Diagnosing and treating mixed phenotype acute leukemia: a multicenter 10-year experience in México.

Mixed phenotype acute leukemia (MPAL) in adults represents nearly 2 to 5 % of all acute leukemia cases. There are two large studies throughout the world and only case reports and small series have been reported in Latin America. This study retrospectively analyses the clinical characteristics and survival of 27 patients with MPAL evaluated in three medical institutions of Mexico. All cases meet World Health Organization 2008 criteria; 70.3 % of patients had B lymphoid/myeloid lineage MPAL. Induction chemotherapy protocols included 7 + 3 hyper-CVAD, high-density schedules, and pediatric-like regimens such as New York II and total XI. Complete remission was achieved in 23/27 patients (85.2 %). Only one patient died due to chemotherapy-induced aplasia during remission induction (5.2 %). In 68 % of cases, we were able to administer maintenance therapy as a regimen in lymphoblastic leukemia. At the time of analysis, 70.4 % of the patients in the entire cohort had died mainly as result of disease progression (73.6 %). Disease-free survival was 13 months (95 % CI, 9.6-16.3 months) and overall survival was 14.8 months (95 % CI 13.4-16.27). Survival rates are low and standardized therapy for the management of this type of leukemia is still lacking. This is the largest series reported in Mexico and to the best of our knowledge in Latin America.

Oral versus intravenous fludarabine as part of a reduced-intensity conditioning for allogeneic stem cell transplantation.

BACKGROUND: In 2003, oral fludarabine was introduced in the USA for the treatment of patients with hematologic malignancies as an alternative to its intravenous (i.v.) formulation; in 2008, it was introduced in México while the i.v. formulation was withdrawn. Accordingly, i.v. fludarabine had to be replaced by oral fludarabine as part of the conditioning regimen employed to conduct allogeneic stem cell transplantation in México. METHODS: Nonrandomized retrospective analysis of 55 patients conditioned with oral fludarabine compared with 113 patients conditioned with the i.v. formulation. In addition to fludarabine, the conditioning regimen included oral busulfan and i.v. cyclophosphamide. Donors were HLA-matched siblings. RESULTS: The clinical features of the two groups were comparable. There were no statistical differences in time to neutrophil engraftment, time to platelet engraftment, acute graft versus host disease rate and nonrelapse mortality at day 100. The overall survival of patients allografted with oral fludarabine was better than those allografted with i.v. fludarabine: 62 and 33% at 67 months, respectively (p = 0.0006). DISCUSSION: Oral fludarabine can replace its i.v. formulation as part of reduced-intensity conditioning regimens with no deleterious effect on any of the early transplantation outcomes.

Poor performance of the total kappa/lambda light chain quantification in the diagnosis and follow-up of patients with multiple myeloma.

BACKGROUND: The gold standard for paraproteinemia screening in plasma cell disorders has been serum protein electro- phoresis (SPE) with immunofixation electrophoresis (IFx); serum total and free light chain quantifications have also been used. OBJECTIVE: To define the role of SPE, IFx and serum total light chain (sLC) determinations in patients with multiple myeloma (MM), both at diagnosis and at maximum response during treatment follow-up. MATERIAL AND METHODS: These serological studies were performed in a group of 62 patients with MM at diagnosis, and in a subset of 29 patients at the point of maximum response to treatment. RESULTS: At diagnosis, we found an abnormal SPE in 58%, an abnormal IFx in 92% and an abnormal sLC in 45% of the 62 patients; 64% had simultaneously abnormal results in all three serological studies. IFx alone proved to be the most sensitive of all three assays, followed by SPE, which was redundant in most instances with sLC and IFx. At maximum response, the abnormal SPE normalized in 7 cases, the abnormal IFx in 7 cases and the abnormal sLC in 7 cases. There were 12 instances in which an abnormal IFx was found despite normal sLC, and one case in which a normal IFx was found in the presence of abnormal sLC. The association between IFx and sLC was highly significant (r = 0.9274611, p < 0.000001), despite instances where a positive result for IFx was associated to a normal sLC. CONCLUSION: All three serological methods should ideally be simultaneously performed in patients with MM both at diagnosis and throughout therapy. In this series, the total sLC assay was not more sensitive than IFx neither at diagnosis nor during follow-up.

Primary thrombophilia in México X: a prospective study of the treatment of the sticky platelet syndrome.

