In patients with acute leukemia (AL), coagulation disorders, which include both thrombotic and hemorrhagic events, are part of the clinical spectrum both at diagnosis and during its evolution. The incidence of these events has been reported by several authors in the range of 1-36 %. This heterogeneity appears to be related to the type of patients included, the study design, and patient-related factors as well as the treatment used. The pathophysiology of thrombosis in AL is complex and multifactorial and includes a myriad of factors that contribute to cancer procoagulant state: synthesis of procoagulant factors by circulating blasts, cellular microparticles, use of endovascular devices (catheters), type of chemotherapy used (L-asparaginase) to name a few. Currently, treatment relies in the use of heparin, followed by vitamin K antagonists for 3 to 6 months. However, randomized controlled studies are required in patients with AL and thrombosis to confirm its safety, duration, and effectiveness.
Introduction: To date, worldwide, the main source of stem cells is peripheral blood (PBSCs). However, its use has been associated with a higher incidence of graft versus host disease (GVHD) when compared with the use of bone marrow. It has been demonstrated that the fast engraftment using G-CSF-primed bone marrow as a source of stem cells, compares to that seen with PBSCs, and it is also associated with a decreased incidence of GVHD. Objective: To describe the results obtained from allogeneic, G-CSF-primed bone marrow transplantations, at INCMNSZ, from November 1998 to March 2013. Material and methods: A retrospective analysis was performed in patients who underwent allogeneic, G-CSF-primed bone marrow transplantation. Clinical characteristics, frequency of GVHD, and survival, were conducted, using the Statistical Software Package SPSS v21.0. Results: Forty-nine patients who underwent allogeneic, G-CSF-primed bone marrow transplantation, from November 1998 to March 2013, were included. Patients (male, 63%) had a median age of 29 years (range 16-59). The patients had a following range of underlying diseases: aplastic anemia (n=15, 30.6%), myelodysplastic syndrome (n=12, 24.5%), chronic myeloid leukemia (CML, n=9, 18.4%), acute lymphoblastic leukemia (LLA, n=7, 14.3%), acute myeloid leukemia (AML, n=3, 6.1%), or others (n=3, 6.1%). Patients achieved a bilineage engraftment with a median time of 20 days (range, 11-40) for absolute neutrophil count and 15 days (range, 5-45) for platelets. Acute GVHD was observed in 4 patients (8.2%), reported as grade I and II; and 14 patients (28.6%) experienced a limited form of chronic GVHD. Nine out of 49 (18.3%) patients relapsed: CML (n=5), AML (n=1), AA (n=1), ALL (n=1), others (n=1). All patients with relapsed CML were treated with donor lymphocyte infusions, but only 2 responded. Treatment related mortality (TRM) was 8.16%, including infectious complications in 2 patients, cGVHD in one patient, and veno-oclussive disease (VOD) in one patient. Overall mortality was 26.5%; the majority of deaths (69.2%) were caused by progressive and relapsing disease. With a follow up of 43 months (0-149), the median overall survival (OS) has not been reached; however, the estimated 10-year OS is 69%. Conclusion: According to our data, it seems that G-CSF-primed bone marrow is a better source of hematopoietic stem cells for allogeneic transplantation in malignant and non-malignant hematological disorders, when compared with PBSCs, due to the similar engraftment time, and a decreased incidence and severity of acute and chronic GVHD. Nevertheless, this strategy does not appear to be valid as an approach for diseases were graft versus tumor effect (GVT) is important to eradicate the malignancy, such as in CML. Disclosures No relevant conflicts of interest to declare.
