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The objective of this study is to explore the possibility of treating APL patients fully as outpatients. A total of 21 consecutive APL patients were identified over 30 years in the Centro de Hematología y Medicina Interna de Puebla, at Clínica Ruiz, but only 17 were studied, treated as outpatients, and followed for at least 1 month; they were observed for median of 95 months, their median age was 27 years and all were treated with ATRA, prednisone, and adriamycin as outpatients. Treatment was completed on an outpatient basis in 15/17 cases. Molecular remission was achieved in 16/17 patients. The median follow-up was 95 months (IQR 19 - 360). The median OS and LFS were not reached, and the 12-month LFS was 94%. We have confirmed that APL can be treated entirely on an outpatient basis: this observation is of utmost relevance in a resource-limited setting, such as those prevailing in low- and middle-income countries.

Haploidentical hematopoietic can be conducted on an outpatient basis but the two main reasons to accept into the hospital a patient in this setting are complications of the hematological toxicity and/or the cytokine-release syndrome. With the aim of reducing the post-transplant cyclophosphamide-dependent toxicity without compromising its effectivity, attempts to reduce the dose of post-transplant cyclophosphamide have been made: Decreases from the conventional total dose of post-transplant cyclophosphamide (100 mg/Kg) have been explored worldwide, showing that decreasing the total dose to even 50 mg/Kg significantly decreases the toxicity of the procedure without compromising its efficacy, safety and results. We present here the salient data of the attempts to diminish the doses of post-transplant cyclophosphamide which have been done and published worldwide, information that suggests that the conventional doses of post-transplant cyclophosphamide can be significantly reduced thus decreasing the toxicity, without compromising the effectiveness of the procedure, mainly the development of graft versus host disease.

Introduction: Biomarkers that help to evaluate the immune system and could be useful in multiple sclerosis (MS) are the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). The objective of this work is to evaluate the significance of the SII index, PLR, and NLR before and after transplantation in individuals with MS who underwent autologous hematopoietic stem cell transplant (aHSCT) at a single institution., Methods: Patients with MS who received an aHSCT between 2017 and 2022 were included in the study. NLR, PLR, and SII index were calculated prior to the transplant and 100 days after, and evaluation of the expanded disability status scale (EDSS) was done before the transplant and 12 months after. The cohort was divided into two groups: aHSCT responders (R) and nonresponders (NR)., Results: Fifty-eight individuals were examined: 37 patients in the responders group R group and 21 in NR group. There was no statistically significant difference in the SII, NLR, and PLR prior to the transplant, however at 100 days post-HSCT, NLR in the R group was 1.8 versus 3.1 in the NR group (p = 0.003), PLR was 194 versus 295, respectively (p = 0.024), meanwhile SII index was 489.5 versus 729.3 (p < 0.001)., Conclusion: High NLR and SII index values after the aHSCT were associated with a worsening in the EDSS score. However, since this is the first ever study that compared NLR and SII index with the aHSCT response in persons with MS, further studies must be performed to corroborate this information., (© 2024 John Wiley & Sons Ltd.)

