Results of a completely outpatient autologous stem cell transplant program for lymphoma patients receiving reduced-intensity conditioning.

Autologous stem cell transplantation (ASCT) is commonly an in-patient procedure. However, outpatient ASCT grows as a cost-effective and feasible option for patients with lymphoma and reports assessing it after reduced-intensity conditioning (RIC) are sparse. We report the outcome of 102 patients with lymphoma who underwent ASCT on a full outpatient basis in a single-center transplant program between 2010 and 2020. Forty-two percent of the cohort required transfusion support, 36.3% experienced a neutropenic fever episode, 25.5% mucositis, and 9.8% developed severe infection. At a median time of 5 days (range 1-28), only 22.5% of the cohort required admission within the first 100 days after the autograft, median length of hospital stay was 0 days (range 0-14) and neutropenic fever was the most common reason for hospitalization. Non-relapse mortality at 1 year was 5%. ASCT in a completely outpatient setting is feasible, safe, and highly effective to treat lymphoma patients.

A high transfusion burden following an ambulatory-allogeneic hematopoietic cell transplantation using reduced-intensity conditioning is associated with adverse outcomes.

OBJECTIVES: Ambulatory allogeneic hematopoietic cell transplantation (allo-HCT) after reduced-intensity conditioning (RIC) is a cost-effective option for hematology patients. Data on the impact of transfusion burden in this setting are scarce; we analyzed this retrospectively. METHODS: A study of 177 HLA-identical and haploidentical allo-HCT recipients on an outpatient basis was conducted between 2013 and 2019. Packed red blood cell (PRBC) and platelet transfusions were documented from days 0-100 after HCT. RESULTS: A total of 121 patients (68.4%) required transfusion while 56 (31.6%) did not. In the multivariate analysis, a lower disease-free (DFS) and overall survival (OS) were documented for patients that received ≥9 total blood products (p = 0.018) (p = 0.014), those who required hospitalization (p = 0.001) (p < 0.001), had acute graft-versus-host disease (p = 0.016) (p = 0.004), and a high/very high Disease-Risk-Index (p = 0.002; p = 0.004), respectively. Transfusion of ≥5 PRBC units was associated with a lower OS (p = 0.027). The cumulative incidence of transplant-related mortality at two years for an HLA-identical transplant was 9.5% and for haploidentical, it was 27.1% (p = 0.027); this last group had significantly more transfusion demands than HLA-identical recipients (p = 0.029). CONCLUSION: Increased blood product utilization is an independent predictor of decreased survival in ambulatory RIC allo-HCT recipients. Further evidence leading to individualized guidelines to transfuse in this complex scenario is needed.

First case of Candida auris isolated from the bloodstream of a Mexican patient with serious gastrointestinal complications from severe endometriosis.

A 58-year-old woman was diagnosed with severe endometriosis and had multiple gastrointestinal tract complications for many years. Candida auris and C. parapsilosis were isolated from the bloodstream. Identification of C. auris was confirmed by amplification and sequencing of the internal transcriber spacer and the D1/D2 domain of the large rRNA gene subunit. Antifungal susceptibility was tested in both isolates using the Clinical Laboratory Standards Institute protocol M27-A3/S4. The patient evolved favorably with systemic antifungal therapy consisting of caspofungin and liposomal amphotericin B.

Treatment outcomes and chronicity predictors for primary immune thrombocytopenia: 10-year data from an academic center.

