation between CD20 expression and age, white blood cell count, or cytogenetic abnormalities. Despite the fact that CD20-positive ALL patients had a tendency toward a worse outcome, there was no significant difference between patients with and without CD20 expression in 3-year overall survival 65 vs. 82% (P = 0.14), and cumulative incidence of relapse 36 vs. 18% (P = 0.3) in pediatric patients and 51 vs. 53% (P = 0.31) and 35 vs. 38% (P = 0.6) in adults, respectively. In conclusion, CD20 expression appears to be more common in Mexican patients with newly diagnosed precursor B-cell ALL higher than in Caucasian populations and lacks prognostic value.

Moderate hyperprolactinemia is associated with survival in patients with acute graft-versus-host disease after allogeneic stem cell transplantation.

Fasting serum prolactin (PRL) levels in response to metoclopramide (MCP) and lymphocyte cytokine profiles was studied in patients given allografts and their donors. Thirty normoprolactinemic volunteers (12-59 years) were studied: group 1, 10 healthy men; group 2, 8 males and 2 females with various hematologic diseases; and group 3, 3 males and 7 females HLA-identical sibling donors: PRL and cytokines were measured. Four surviving recipients developed acute graft-versus-host disease (GVHD) (+), and six did not. Before transplant Fasting PRL concentrations were higher in 'future' GVHD(+) recipients than in their donors (P < 0.001). The opposite was seen in response to MCP (P = 0.01). Donors had a predominant T-helper type 1 (Th1) cytokine profile compared with recipients (P ≤ 0.02), and GVHD(+) recipients had a greater tumor necrosis factor (TNF) value than GVHD(-) (P = 0.05). After transplant On days +30 and +100, a mild sustained rise in fasting PRL levels occurred only in GVHD(+) recipients (P ≤ 0.05) simultaneously with a transient rise in Th1 cytokines. GVHD(-) recipients had no changes. Donors with a Th1 cytokine profile might be more prone to induce GVHD in their recipients, and a mild sustained rise in PRL concentrations after transplantation in recipients GVHD(+) might participate in the amelioration of the severity of GVHD.

Core binding factor acute myeloid leukemia (CBF-AML) in México: a single institution experience.

Twenty one patients with CBF-AML presented prospectively in the Centro de Hematología y Medicina Interna de Puebla (Puebla, México) between February 1995 and March 2010, 14 with the t(8;21)(q22;q22) and 7 with the inv(16)(p13;q22)/t(16;16)(p13;q22); they represent 13% of all cases of AML. The median age of the patients was 24 years (range 1 to 61). Seven of 14 patients with t(8;21)(q22;q22) had an M2 morphology whereas 3/7 with the inv(16) had an M4 morphology; in addition to the myeloid markers identified by flow-cytometry (surface CD13, surface CD33, and cytoplasmic myeloperoxidase) lymphoid markers were identified in the blast cells of 8/14 cases of the t(8;21) patients, but in no patient with the inv(16). Nineteen patients were treated with combined chemotherapy and 16 (84%) achieved a complete molecular remission. Seven patients were auto or allografted. Relapses presented in 10/16 patients. The median probability of overall survival (OS) has not been reached being above 165 months, whereas the 165-month probability of OS and leukemia-free survival was 52%; despite a tendency for a better outcome of patients with the t(8;21), there were no significant differences in survival of patients with either the t(8;21) or the inv(16). In this single institution experience in México, we found that the CBF variants of AML have a similar prevalence as compared with Caucasian populations, that the co-expression of lymphoid markers in the blast cells was frequent in the t(8;21) and that these two AML subtypes were associated with a relatively good long-term prognosis. Further studies are needed to describe with more detail the precise biological features of these molecular subtypes of acute leukemia.

Romiplostin may revert the thrombocytopenia in graft-versus-host disease.

The thrombocytopenia ensuing during acute graft-versus-host disease (GVHD) is multifactorial and may significantly compromise the prognosis of the patient; non-immune persistent thrombocytopenia has been considered as an adverse prognostic factor in GVHD. We describe here the case of a 10-year-old girl who developed steroid-refractory thrombocytopenia and who responded promptly to the subcutaneous delivery of romiplostin. To the best of our knowledge, this is the first description of the usefulness of the peptibody in the setting of GVHD.