Background: Multiple myeloma (MM) is a disease with unspecific initial symptoms which may lead into a delay in the diagnosis, seemingly increasing the risk of complications and in turn reducing the overall survival (OS)., Objective: To analyze the consequences of a delayed diagnosis of MM in both the OS and the progression-free survival (PFS) of the patients in a single center in México., Methods: The study included patients with MM who were diagnosed at Clínica Ruiz, Puebla, México, between 1983 and 2022. According to the time elapsed between the onset of symptoms to the establishment of the definite diagnosis of MM, 4 groups were constructed: 1) Less than 3 months, 2) 3-6 months, 3) 6-12 months, and 4) More than 12 months., Results: About 136 patients had a complete clinical record and at least a 3-month follow up period. A delay in the diagnosis of MM (more than 3 months from the onset of symptoms) was recorded in 92/136 persons (68%). The median follow-up for the whole group was 24.7 months, median OS was 131.4 months, whereas median PFS was 85.4 months. There was a significant trend for being in earlier stages of the disease and being diagnosed within 3 months from the onset of symptoms (P = .049). Both OS and PFS were similar in the patients diagnosed before or after 3 months from the symptoms onset (P = .772). The 6-12 months group was the group with the better median both OS (197.4 months) and DFS (197.4) from the diagnosis. The median OS for the other groups were similar among them., Conclusion: A delay in the diagnosis of MM is very frequent in México (68% of cases); despite the fact that there was a significant trend for being in earlier stages of the disease and being diagnosed within 3 months from the onset of symptoms, we did not find a relationship between a delay on the diagnosis of the disease and a higher risk of complications and/or poor prognosis. Possible explanations to these findings are discussed., Competing Interests: Disclosure The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: We have analyzed the association of delayed both diagnosis and treatment of persons with MS with the long-term results of patients given autologous hematopoietic stem cell transplantation (aHSCT)., Methods: Patients with MS referred to the HSCT-Mexico program were included in the study; in 103, detailed pre- and post-transplant evolution could be recorded. Two groups of patients were analyzed according to the time of evolution between the onset of symptoms and the definite diagnosis of MS: more than 8 months (delayed diagnosis, DD), or less than 8 months (non-delayed diagnosis, NDD). The progression of MS was assessed by changes in the expanded disability status scale (EDSS)., Results: The time elapsed between the onset of symptoms and the correct diagnosis was lower for the NDD group (1.55 vs. 35.87 months, p<0.05). Both groups of patients showed a similar EDSS score at diagnosis (1.5 vs. 1.5); however, the EDSS at the time of the transplant was higher in the DD group (4.5 vs. 3.0, p=0.3) and the response of the EDSS score to the transplant was significantly better for the NDD group, the last EDSS scores being 2.5 vs. 4.25 (p=0.03). Both groups of patients responded to aHSCT by diminishing the EDSS, but the response was significantly better in the NDD group., Conclusions: These data indicate that both the pre-transplant progression of the disease and the response to aHSCT were significantly worse in the DD group. An early diagnosis and an early aHSCT intervention are critical for a good prognosis, in terms of lowering and stabilizing the motor disability in MS patients given autografts., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries., Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era., Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed., Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached., Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience., (Copyright: © 2023 Permanyer.)

Immunosuppressive therapy is useful in persons with multiple sclerosis (MS), and autologous hematopoietic stem cell transplantation (aHSCT) is the most effective immunosuppressive treatment in this setting. Information on the usefulness of a second aHSCT in patients with MS is scarce. In a group of 1225 individuals with MS prospectively managed with aHSCT, we analyzed the salient features of 4 patients who received 2 consecutive transplants. After a moderate initial response to the first aHSCT, the patients were transplanted again after deterioration of their neurologic status; the second transplant was well tolerated and, in all instances, was completed on an outpatient basis and with no associated undesired toxicity. The autograft protocol is registered in ClinicalTrials.gov, identifier NCT02674217. After the second graft, the expanded disability status scale score stabilized in 2 patients; in 1, the post-transplant period was too short to assess the response, and in another, the development of associated Parkinson's disease precluded the assessment of the outcome. In conclusion, a second aHSCT in persons with MS is feasible, safe, and may lead to a positive response in some cases., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Abnormal lung function in people with multiple sclerosis (PwMS) could be considered as the result of muscle weakness or MS-specific structural central nervous system (CNS) abnormalities as a precipitant factor for the worsening of motor impairment or cognitive symptoms., Methods: This is a cross-sectional observational study in PwMS. Forced spirometry was conducted, and normative metrics of forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1 ), and the relation FEV1/FVC were calculated. Qualitative and quantitative brain magnetic resonance imaging (MRI) examinations were carried out., Results: A total of 371 PwMS were included in the study. Of those, 196 (53%) had RRMS, 92 (25%) SPMS, and 83 (22%) PPMS. Low FVC and FEV 1 was present in 16 (8%), 16 (19%), and 23 (25%) of the patients in the RRMS, PPMS, and SPMS, respectively. PwMS with T2-FLAIR lesions involving the corpus callosum (CC) had a significantly higher frequency of abnormally low FVC and FEV 1 (OR 3.62; 95% CI 1.33-9.83; p = 0.012) than patients without lesions in that region. This association remained significant in the RRMS group (OR 10.1; 95% CI 1.3-67.8; p 0.031) when the model excluded PPMS and SPMS. According to our study, for every increase of 1 z score of FVC, we observed an increase of 0.25 cm 3 of hippocampal volume (β 0.25; 95% CI 0.03-0.47; p 0.023) and 0.43 cm 3 of left hippocampus volume (β 0.43; 95% CI 0.16-0.71; p 0.002)., Conclusions: We observed an incremental prevalence of abnormally low pulmonary function tests that parallels a sequence from more early relapsing courses to long-standing progressive courses (RRMS to PPMS or SPMS)., (© 2023. Fondazione Società Italiana di Neurologia.)

