Background: Persons with multiple sclerosis are increasingly treated with intermediate-or high-dose chemotherapy and a hematopoietic cell autotransplant. This is often done in an inpatient setting using frozen blood cell grafts.Objective: Determine if chemotherapy and a hematopoietic cell autotransplant can be safely done in an outpatient setting using refrigerated, non-frozen grafts. Methods:We developed an autotransplant protocol actionable in an outpatient setting using a refrigerated, non-frozen blood graft collected after giving cyclophosphamide, 50 mg/kg/d × 2 days and filgrastim, 10 μg/kg/d. A second identical course was given 9 days later followed by infusion of blood cells stored at 4°C for 1-4 days. The co-primary outcomes were rates of granulocyte and platelet recovery and therapyrelated mortality. Results:We treated 426 consecutive subjects. Median age was 47 years (range, 21-68 years). A total of 145 (34%) were male. Median graft refrigeration time was 1 day (range, 1-4 days). Median interval to granulocytes >0.5 × 10E + 9/L was 8 days (range, 2-12) and to platelets >20 × 10E + 9/L, 8 days (range, 1-12). Only 15 subjects (4%) were hospitalized, predominately for iatrogenic pneumothorax (N = 5) and neutropenic fever (N = 4). There was only 1 early death from infection. Conclusion:Intermediate-dose chemotherapy and a hematopoietic cell autotransplant can be safely done in an outpatient setting using, refrigerated, non-frozen grafts.

In 1963 Jean Bernard introduced the concept of “geographic hematology” and distinguished 2 branches, i.e., “ethnic hematology,” which deals with differences between populations, and “environmental hematology,” which considers factors such as food habits, infections, and others. Both of these branches have implications in the distribution of hematological diseases worldwide. In comparison with Caucasian populations, in Mexico a significantly higher prevalence of acute lymphoblastic, acute promyelocytic, and acute megakaryoblastic leukemias has been described. The rate of chronic myeloid leukemia seems to be as high as that reported in Caucasian populations, while other myeloproliferative neoplasias are significantly less frequent in Mexico. Significantly lower prevalences of hairy cell leukemia, chronic lymphocytic leukemia, multiple myeloma, and Waldenström’s macroglobulinemia have been reported from Mexico. Regrettably, the influence of drug companies interested in selling their new and expensive drugs has resulted in both overdiagnosis of some diseases and overidentification of the refractory forms of some of these conditions to justify the use of unnecessary drugs.

In order to reset the immune system to baseline function, autologous hematopoietic stem cell transplantation (HSCT) has been performed in patients with multiple sclerosis (MS). After June 2015, 617 new consecutive patients with MS were autografted in our center with non-frozen peripheral blood stem cells. The autografts were performed on an outpatient basis, after conditioning with cyclophosphamide and rituximab. The aim of the study was the assessment of both safety and efficacy of the method. The study's primary co-end-points were recovery of granulocyte and platelet counts and transplant-related mortality. Secondary endpoints were overall survival and clinical response (improvement or stabilization of the self-reported expanded disability status scale score). The protocol was registered in ClinicalTrials.gov identifier NCT02674217.0. We included 401 females and 216 males, with a median age of 46 years. A total of 259 patients had relapsing-remitting MS (RRMS), 228 had secondary progressive (SPMS) and 130 had primary progressive (PPMS) multiple sclerosis. All procedures were initially performed on an out-patient basis and only 32 individuals (5%) required hospitalization. One to three aphereses (median 1) were required to harvest at least 1 × 10 6 /kg viable CD34 + cells. The total number of viable CD34 + infused cells ranged between 1 and 37·83 × 10 6 /kg (median 5·68). Patients recovered more than 0·5 × 10 9 /l absolute granulocytes by day 8 (median, range = 2-14), and platelet values were above 20 × 10 9 /l by day 4 (median, range = 0-11). Eleven individuals required red blood cells and six needed platelet transfusions. To date, there have been no deaths attributable to the transplant, yielding a 30-month overall survival of 100%. Patients have been followed for 3-42 months (median = 12). The overall response rate (decrease or stabilization of the self-reported EDSS score) at 12 months was 78% for all patients (83% in RRMS, 78% in PPMS and 73% in SPMS), while the disability progression-free survival was 82% for all patients (86% in RRMS, 78·5% in SPMS and 78% in SPMS). Changes in the self-reported EDSS score in parallel with neurological improvement were observed in people with all types of MS after HSCT, employing the 'Mexican method' .