INTRODUCTION: The sticky platelet syndrome (SPS) is a common cause of thrombosis. There are no prospective studies concerning treatment. OBJECTIVE: To analyze changes in platelet hyperaggregability of patients with SPS who were given antiplatelet drugs and to assess its association with rethrombosis. METHODS: A total of 55 patients with a history of thrombosis and SPS phenotype were prospectively studied before and after treatment with aspirin and/or clopidogrel. RESULTS: Patients were followed for 1 to 129 months, median 13. Of 55 patients, 40 received aspirin, 13 received aspirin + clopidogrel, and 2 received only clopidogrel. The platelet aggregation response to adenosine diphosphate and epinephrine significantly diminished after treatment, and only 2 patients developed rethrombosis 52 and 129 months after starting therapy, with the freedom from rethrombosis rate of the patients being 96.4% at 129 months. CONCLUSION: Using antiplatelet drugs, the platelet hyperreactivity of patients with the SPS phenotype was reverted; and this translated into a substantial decrease in the rethrombosis rate.

Secondary malignancies after allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning and outpatient conduction.

BACKGROUND: Patients given allogeneic hematopoietic stem cell transplants (HSCT) may develop secondary malignant neoplasms (SMN). Several variables have been identified but there are no data about the incidence of this complication in individuals given HSCT using reduced-intensity conditioning (RIC) methods. OBJECTIVE: Define the incidence of SMN in patients given HSCT using a RIC preparative regimen conducted on an outpatient basis. MATERIALS AND METHODS: Patients given HSCT in two institutions between October 1998 and 2012 were analyzed. To appraise the SMN appearance, those patients dead were also regarded as censored at that moment, as well as those lost to follow up and those alive at the closing of the study. 95% Confidence intervals (CI) for the survival or failure estimate were calculated with the Greenwood's method. RESULTS: A total of 416 allografted patients with a Karnofsky performance index of 100% were included in the study. All patients received peripheral blood stem cells allografts. The conditioning regimen was delivered as an outpatient procedure in all individuals. No patient was given radiotherapy nor antithymocyte globulin during the conditioning. Three hundred and sixty five patients (88%) were never admitted to the hospital, whereas 12% were admitted because of grade III-IV acute graft versus host disease (aGVHD), fever, or mucositis. Median survival time was 15.7 months. Survival at 6 months (95% CI): 66.4% (61.5-70.8%), at 12 months: 53.3% (48.1-58.1%), at 60 months: 30.6% (30.5-41.5%). Eight patients with a SMN were identified in the group of 416 allografted patients, SMN rates (95% CI) were: one year post graft: 1.9% (0.7-4.9%), 5 years: 3.8% (1.6-9.2%), 10 years: 6.8% (2.6-17.7%) and 13 years post-graft: 20.2% (5.5-59.2%), the cumulative probability of SMN being 6.8 at 10 years. Since the number of expected cases in the general population is 0.62, the ratio of observed to expected cases is 12.9 (P < 0.001). This figure means that the risk of developing a malignant neoplasm in allografted individuals using our method is 12.9 times higher than that in the general population. There were three non-Hodgkin's lymphomas, two M2 acute myelogenous leukemias, one hairy cell leukemia, one tongue epidermoid carcinoma, and one breast carcinoma. CONCLUSIONS: We have found a low incidence of SMN in this group of Mexican patients allografted with the Mexican RIC method. Possible explanations for this difference are discussed, focusing on the RIC preparative regimen.

In pursuit of the graft-versus-myeloma effect: a single institution experience.

Partly because of a potential graft-versus-myeloma effect, allogeneic stem cell transplantation is a potentially curative treatment modality in patients with multiple myeloma (MM). Initial attempts have been hampered by the high transplant-related mortality in this setting. With a reduction of toxicity, allogeneic transplant approaches with reduced-intensity conditioning (RIC) have been utilized, although they are subjected to continued disease progression and relapse following transplantation. We analyze here the experience of allografting four patients with MM in a single institution, along a 16-year period in which a total of 152 individuals were allografted, using an RIC regimen; three of the patients have had previous autografts. All patients engrafted successfully and a graft-versus-myeloma effect was shown in all of them. One patient relapsed in the face of graft-versus-host disease (GVHD). Three patients have died (two as a result of GVHD) and one is alive with a limited form of chronic GVHD. The graft-versus-myeloma effect can be induced by means of allogeneic transplantation but the morbidity and mortality associated with the procedure leads into a relatively small proportion of MM patients being cured.

Simultaneous romiplostin, eltrombopag, and prednisone were successful in severe thrombocytopenia of Evans syndrome refractory to hydrocortisone, splenectomy, intravenous IgG, and rituximab.

A 58-year-old woman presented with rheumatoid arthritis-associated Evans syndrome (simultaneous autoimmune hemolytic anemia and autoimmune thrombocytopenic purpura); she was treated unsuccessfully with steroids, romiplostin, rituximab, immunoglobulin G, and splenectomy. The platelet count responded to the combined use of prednisone, eltrombopag, and romiplostin. It may be more reasonable to use combined treatments than sequential monotherapies.