The severe adult respiratory syndrome virus type 2 (SARS-CoV-2) related acute respiratory distress syndrome (ARDS) has a strong immunological and inflammatory component; accordingly investigators are employing monoclonal antibodies to ameliorate the virus-induced cytokine storm such as antibodies against interleukin 6 (IL-6), tumor necrosis factors alpha (TNF-alpha) and CC chemokine receptor 5 (CCR5) (1). Cyclophosphamide (Cy) has proven its role in various settings including autoimmune diseases, and in the post-haploidentical stem cell transplant setting; Cy depletes cytotoxic and effector T cell populations while relatively sparing the regulatory T cells (Tregs) and could tip the balance away from the overtly pro-inflammatory setting (1). We present here the cases of three persons who were infected by the SARS-CoV-2 virus during the Cy-induced pancytopenia of an autologous hematopoietic stem cell transplantation (HSCT), aimed to down-regulate the immune response in multiple sclerosis (MS) (2). The surprisingly benign course of the COVID-19 in the three cases suggest that the Cy could have had a role in abrogating the inflammatory response in these persons.

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the world's most common treatable neuropathy which usually responds to immunosuppressive treatment. Autologous hematopoietic stem cell transplantation (aHSCT) is an intense way of inducing immunosuppression., Objective: We analyze the evolution of CIDP patients treated with aHSCT in our center., Methods: Between 2018 and 2023, persons with CIDP were prospectively autografted employing the "Mexican method" to conduct grafts on an outpatient basis, employing cyclophosphamide 200 mg/Kg and rituximab 1000 mg. The protocol is registered in ClinicalTrials.gov identifier NCT02674217., Results: In our center 21 autologous transplant cases were completed in 2018-2023. Seven patients provided data to assess the efficacy of the procedure. Positive responses (stabilization and/or improvement) were observed in all seven patients: Five reported improvements in the Inflammatory Neuropathy Cause and Treatment (INCAT) score and one reported stabilization. In the Inflammatory Rasch-Built Overall Disability Scale (I-RODS) score. Median INCAT score was 5 (range 1-9), whereas median I-RODS score was 24 (range 11-29). Five patients (71%) reported improvement in the INCAT score, one reported stabilization and one informed worsening; concerning the I-RODS score 5 (71%) informed improvement, whereas two reported stabilization., Conclusion: aHSCT conducted fully in an outpatient basis, employing the conditioning regimen of the "Mexican method" appears to be a feasible therapeutic option for persons with CIDP. Additional studies are needed to confirm these observations., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest. The authors declare that no patient data appear in this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the most important curative modality for several hematologic malignancies, but an HLA-matched sibling or unrelated donor is not always available, particularly for ethnic minorities and multiethnic families. We have shown that Haplo-HSCT can be conducted safely on an outpatient basis, using peripheral blood stem cells; this leading into substantial decreases in the costs. Methods: In this study twenty-one patients prospectively received the conventional dose of post-transplantation cyclophosphamide (PTCy): (50 mg/Kg on days 3 and 4), whereas 10 were given reduced doses of the drug (25 mg/Kg on days 3 and 4). Results: According to the statistical analysis, the two comparative groups (PTCy 50 mg/kg vs PTCy 25 mg/kg) had no significant difference in terms of age, sex, hematological recovery, and type of conditioning regimen. The median OS for the group PTCy 50 mg/kg is 5.7 months meanwhile for the group PTCy 25 mg/kg the median is 6.4 months. The median follow up for entire group is 4.5 months (IQR: 1.1-18.9 mo). Conclusion: These results could indicate that the Cy-dependent hematological toxicity can be reduced without compromising its effectivity. This preliminary observation may be considered as an idea to conduct prospective randomized studies to explore the possibility of significantly reducing the doses of PT-Cy in the setting of Haplo-HSCT. Trial registration: ClinicalTrials.gov identifier: NCT05780554.

