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The letter to the editor discusses the results of the VENICE-II trial, which evaluated the impact of venetoclax monotherapy on health-related quality of life (HRQoL) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). The trial showed significant improvements in HRQoL, with sustained benefits observed up to week 108. Venetoclax treatment also demonstrated positive outcomes in terms of response rates, duration of response, and overall survival. The safety profile of venetoclax remained consistent throughout the trial, with no new safety signals identified. The study emphasizes the importance of considering patient-centric factors, such as HRQoL, in CLL treatment decisions, especially in the context of evolving treatment options and long-term outcomes. [Extracted from the article]

High-dose melphalan (HD-Mel) has been successfully employed in autografting patients with multiple myeloma. An advantage of this regimen is that the total dose of Mel can be delivered in a single day, being particularly useful when non-frozen hematopoietic stem cells are employed in the autograft. All consecutive patients with R/R lymphomas, both HL and NHL studied and treated at two different centers were prospectively included in a study of ASCT employing a single dose of HD-Mel (200 mg/m2). A group of R/R HL or NHL autografted employing BEAM-like preparative regimens was constructed matched by diagnosis and age. The primary endpoint of the study was overall survival (OS), the secondary endpoint was event-free survival (EFS). Twenty-five R/R HL/NHL patients were prospectively accrued in the study. There were 8 (32%) females, 13 (52%) patients had at least 1 adverse effect: 7 (28%) developed mucositis, 5 (20%) neutropenic fever, and 6 (24%) grade IV nausea. In the HD-Mel group, median overall survival (OS) was not achieved and OS at 36 months was 71%, the transplant-related mortality being 0%. In the control group, median OS was not achieved and the 36-month OS was 76%, results not statistically significant (p 0.5). The EFS was also similar in both groups (p 0.5). HD-Mel alone is non-inferior to a BEAM-like regimen as a preparative regimen for autografting patients with R/R HL and NHL. The regimen is adequate to graft persons with non-frozen stem cells. [ABSTRACT FROM AUTHOR]

Venetoclax, a potent B-cell lymphoma-2 (BCL-2) inhibitor, has demonstrated clinical efficacy in chronic lymphocytic leukemia (CLL). VENICE II is an open-label, single-arm, phase 3b study (NCT02980731) evaluating the impact of venetoclax monotherapy (400 mg once daily) for ≤2 years on health-related quality of life (HRQoL) of patients with relapsed/refractory CLL. The primary endpoint was mean change in the global health status (GHS)/quality of life (QoL) subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) from baseline to Week 48. Overall, 210 patients received ≥1 dose of venetoclax; median treatment duration was 67.4 weeks. The primary endpoint was met with mean improvement of +9.3 points (n = 156, 95% confidence interval 6.1–12.5; p=.004) in GHS/QoL. At Week 48, clinically meaningful improvements were observed for role functioning, fatigue, and insomnia domains of EORTC QLQ-C30, suggesting venetoclax monotherapy has a positive impact on HRQoL. No new safety signals were reported. [ABSTRACT FROM AUTHOR]

To assess the concordance between lymphoma diagnoses made via tissue biopsy by local pathologists and also to assess the after review of these specimens by more specialized hematopathologists. A prospective, non-interventional and multicenter study was conducted at seven sites in Mexico from January 2017 to October 2017. Eligible biopsies were sampled from patients with a previous diagnosis of lymphoma on lymph node biopsy or a diagnosis of extranodal lymphoma, with adequate amount and tissue preservation for the review analysis. The biopsy tissues reviewed by local pathologists were also reviewed by hematopathologists participating in the study. The concordance in diagnosis results was classified into three categories: diagnostic agreement, minor discrepancy and major discrepancy. Out of 111 samples received, 105 samples met the eligibility criteria and were included for full analysis. The median patient age (range) was 54 (16–94) years. A diagnostic agreement was observed in 23 (21.9%) biopsies, minor discrepancies were observed in 32 (30.5%) biopsies and major discrepancies were observed in 50 (47.6%) biopsies. Diagnostic concordance varied across the seven study sites; the rate of major discrepancies ranged from 0% to 100% and the rate of diagnostic agreement ranged from 0% to 81.8%. Out of the 105 reviewed biopsies, a total of 89 cases were diagnosed as lymphoma by hematopathologists. This study showed that major discrepancies were observed following the review by hematopathologists compared with that of the local pathologist's initial diagnosis in nearly one-half cases. In addition, there was a wide variation in the percentage of diagnostic agreements and discrepancies among different study sites. [ABSTRACT FROM AUTHOR]