Primary immune thrombocytopenia (ITP) is an intriguing autoimmune disease characterized by autoantibodies against platelets and megakaryocytes. Clinical outcomes, response to treatment, and chronicity predictors were investigated. Patients with newly diagnosed primary ITP treated at a hematology referral center from 2008 to 2018 with complete medical and recent medication history were stratified by age as children < 16 years and adults > 16 years. Responses to treatment including steroids, splenectomy, rituximab, and eltrombopag were classified as response (R) and complete (CR). Factors for developing chronic ITP were determined by multiple regression with uni- and multivariate analysis. p < 0.05 was considered significant. A total of 175 patients were included, 52 children and 123 adults; women predominated with 57.7%. Response to first-line treatment in the whole cohort was 86.18%, CR 43.42% and R 42.76%. The initial response to steroids alone was 83.9% (n = 52/62), rituximab plus high-dose dexamethasone (HDD) 87.2% (n = 34/39), eltrombopag plus HDD 90.9% (n = 10/11), and children receiving IVIG alone 100% (n = 8/8); 9 children were under clinical observation and achieved spontaneous response; loss of response was documented in 15.21% children and 28.3% adults with a median time of 15.95 and 4.07 months respectively; 37.39% of adults and 30.76% of children progressed to a chronic course. Platelets ≥ 20 × 109/L and age ≥ 6 years were risk factors for chronic ITP in the univariate analysis in the adult and children groups, respectively. Clinical course and treatment outcomes for ITP are considerably heterogeneous. Higher platelet counts at diagnosis in adults and age ≥ 6 years in children were associated with an increased risk of chronicity.

IMPACT OF HLA-DPB1 MATCHING ON CLINICAL OUTCOMES AFTER HAPLOIDENTICAL-RELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION.

BACKGROUND: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. OBJECTIVE: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. METHODS: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. RESULTS: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. CONCLUSION: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Impact of hHLA-DPB1 matching on clinical outcomes after haploidentical-related hematopoietic stem cell transplantation

ABSTRACT Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Impact of Obesity on Lumbar Puncture Outcomes in Adults with Acute Lymphoblastic Leukemia and Lymphoma: Experience at an Academic Reference Center.

Background: Lumbar puncture (LP) is a hematology procedure that can require repeated attempts leading to traumatic LP (TLP), which has been related to the central nervous system (CNS) relapse. LP success can depend on the size and anatomy of the patient and the skill of the hematologist. The main objective was to determine the influence of body mass index (BMI) on LP outcomes. Materials and Methods: Adults with lymphoid malignancies requiring LP were included prospectively over one year; hematology residents performed most procedures. A 22-gauge Quincke needle was employed. Comparison between non-traumatic vs. traumatic LPs according to BMI, CNS relapse, and residents' year was performed. Results: Fifty-four patients with a mean age of 31.5±15.57 years were included. Diagnosis was Acute Lymphoblastic Leukemia-B (74%), Acute Lymphoblastic Leukemia-T (13%) and Non-Hodgkin Lymphoma (13%). 227 LPs were performed, 121 (53.3%) successful, 98 (43.2%) traumatic, 11 (11.2%) TLPs were macroscopically detectable and 87 (88%) microscopic; 8 (3.5%) were dry-taps. Median time between punctures was 11 days (1-202). Median BMI was 25 (22.8-39.6). Main indication for LP was prophylactic (74.5%); 39.2% were performed by first-year, 35.2% by second-year, 19.6% by third-year hematology residents. No difference (p = 0.145) for a TLP was found among residents. A BMI ≥30 (p = 0.040), non-palpable intervertebral space (p = 0.001) and more than one attempt (p = 0.001) were significant for TLP. TLP was not associated with CNS relapse (p = 0.962). Conclusion: Obesity predicted a TLP. A traumatic puncture did not increase the risk of CNS relapse at one-year follow-up.

Treatment of autoimmune hemolytic anemia: real world data from a reference center in Mexico.

BACKGROUND: Warm autoimmune hemolytic anemia (w-AIHA) is an uncommon disease with heterogeneous response to treatment. Steroids are the standard treatment at diagnosis, whereas rituximab has recently been recommended as the second-line therapy of choice. Our main objective was to document the response to treatment in patients with newly diagnosed w-AIHA, including the effectiveness of low-dose rituximab as frontline treatment and for refractory disease. METHODS: Patients with w-AIHA from 2002 to 2017 were included. Relapse-free survival (RFS), probability of maintained response (MR), and time-to-response were analyzed using the Kaplan-Meier method. Response was classified as complete, partial, and no response. RESULTS: We included 64 adults with w-AIHA (39 women and 25 men). The median age was 37 (16-77) years. Response rates to steroids alone were 76.7%, rituximab plus steroids, 100%; and cyclophosphamide, 80%. RFS with steroids at 6, 36, and 72 months was 86.3%, 65.1%, and 59.7%, respectively. Eighteen patients received rituximab at 100 mg/wk for 4 weeks plus high-dose dexamethasone as first-line therapy, with RFS at 6, 36, and 72 months of 92.3%, 58.7% and 44.1%, respectively. Eight patients refractory to several lines of therapy were treated with low-dose rituximab, and all achieved a response (three complete response and five partial response) at a median 16 days (95% confidence interval, 14.1-17.8), with a 75% probability of MR at 103 months; the mean MR was 81.93±18 months. CONCLUSION: Outcomes of w-AIHA treatment were considerably heterogeneous. Low rituximab doses plus high dexamethasone doses were effective for refractory disease.