Introduction: Multiple sclerosis (MS) is a disabling disease that affects young adults. Treatments for MS have increased exponentially in number, efficacy and risk. Autologous hematopoietic stem cell transplantation (aHSCT) can change the natural history of the disease. To analyze if aHSCT should be done early in the course of the disease or after failing of other therapies, we have studied the long-term results of aHSCT in a cohort of persons with MS who were given, or not, immunosuppressive drugs before the transplant., Materials and Methods: Patients with MS referred to our center for aHSCT between June 2015 and January 2023 were prospectively entered in the study. All phenotypes of MS were included (relapsing remitting, primary progressive and secondary progressive). The follow up was assessed with the patient reported EDSS score in an online form; only patients followed by three or more years were included in the analysis. Patients were divided into two groups: Given or not disease modifying treatments (DMT) before the aHSCT., Results: 1132 subjects were prospectively enrolled. 74 patients were followed for more than 36 months, and the subsequent analysis was done in this cohort. The response rate (RR = improvement + stabilization) at 12, 24 and 36 mo was 84%, 84% and 58% respectively for patients not receiving prior DMT and 72%, 90% and 67% for patients receiving DMT. In the whole group, the EDSS score dropped from a mean of 5.5 to 4.5 at 12 mo, to 5.0 at 24 mo and to 5.5 at 36 mo, after the aHSCT. The EDSS score was on average worsening in patients before the aHSCT, but the transplant stabilized the EDSS score at 3 years in patients with prior exposure to DMT, whereas in persons not given DMT, the transplant resulted in a significant decrease (p = .01) of the EDSS score. This indicates a positive response in all patients given aHSCT, but significantly better in those not exposed to DMT before the graft., Conclusion: The response to aHSCT was better for persons not exposed to immunosuppressive DMT before the transplant, thus suggesting that aHSCT should be done early in the course of the disease and probably before the treatment with DMT. Additional studies are needed to further analyze the impact of the use of DMT therapies before the aHSCT in MS, as well as the timing of the procedure., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The therapy of children with acute lymphoblastic leukemia (ALL) in limited resource geospaces is challenging and must balance safety, efficacy, availability, and affordability. We modified the control arm of the St. Jude Total XI protocol for outpatient delivery including once-weekly daunorubicin and vincristine in initial therapy, postponing intrathecal chemotherapy until day 22, prophylactic oral antibiotics/antimycotics, use of generic drugs, and no central nervous system (CNS) radiation. Data were interrogated from 104 consecutive children ≤12 years (median, 6 years [interquartile range (IQR), 3, 9 years]. All therapies were given in an outpatient setting in 72 children. Median follow-up is 56 months (IQR 20, 126 months). A total of 88 children achieved a hematological complete remission. Median event-free survival (EFS) is 87 months [95% confidence interval (CI), 39, 60], 7.6 years in low-risk children (3.4, 8 years) whereas 2.5 years (1, 10 years) in high-risk children. The 5-year cumulative incidence of relapse (CIR) is 28% (18, 35%), 26% (14, 37%) in low-risk children and 35% (14, 52%) in high-risk children. Median survival for all subjects is not reached but must exceed 5 years. A total of 36 children relapsed at a median of 12 months (5, 23 months). Outcomes were comparable to those reported in the control arm of the Total Therapy XI study, but inferior to current treatment protocols in high-income countries. The average cost of the first 2 years of therapy was $28,500 USD compared with an average cost of approximately $150,000 USD in the US, an 80% saving. In conclusion, using an outpatient-based modification of the St. Jude Total XI protocol, we obtained good results with relatively few hospitalizations or adverse events and at a substantial saving. This model can be applied in other resource-poor geospaces., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gallardo-Pérez, Gale, Reyes-Cisneros, Sánchez-Bonilla, Fernández-Gutiérrez, Stock, Murrieta-Álvarez, Olivares-Gazca, Ruiz-Delgado, Fonseca and Ruiz-Argüelles.)