BACKGROUND: The cytogenetic aspects of acute leukemia have been studied for over 30 years. Genomic sequencing has permitted the identification of recurrent mutations that have been associated with the heterogeneous behavior of acute leukemia. Currently, the genomic profile of patients with acute leukemia is important regarding risk classification and therapeutic approach. At this moment there are scarce studies of the genomic profile in adult patients with acute leukemia in Mexico. OBJECTIVES: To describe genomic alterations found in adult patients with acute leukemia in a cancer reference hospital in Mexico. Evaluate the efficacy of a commercial multiple PCR and nested qualitative PCR kit (HemaVision DNA Technology A/S, HV01-28N), for the detection of 28 translocations on acute leukemia. To assess by a quantitative method with RT-PCR the detection of the most frequently reported mutations in acute myeloid leukemia(38%) [t(15;17) PML-RARa, inv(16) CBF-MYH11, t(8;21) RUNX1-RUNX1T1 and acute lymphoid leukemia (32%) [t(9;22) BCR/ABL, t(4;11) MLL-AFF1, t(1;19) TCF3-PBX1]. Compare the results between the commercial kit, RT-PCR and conventional cytogenetic studies. METHODS: Patients with recent diagnosis of acute leukemia (myeloid and lymphoid) according to World Health Administration (WHO) 2008 criteria were included between the period of 03/25/2013 and 12/15/13. All patients were given informed consent form and approval of the local Ethics Committee We performed bone marrow smear and bone marrow biopsy of all patients. 5 mL of bone marrow were collected on heparin for cytogenetic study including karyotipe and FISH analysis. 5 mL of bone marrow were collected for molecular biology studies including PCR-kit and genome sequencing technique. 5mL of peripheral blood with heparin were obtained for karyotype in case of not finding metaphases for the analysis on bone marrow specimen. RESULTS: 24 patients were enrolled on the study. The mean age was 42 years (17-69). 8/24 were male (33.3%) and 16/24 were female (66.6%). Acute myeloid leukemia 11/24 (45.8%), acute lymphoblastic leukemia 8/24 (33.3%), acute promyeolocytic leukemia 3/24 (12.5%), acute biphenotypic leukemia 1/24 (4.2%) and one case of blastic phase of chronic myeloid leukemia (4.2%). The commercial PCR platform detected only two of the 28 translocations in 4/24 patients (16.6%). 2/24 (8.3%) BCR-ABL and 2/24 (8.3%) PML-RARa. In contrast to RT-PCR that detected 7/24 patients (29%). 4/24 (16%) BCR-ABL, 2/24 (8.3%) PML-RARa and 1/24 (4.1%) CBFB-MYH11. FISH analysis detected the 4/24 (16%) translocations of the commercial kit. Karyotype detected structural chromosomal anomalies in 9/24 patients (37.5%). After the analysis of the 24 samples by quantitative RT-PCR for the six most frequent rearrangements, we also identified 2 additional cases of BCR-ABL. CONCLUSIONS: The commercial qualitative PCR kit was inferior on detecting genomic alterations (16.6%) than quantitative PCR (29%) or conventional cytogenetic study (37.5%). The RT-PCR quantitative method with specific probe for the most frequent genomic alterations in acute leukemia in addition to cytogenetic analysis seems to be a better cost-effective strategy than the commercial multiple PCR platforms. Disclosures No relevant conflicts of interest to declare.
Introduction Hematopoietic stem cell transplantation (HSCT) has become an important strategy for treatment of several diseases. However, in developing countries access is often limited by socioeconomic factors. The information about the costs of the procedure in Mexico is scarce which limits the development of public policies in the area. Objective Describe overall costs of HSCT as well as specific costs of resources used in a tertiary care center in Mexico City. Material and Methods Retrospective, descriptive, observational study. We calculated the median overall cost per transplant in the first 30 days and the median cost per resource category, using SPSS version 17. Results We evaluated a total of 50 TCPH from June 2010 to December 2012. Of all the procedures, 68% were autologous. The median cost for allo-HSCT was $ 24.910 USD, while for auto-HSCT was $14.742 USD. Specific charges were divided into the following areas: for allo-HSCT, conditioning chemotherapy and mobilization: $ 4.087 USD, hospitalization: $ 8.130 USD, laboratory studies: $ 3.922 USD, imaging: $ 1.012 USD, other medications: $ 5.278 USD, blood bank: $ 2.478 USD. For auto-HSCT, conditioning-mobilization: $ 4.997 USD, hospitalization $ 4.086 USD, laboratory $ 1.612 USD, imaging: $ 411 USD, other medications: $ 3.024 USD, blood bank: $ 611 USD. Estimated 5 year-overall survival for these patients was 71.6%. Conclusions These results contribute to the scarce information regarding costs of HSCT in our country. The cost of HSCT in INCMNSZ (government institution) is 10 times lower than in the U.S. with similar results regarding overall survival. These facts highlight the important role of non-profit institutions that contribute to the development of these programs. Disclosures: No relevant conflicts of interest to declare.