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The sticky platelet syndrome (SPS) is a common cause of both arterial and venous thrombosis, being a dominant autosomal disease with qualitative platelet alterations and familial occurrence. It is characterized by platelet hyperreactivity with increased platelet aggregability in response to low concentrations of platelet agonists: epinephrine, adenosine diphosphate, or both. The clinical manifestations involve venous or arterial thrombosis, recurrent pregnancy loss, and fetal growth retardation. To analyze the localization of the thrombotic episodes in a cohort of Mexican mestizo patients with SPS. Between 1992 and 2016, 86 Mexican mestizo patients with SPS as the single thrombophilic condition were prospectively identified; all of them had a history of thrombosis. There were 15 males and 71 females. The thrombotic episodes were arterial in 26 cases and venous in 60 (70%). Arterial thrombosis was mainly pulmonary thromboembolism, whereas venous thromboses were identified most frequently in the lower limbs. Mexican mestizo population with SPS is mainly female; the type I of the condition is the most frequent; both arterial and venous thrombosis can occur, and they are mainly pulmonary embolism and lower limbs venous thrombosis, respectively.

Introduction:The spectrum of multiple sclerosis (MS) among all its clinical types includes a vast number of alterations. Of these, respiratory impairment carries big implications since this is an important cause of mortality and morbidity. Methods: Here, we present an observational study of respiratory assessment through spirometry in individuals with MS. Subjects who underwent autologous hematopoietic stem cell transplant from an interventional study were considered to participate. Results: An abnormal pattern of respiratory impairment was found in 147 participants; of this, 89.6% and 10.4% manifested a restrictive and obstructive pattern, respectively. The restrictive pattern was observed in 58 patients with secondary-progressive MS (SPMS) followed by 36 in patients with relapsing-remitting MS (RRMS) and, finally, 37 in patients with primary-progressive MS (PPMS). The full population had a mean forced expiratory volume of the 1 st s (FEV1) of 92%, while the RRMS, PPMS, and SPMS groups had 93%, 89%, 91%, respectively. The median FEV1/forced vital capacity (FVC) ratio was 82.8% in the full cohort, 83.3% in the RRMS group, 83% in the PPMS group, and 82% in the SPMS group. Negative correlations were found between predicted FVC and FEV1 with expanded disability status scale and FEV1/FVC. Conclusion: This study showed a considerable number of restrictive patterns among all the participants, being the SPMS the type of MS with higher respiratory involvement and with functional disability.

Background. High-dose cyclophosphamide and a haematopoietic cell autotransplant is an effective therapy of multiple sclerosis (MS). This is often done in an inpatient setting using frozen blood cells either blood or bone marrow cells. Objective. Determine if this procedure can be safely and effectively simplified. Methods. We developed an autotransplant protocol actionable in an outpatient setting using refrigerated blood cells collected after giving cyclophosphamide, 50 mg/kg/d x 2 d and filgrastim, 10 μg/kg/d. A 2nd identical dose of cyclophosphamide was given 9 d later followed by infusion of blood cells stored at 4º C for 1-4 d. Subjects received rituximab after bone marrow recovery, 100 mg, every 2 mo for 1 y or rituximab, 1 g in 1 dose based on the subject's residence country (Figure 1). The co-primary outcomes were rate of bone marrow recovery and therapy-related mortality (TRM). Secondary outcomes included MS relapse-free survival (MS-RFS) and survival. Cumulative dose of cyclophosphamide was 200 mg/Kg Results. We treated 426 consecutive subjects. Median age was 47 y (range, 21-68 y). 145 (34%) were male. 84 (20%) had primary progressive MS, 173 (41%), relapsing remitting MS and 169 (39%), secondary progressive MS. Median blood cell storage time was 1 d (range, 1-4 d). Median intervals to granulocytes >0.5 x10E+9/L was 8 d (range, 2-12) and to platelets >20 x10E+/L, 8 days (range, 1-12). 412 subjects (96%) were treated as outpatients. Median follow-up is 6 mo (range, 3-30 mo). There was 1 death from TRM. In 304 subjects (71%) with data from neurologic evaluations ≥3 posttransplant median MS RFS is 27 mo (95% confidence interval [CI], 24, 30 mo). Estimated 1 y MS RFS is 85% (80, 90%) with no significant difference between the 3 MS variants. Median survival will exceed 30 mo. An unusual aspect of our study was giving two 2-d blocks of cyclophosphamide 8 days apart rather than 4 d continuously done for 3 reasons: (1) use of cyclophosphamide to mobilize blood cells for the autograft; (2) facilitate using a refrigerated rather than frozen autograft; and (3) decrease toxicity. Our finding of rapid bone marrow recovery using refrigerated grafts is like our experience in persons with plasma cell myeloma and lymphomas receiving high-dose therapy and an autotransplant. Conclusion. The strategy we developed was actionable in an outpatient setting with rapid recovery of granulocytes and platelets and only 1 early death. Estimated MS-RFS and survival were good. MS variant type did not correlate with MS-RFS or survival. Disclosures Gomez-Almaguer: AbbVie: Consultancy; Novartis: Consultancy.