Introduction: We have previously shown that some patients present thrombocytopenia (less than 100 × 10 9 /L platelets) in non-alcoholic fatty liver disease (NAFLD). To further explore the nature of this association, we have now analyzed the association of thrombocytopenia with neutropenia (less than 0.5 × 10 9 /L granulocytes) in NAFLD., Material and Methods: Persons with NAFLD were prospectively accrued in the study after February 2018. The presence of NAFLD was defined by both serologic determinations (Fibromax ®) and liver transient elastography (TE/Fibroscan ®)., Results: In 123 consecutive patients with NAFLD without cirrhosis, thrombocytopenia was identified in 20 (16%), whereas neutropenia was identified in 9 (7%). In the subset of 20 patients with NAFLD and thrombocytopenia, granulocytopenia was identified in 5 (25%), whereas in the subset of 9 patients with granulocytopenia, thrombocytopenia was identified in 5 (55%). We found a significant association between thrombocytopenia and both leukopenia and granulocytopenia (OR 8.25, 95% CI 1.9-34.2, p = 0.004)., Conclusions: Both thrombocytopenia and neutropenia were identified in persons with NAFLD and, as there is a significant relationship between these two variables, we speculate that this finding may support the possibility of hypersplenism being involved in the cytopenias found in NAFLD without cirrhosis., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest., (Copyright © 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The outcomes of Hodgkin´s lymphoma (HL) in México have not been widely reported. Simplified and affordable treatments have been adopted in middle-income countries., Aim: The aim was to evaluate long-used therapies for HL in México in a long-term basis., Methods: In a 34-year time period, 88 patients with HL were treated at a single institution in México. Patients were treated with adriamycin bleomycin vinblastine and dacarbazine (ABVD) or mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Relapsed or refractory patients were given ifosfamide, carboplatin, and etoposide (ICE) followed by autologous or allogeneic stem cell transplants., Results: Thirty-seven women and 51 men were included; the median age was 29 years. Patients were followed for a mean of 128 mo. The 310-mo overall survival (OS) was 83% for patients treated with MOPP and 88% for those treated with ABVD. The OS of patients who received autologous stem cell transplantation was 76% (330 mo) vs 93% (402 mo) in those who did not., Conclusion: HL may be less aggressive in Mexican population than in Caucasians. Combined chemotherapy renders acceptable results, regardless of clinical stage., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicting interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

After gaining experience conducting both auto and allografts in persons with hematological diseases in the HSCT programs in Puebla and Monterrey, México, this study outlines subsequent program autografting patients with autoimmune conditions. The first transplant in multiple sclerosis was conducted in Puebla on July 5, 2006. From 2015 we increased activity autografting persons with autoimmune conditions in the two campuses of the HSCT-México program: Puebla and Monterrey. By December 6, 2020, patient number 1,000 in the program was autografted. In our experience, a significant reduction in the expanded disability status scale score was achieved in all of the three phenotypes of the disease (from a median of 5.1 to 4.5 points), whereas the response rate (defined as a decrease of at least 0.5 of EDSS score regardless of baseline EDSS, or unchanged EDSS) was 83, 78, and 73% after 12 months in the relapsing-remitting, primary-progressive and secondary-progressive forms of multiple sclerosis, respectively. In addition to analyzing the viability, safety, and efficacy of our method, this study contributes new knowledge to the field of both stem cell transplantation and multiple sclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Murrieta-Álvarez, Cantero-Fortiz, León-Peña, Olivares-Gazca, Priesca-Marín, Ruiz-Delgado, Gómez-De-León, Gonzalez-Lopez, Jaime-Pérez, Gómez-Almaguer and Ruiz-Argüelles.)