Assessing the efficacy of an ambulatory peripheral blood hematopoietic stem cell transplant program using reduced intensity conditioning in a low-middle-income country.

Efficacy of an ambulatory hematopoietic stem cell transplant (HSCT) program with a reduced intensity conditioning regimen (RIC) in malignant hematological diseases was assessed. We analyzed 217 patients who underwent HSCT from August 2013 to July 2017. There were 78 (35.9%) HLA-identical, 56 (25.8%) haploidentical, and 83 (38.2%) autologous transplants. Two-year transplant-related mortality (TRM) for HLA-identical, haploidentical, and auto grafts were 20%, 25%, and 2.5%; relapse/progression was 44%, 60%, and 55%; overall survival (OS) was 61%, 44.8%, and 78.0%; and disease-free survival (DFS) was 36.8%, 26.5%, and 43.5%, respectively. Factors associated with a high risk of TRM were male sex (HR = 2.62, P = 0.031), fever and neutropenia (HR = 3.30, P = 0.023), and cell dose < 5 × 106 CD34 +/kg (HR = 4.24, P = 0.001); cGVHD was a protective factor for TRM (HR = 0.29, P = 0.022). Transfusion was associated with increased risk of relapse/progression in univariate and multivariate analysis (HR = 3.10, P = 0.001 and HR = 3.30, P = 0.004); cGVHD was a protective factor (HR = 0.18, P = 0.001 and HR = 0.17, P = 0.002). In a multivariate analysis for allo-HSCT, infections were associated with high risk of mortality (HR = 3.90, P = 0.016) and transfusion with reduced DFS (HR = 2.76, P = 0.029); for haplo-HSCT, CD34 + < 5 × 106/kg was a risk factor for mortality and lower DFS (HR = 5.41, P = 0.001 and HR = 3.93, P = 0.001). Outcomes of our RIC-based outpatient transplant program are comparable to excellence centers in high-income countries.

Evans syndrome: clinical perspectives, biological insights and treatment modalities.

Evans syndrome (ES) is a rare and chronic autoimmune disease characterized by autoimmune hemolytic anemia and immune thrombocytopenic purpura with a positive direct anti-human globulin test. It is classified as primary and secondary, with the frequency in patients with autoimmune hemolytic anemia being 37%-73%. It predominates in children, mainly due to primary immunodeficiencies or autoimmune lymphoproliferative syndrome. ES during pregnancy is associated with high fetal morbidity, including severe hemolysis and intracranial bleeding with neurological sequelae and death. The clinical presentation can include fatigue, pallor, jaundice and mucosal bleeding, with remissions and exacerbations during the person's lifetime, and acute manifestations as catastrophic bleeding and massive hemolysis. Recent molecular theories explaining the physiopathology of ES include deficiencies of CTLA-4, LRBA, TPP2 and a decreased CD4/CD8 ratio. As in other autoimmune cytopenias, there is no established evidence-based treatment and steroids are the first-line therapy, with intravenous immunoglobulin administered as a life-saving resource in cases of severe immune thrombocytopenic purpura manifestations. Second-line treatment for refractory ES includes rituximab, mofetil mycophenolate, cyclosporine, vincristine, azathioprine, sirolimus and thrombopoietin receptor agonists. In cases unresponsive to immunosuppressive agents, hematopoietic stem cell transplantation has been successful, although it is necessary to consider its potential serious adverse effects. In conclusion, ES is a disease with a heterogeneous course that remains challenging to patients and physicians, with prospective clinical trials needed to explore potential targeted therapy to achieve an improved long-term response or even a cure.