Background: There are well-established prognostic factors for predicting the overall survival (OS) of patients involved by diffuse large B cell lymphoma (DLBCL). These prognostic factors are age, performance status (PS; ECOG score), high serum lactate dehydrogenase level (LDH), advanced disease (Ann Arbor stage: III, IV) and extranodal sites involved (EN). The patients are distributed in different risk groups according to the score obtained and as established by each research group who developed each international index. However, these prognostic indexes do not explore new markers and just readjust the five known variables since 1993 when The International Non-Hodgkin's Lymphoma Prognostic Factors Project was developed. Serum albumin (SA) has been shown to be a prognostic biomarker in DLBCL prior to R-CHOP treatment (Ngo et al. Leuk Lymph 2008). In another study of patients older than 80 years receiving R-miniCHOP treatment, SA ≤3.5 g/dl was the only factor with a significant effect on OS on (Peyrade et al Lancet Oncol 2011). Studies of non-Hodgkin's lymphoma reported that SA <3.0 g/dl was one of the factors predicting early death from aggressive disease treated with ACVBP (Dumontet et al. Br J Haematol 2002). Another study found that SA <3.7 g/dl is an independent prognostic indicator in DLBCL patients treated with R-CHOP (Dalia et al. Ann Hematol 2014). Aims. The present study evaluates the behavior of IPI, RIPI and NCCN-IPI risk groups obtained from a database of 855 patients involved by DLBCL and explores a cut-off for SA and the addition of it as part of those risk groups. Methods. Seven databases were obtained from different public and private institutions in the country with patients diagnosed with DLBCL. Creating a unique database with 855 patients. Only 811 patients had serum albumin levels in their record (94.8%). Statistical methods: First, we decided to obtain the SA cut-off through the Received Operating Curve because any study has evaluated this (including sensibility, specificity, likelihood ratio positive and negative). Thus, we evaluated the influence of SA in OS. For that, OS was assed using Kaplan-Meier method (KM) and compared between obtained groups using log rank-test. Subsequently, we add SA score to the different risk prognostic index groups and were assed using KM again. Hazard ratio was evaluated using cox-regression model (CRM). Outcomes. From 2008 to 2016 were included from seven different databases in one, 855 patients of different institutions (publics, academics and privates) in different States. Demographic characteristics: Female,51.46%; Median age was 63 y/o (range: 18-96), ≥ 60, 54.8%; PS, ECOG ≥2,31.1%; EN ≥ 1, 32%; LDH > normal, 52.74%. Type of regimen: Rituximab + anthracycline-based regimen= 75%, anthracycline-based regimen=10.5%, rituximab + CVP= 7%, Other treatments=4.5%, No treatment= 3%. All of them were included as intent-to-analyses. The classical variables were evaluated using the CRM, for IPI and RIPI; age and LDH were evaluated according to the proposed cut-off or ratio respectively in the original paper for NCCN-IPI, confirming that all were significant as predictor factors (p <0.0001). The Area under the curve for SA in relation to OS was 0.70 (CI95% = 0.67 to 0.73, p <0.0001) and the cut-off point was <3.2g / dL. However, we observed that SA had two cut-off points with different predictive value that perfectly differentiated two groups. These points were for low group: 3.2 g / dL to 2.5 g / dL (PPV=68%, NPV= 68.1%) and for very low group: ≤2.4 g/dL (PPV=80% , NPV=60.5%). Then, we evaluated its influence in OS, normal SA was 64% ±0.02 vs low group 34%±0.03 (HR=2.6, CI95%=2to3.5) vs. Very low group 16%±0.04 (HR=4.5, CI95%=3to7). For the addition of SA to IPI, RIPI and NCCN-IPI, we gave a 1 point to Low and 2 points to very low; Then, these points were added to the risk scores of the different IPI, which increased the final scores or not. In Table 1, the percentages of OS of each risk group can be compared before and after adding the points according to the SA score. Where adding SA significantly improves the distribution of risk groups. See table 1. Conclusion: SA is an important predictive factor of OS in patients involved by DLBCL. Two risk groups can be observed according to the SA level. The addition of SA to the prognostic indexes improves the distribution of patients and the OS percentage at 5 years of follow-up. Figure. Figure. Disclosures Gomez-Almaguer: AbbVie: Consultancy; Novartis: Consultancy.