Introduction: Although therapeutic choices for patients with chronic lymphocytic leukemia (CLL) were once limited, treatment of this disease has vastly improved in the last decades. Patients and methods: Consecutive CLL patients diagnosed in a single institution were analyzed. Treatment was withheld in persons with CLL Rai stage 0 or 1, until progression and in persons with stages 2-4, with a negative expression of ZAP-70 until progression. Between 1983 and 1991, patients were give chlorambucil and prednisone (CP); after 1991 fludarabine and cyclophosphamide (FC) and after 1998, rituximab and FC (FCR). Results: 98 patients with CLL were identified; 49 were followed for >3 months. 21 persons (43%) did not require treatment nor progressed; 14 received CP, 6 FC, 7 FCR and one rituximab. Median overall survival (OS) has not been reached, being above 247 months; median OS for patients given CP was 115 months, for FC above 132 months and for FCR above 136 months ( p  > 0.5). Conclusion: CLL seems to be less aggressive in Mexican mestizos than in Caucasians; 43% of patients do not need treatment at all.

Background: The biology of some hematological diseases varies among different populations. No previous studies have evaluated the clinical behavior of mantle cell lymphoma (MCL) in México., Objective and Methods: This is a retrospective review of MCL cases seen in Mexico from January 2003 to June 2020. A total of 12 cases were identified., Results: There were nine males and three females; median age was 56 years. Eight patients had a high MCL international prognostic index score, one was intermediate, and three were low. Five patients had circulating malignant monoclonal cells. Initial treatment included rituximab, cyclophosphamide, daunorubicin, vincristine, and prednisone (R-CHOP) and CHOP. Subsequent treatment included hematopoietic stem cell transplantation in five patients; two were given maintenance therapy. Splenectomy was done in four patients. Median overall survival (OS) for all the patients has not been reached and exceeds 162 mos: OS at 162 mos was 56%. Achieving a complete remission (CR) after the first treatment was a significant prognostic factor, with a median OS exceeding 141 mos in patients achieving CR, and 16 mos among those not achieving CR (p = 0.0006)., Conclusion: Some of MCL patients in Mexico have an indolent clinical course, particularly patients who achieve a CR to initial treatment and who undergo splenectomy.

Background: The ideal treatment of coronavirus disease (COVID)-19 has yet to be defined, but convalescent plasma (CoPla) has been successfully employed., Objective: The objective of the study was to study the safety and outcomes of the administration of CoPla to individuals with severe COVID-19 in an academic medical center., Methods: Ten patients were prospectively treated with plasma from COVID-19 convalescent donors., Results: Over 8 days, the sequential organ failure assessment score dropped significantly in all patients, from 3 to 1.5 (p = 0.014); the Kirby index (PaO 2 /FiO 2 ) score increased from 124 to 255, (p < 0.0001), body temperature decreased significantly from 38.1 to 36.9°C (p = 0.0058), and ferritin levels also dropped significantly from 1736.6 to 1061.8 ng/ml (p = 0.0001). Chest X-rays improved in 7/10 cases and in 6/10, computerized tomography scans also revealed improvement of the lung injury. Decreases in C-reactive protein and D-dimer levels were also observed. Three of five patients on mechanical ventilation support could be extubated, nine were transferred to conventional hospital floors, and six were sent home; two patients died. The administration of CoPla had no side effects and the 24-day overall survival was 77%., Conclusions: Although other treatments were also administered to the patients and as a result data are difficult to interpret, it seems that the addition of CoPla improved pulmonary function., (Copyright: © 2020 Permanyer.)