4138 Background: Allogeneic stem cell transplantation (ASCT) is the standard treatment for several diseases. However, the morbidity and mortality associated with the procedure limit its widespread use in developing countries. We implemented a novel conditioning method to reduce complications and improve survival. We hypothesized that the dose reduction in this regimen (about 20–25%), would preserve its myeloablative and immunosupressive effect, but with significantly reduced toxicity and mortality. Objectives: Describe clinical characteristics, toxicity, frequency of GVHD and survival of adult mexican patients undergoing ASCT using reduced BUCY2 and G-CSF primed bone marrow as a conditioning method. Material and Methods: Prospective cohort study of patients with matched related donor allotransplant using this new method from November 1999 to December 2011. Stem cell collection was obtained from iliac crests by multiple aspiration. The donor received GCS-F (10μg/kg/day) 3 to 5 days prior to harvest. The conditioning included: Busulfan 12mg/kg PO (3mg/kg/d in -7, -6, -5, -4), Cyclophosphamide 80mg/kg IV (40mg/kg/d in −3, −2), and GVHD prophylaxis with Cyclosporine A (1.5mg/kg bid, beginning at -1: target 200–300 ng/μL) and a short course of Methotrexate. All patients received antimicrobial prophylaxis once the neutrophil count reached < 500/μL. Weekly CMV antigenemia was performed until the 4th month post-transplant. Neutrophil and platelet engraftment were defined as the first of three consecutive days with a neutrophil count □ 0.5 × 109/L and □ 20 × 109/L without transfusion, respectively. Transplant related mortality was defined as any death directly attributed to the conditioning regimen, to aplasia during transplant and/or to infectious or GVHD complications. Engraftment failure was defined as the inability to achieve neutrophil and platelet engraftment during the first 28th days postransplant. Statistical Analysis: Descriptive analysis was used for continuous and categorical variables. Kaplan–Meier curves to asses overall survival, and central tendency measures to analyze: general features, time of engraftment and hospitalization days (SPSS 17.0). Results: 29 patients undergoing ASCT with reduced BUCY2 and GCS-F primed-bone marrow were included. All had a HLA-matched related donor, median age of 29 years. 19 patients (65.5%) were male. The diagnosis was: MDS in 10 patients (34.5%), CML in 9 (31%), ALL in 6 (20.7%), AML in 2 (6.9%) and PNH in 2 (6.9%). The median CD34+ transfused cells: 1.9 × 106/kg. Median time to neutrophil and platelet recovery: 20 days (range 14–29) and 15 days (range 7–36), respectively. All patients engrafted. The most common toxicity was mucositis (79.3%) with grade III-IV in 48.3% of cases. Hepatic (41.4%) and renal (48.3%) toxicities, were mild, transient and easily managed with support measures (table 1). Acute and chronic GVHD developed in 6.9% and 34.5% of patients, respectively. There was no mortality at 30 days, and 100-day mortality was 7% (2 patients), attributed to infectious complications. Transplant related mortality was 10% (3 patients) and 5-year overall survival was 70.3%. Discussion and conclusions: Our results show some advantages compared with standard regimens: noteworthy 5-year OS (70%), similar time to engraftment as for HSC from peripheral source and low GVHD incidence. There was a low TRM (10%), compared to myeloablative regimens, and probably lower than reduced intensity transplants. Main toxicities were grade II-III mucositis and hepatic toxicity, without serious clinical significance. Also, there was a low incidence of acute GVHD (6.9%) probably related to reduced tisular toxicity associated to the conditioning dose reduction, as well as the use of primed bone marrow. In conclusion, this strategy preserves an immunosuppressive and cytotoxic effect allowing eradication of the malignant clone with adequate bone marrow engraftment, acceptable toxicity, low incidence of GVHD and low TRM, representing a new alternative for ASCT. Disclosures: Armengol-Alonso: European Society of Clinical Oncology: Fellowship Other. Neme-Yunes:Agrupación Mexicana para el Estudio de la Hematología: Employment.
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