Background: The treatment of patients with multiple myeloma (MM) has evolved in recent years, and the disease-associated prognosis has improved substantially. This improvement has been driven largely by the approval of novel agents, many of which are expensive and not universally available. Less expensive but effective approaches would be of value globally., Patients and Methods: All consecutive MM patients diagnosed in the Centro de Hematología y Medicina Interna de Puebla after 1993 were included in this study. Patients were given oral thalidomide (100 mg/day), oral dexamethasone (36-40 mg/week), and aspirin 100 mg/day. Bor-tezomib (1.75 mg s.c. every week) was administered to those who could afford it. After 4-6 weeks of treatment, patients were offered an outpatient-based hematopoietic cell transplant (HCT). After the recovery of granulocytes following HCT, patients continued indefinitely on thalidomide; those who failed to tolerate thalidomide were switched to lenalidomide (25 mg/day)., Results: The median overall survival (OS) for all patients has not been reached and is >157 months. Median follow-up of the patients lasted 14 months (range 1.3-157). The median OS of patients with and without HCT was similar. The response rate (complete remission or very good partial remission) was 72% for those given thalidomide plus dexamethasone versus 88% for those given bortezomib, thalidomide, and dexamethasone before HCT, but OS was not different. As post-HCT maintenance, 37 patients received thalidomide; 26 of those (70%) could be maintained indefinitely on thalidomide, whereas 11 were switched to lenalidomide after a median of 7 months; median OS of patients maintained on thalidomide or lenalidomide after HCT was not different., Conclusion: In this series, a regimen incorporating low-cost novel agents and outpatient HCT was associated with excellent long-term survival in the treatment of MM patients. This approach may be a model for MM treatment in underprivileged circumstances., (© 2020 S. Karger AG, Basel.)

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 out-patient 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 end-points 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'., (© 2019 British Society for Immunology.)

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 therapy-related 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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Thrombocytopenia (less than 100 × 10 9 /L platelets) presents in around one quarter of patients with nonalcoholic fatty liver disease (NAFLD), the hepatic component of insulin resistance (IR). It is unknown whether IR, by itself, associates with thrombocytopenia. Persons with NAFLD and/or IR were prospectively accrued in the study after February 2018. Insulin resistance was defined by assessing α hydroxybutyrate, lynoleoyl glycerolphosphocoline, oleic acid, and insulin (Quantose IR), whereas the presence of NAFLD was defined by serologic determinations (Fibromax) and liver transient elastography (Fibroscan). In 78 patients with NAFLD, thrombocytopenia was identified in 22 (28%), whereas in 19 persons with IR, 14 (73%) were found to have NAFLD. In persons with IR + NAFLD, thrombocytopenia presented in 9 (64%). In the subset of patients with IR, the prevalence of thrombocytopenia was 52%. There was only 1 patient with IR/without NAFLD who displayed thrombocytopenia. Significant statistical association between NAFLD and thrombocytopenia was found (odds ratio [OR]: = 13, confidence interval [CI]: 1.5-162, P = .05), whereas there was no association between IR and thrombocytopenia (OR = 0.38, CI: 0.06-2.3, P = .61). Insulin resistance, by itself, was not found to be associated with diminished platelet counts. The presence of NAFLD, one of the consequences of IR, seems to be required to lead into thrombocytopenia.

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.

Activated protein C resistance (aPCR) phenotypes represent around 20% of the laboratory findings in Mexican Mestizos having suffered thrombosis and displaying clinical markers of thrombophilia. In a single institution for a 276-month period, 96 Mexican mestizos with a history of thrombosis and clinical markers of a primary thrombophilic state were prospectively studied to identify a thrombophilic condition. An abnormal aPCR phenotype was identified in 18 individuals. Evaluation of those with an abnormal aPCR phenotype, identified that 44% had factor V Leiden mutation, 22% increased levels of factor VIII, 16% anti-phospholipid antibodies and 6% a lupus anticoagulant. In the remaining 22%, the use of direct oral anticoagulants (DOACs) in the past period of 12-24 h was recorded. We found significant associations between abnormal aPCR phenotype and the factor V Leiden mutation ( p  = 0022), between abnormal aPCR phenotype and the use of DOACs ( p  = 0.006) and between antiphospholipid antibodies and lupus anticoagulant ( p  < 0.0001). These data are consonant with those observed in other populations and further identify that consideration be given to identifying whether individuals are being treated with the novel DOACs when conducting laboratory studies oriented to identify the etiology of thrombosis.

Objective: Sticky platelet syndrome (SPS) is an inherited condition that leads to arterial and venous thrombosis. There is scant information about the association between SPS and obstetric complications. This study aimed to assess the relationship between SPS and fetal loss at a single institution., Materials and Methods: The obstetric histories of all consecutive female patients prospectively studied in a 324-month period at a single institution with a history of thrombosis and a clinical marker of primary thrombophilia were reviewed., Results: Between 1989 and 2016, 268 consecutive patients with a clinical marker of primary thrombophilia and a history of arterial or venous thrombosis were studied; of these, 108 were female patients. Within this subset of thrombophilic females, 77 (71%) had been pregnant at some point. Twenty-eight of these 77 patients (37%) had had a spontaneous abortion and 24 of those (86%) were found to have SPS. On the other hand, in a subset of 73 female patients with SPS who had been pregnant, 32% had miscarriages. These figures are significantly higher than the prevalence of spontaneous abortions in the general Mexican population of pregnant women, which is 12%-13% (chi-square: 7.47; p=0.0063). Accordingly, the relative risk of having a miscarriage is 2.66 times higher in female patients with SPS than in the general population (p=0.0014)., Conclusion: In Mexico, female patients with SPS experience significantly more spontaneous abortions than the general population. Since the treatment of SPS is simple and effective and could in turn prevent adverse obstetric outcomes, its investigation in women treated for obstetric complications may be useful and deserves further research.

Background: Using only serologic determinations, we have previously found that thrombocytopenia presents in less than one half of patients with non-alcoholic fatty liver disease (NAFLD)., Material and Methods: Employing a more accurate method to define the presence of NAFLD, serologic determinations (Fibromax®) coupled with liver transient elastography (TE/Fibroscan®), we have prospectively studied a group of 211 individuals with a suspicion of a liver disease., Results: NAFLD was identified in 81 individuals. In 48 persons another causes of liver damage were identified and discarded from further analysis. A subset of 33 patients with NAFLD without liver fibrosis or cirrhosis was analyzed. In eight of them (24%), thrombocytopenia (less than 150 × 10 9 /l platelets) was identified. The presence of thrombocytopenia in this subset of persons was associated with overweight, was usually mild, above 50 × 10 9 /l, was not associated to mucocutaneous bleeding and did not require treatment., Conclusions: NAFLD should be considered as a cause of mild thrombocytopenia. Our initial observation has been confirmed and defined more precisely. Additional studies are needed to further define more features of the thrombocytopenia of NAFLD, as well as its mechanisms.

Background: With the goal of achieving immune system reset, autologous hematopoietic stem cell transplantations have been performed in patients with multiple sclerosis (MS)., Material and Methods: Two hundred and eighty-six consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217., Results: One hundred and ninety-four females and 92 males were included; the median age was 47. All procedures were started on an outpatient basis and only 8 persons needed to be admitted to the hospital during the procedure. In order to obtain at least 1 × 106/kg viable CD34 cells, 1-4 aphereses were performed (median 1). The total number of viable CD34+ cells infused ranged between 1 and 19.2 × 106/kg (median 4.6). Patients recovered above 0.5 × 109/L absolute granulocytes on median day 8 (range 0-12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant-related deaths and the 128-month overall survival of the patients is 100%. In 82 persons followed up for 3 or more months, the Expanded Disability Status Scale diminished from a mean of 5.2-4.9, the best results being obtained in relapsing-remitting and primary progressive MS., Conclusions: It is possible to conduct autotransplants for patients with MS employing non-frozen PBSCs and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS., (© 2017 S. Karger AG, Basel.)