To describe chronic lymphocytic leukemia (CLL) treatment patterns and patient outcomes in Latin America. This chart review study (NCT02559583; 2008–2015)evaluated time to progression (TTP) and overall survival (OS) outcomes among patients with CLL who initiate done (n = 261) to two (n = 96) lines of therapy (LOT) since diagnosis. Differences in TTP and OS were assessed by Kaplan-Meier analysis, with a log-rank test for statistical significance. Association between therapeutic regimen and risk for disease progression or death was estimated using Cox proportional hazard regression. The most commonly prescribed therapies in both LOTs were chlorambucil-, followed by fludarabine- and cyclophosphamide (C)/CHOP-based therapies. Chlorambucil- and C/CHOP-based therapies were largely prescribed to elderly patients (≥65 years) while fludarabine-based therapy was predominantly used by younger patients (≤65 years). In LOT1, relative to chlorambucil-administered patients, those prescribed fludarabine-based therapies had lower risk of disease progression (hazard ratio [HR] and 95% confidence interval [CI] 0.32 [0.19–0.54]), whereas C/CHOP-prescribed patients had higher risk (HR 95%CI 1.88 [1.17–3.04]). Similar results were observed in LOT2. There was no difference in OS between treatments in both LOTs. Novel therapies such as kinase inhibitors were rarely prescribed in LOT1 or LOT2in Latin America. The greater TTP observed forfludarabine-based therapies could be attributed to the fact that fludarabine-based therapies are predominantly administered to young and healthy patients. Chlorambucil-based therapy, which has limited benefits, is frequently prescribed in Latin America. Prescribing novel agents for fludarabine-based therapy-ineligible patients with CLL is the need of the hour. Trial registration: ClinicalTrials.gov identifier: NCT02559583. [ABSTRACT FROM AUTHOR]

Introduction: Thrombotic thrombocytopenic purpura (TTP) is characterized by a reduction in the von Willebrand cleavage protein ADAMTS-13, mainly as a consequence of autoimmunity. Plasma exchange (PEx) is standard, achieving complete remission (CR) in 77-83% of cases, but rates are variable depending on ADAMTS-13 activity and relapse is frequent in patients with <10%. Thus, an effective frontline immunosuppressive treatment is needed. Materials and methods: We administered PEx daily until CR and rituximab 100 mg/dose/week for 4 consecutive weeks to 10 patients with a first TTP episode and 1 relapsed patient (8 females (72%) and 3 males (28%)). Median age was 34 years (15-46) and laboratory parameters at diagnosis were as follows: platelets 11 × 109/l (range 7-27.4 × 109/l), lactate dehydrogenase 1822 U/l (range 705-8220 U/l, normal 70-180 U/l), and haemoglobin 6 g/dl (range 4.2-11.8 g/dl). ADAMTS-13 activity was determined in eight patients and was <10% in all. ADAMTS-13 autoantibody titre was determined in seven patients and was >15 units/ml in all (ref: negative <12, undetermined 12-15, positive >15 units/ml); Shiga toxin was negative in all patients. The median number of PEx until CR was 7 (range 4-12); prednisone 1 mg/kg was administered to six patients. Results: The median follow-up was 22 months (range 4-49) and the estimated 2-year relapse-free survival was 89%; one HIV+ patient relapsed at 8 months follow-up. No complications related to PEx or rituximab were reported. Conclusions: Our study suggests that low-dose rituximab and PEx are effective as front-line treatment for acute TTP; however, a prospective trial is needed to demonstrate whether low-dose rituximab is as effective as the conventional dose. [ABSTRACT FROM AUTHOR]

Background Paroxysmal nocturnal haemoglobinuria (PNH) presents as two major entities: the classical form, predominantly haemolytic and a secondary type with marrow failure and resultant aplastic anaemia (AA-PNH). Currently, the treatment of choice of the haemolytic variant is eculizumab; however, the most frequent form of PNH in México is AA-PNH. Patients and methods Six consecutive AA-PNH patients with HLA-identical siblings were allografted in two institutions in México, employing a reduced-intensity conditioning regimen for stem cell transplantation (RIST) conducted on an outpatient basis. Results Median age of the patients was 37 years (range 25–48). The patients were given a median of 5.4 × 106/kg allogeneic CD34(+) cells, using 1–3 apheresis procedures. Median time to achieve above 0.5 × 109/l granulocytes was 21 days, whereas median time to achieve above 20 × 109/l platelets was 17 days. Five patients are alive for 330–3150 days (median 1437) after the allograft. The 3150-day overall survival is 83.3%, whereas median survival has not been reached, being above 3150 days. Conclusion We have shown that hypoplastic PNH patients can be allografted safely using RIST and that the long-term results are adequate, the cost–benefit ratio of this treatment being reasonable. Additional studies are needed to confirm the usefulness of RIST in the treatment of AA-PNH. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Imatinib has been considered as the gold standard for drug therapy of chronic myelogenous leukemia (CML) because it offers higher cytogenetic response and better quality of life than traditional drugs. In this study we applied the standard 400 mg dose of imatinib in 37 CML Ph (+) Mexican patients, monitoring their cytogenetic response using fluorescent in situ hybridization and carrying out molecular analyses using reverse transcription polymerase chain reaction. The study included 19 male and 18 female patients with a median age of 41 years. The median follow-up time from diagnosis was 56 months. Thirty-six patients (97%) achieved complete hematologic response in a median time of 29 days. Complete cytogenetic response and complete molecular remission was observed in only five (13%) and three (8.1%) patients, respectively, less than the expected rate (50-90%) reported in other studies. [ABSTRACT FROM AUTHOR]

Analyzes the features of the engraftment of allogeneic hematopoietic stem cells using reduced-intensity conditioning regimens. Correlation between number of infused mononuclear and CD34 cells; Median time to achievement of granulocytes in engrafted patients; Median time to recovery of platelets and neutrophils by patients who received CD34 cells.

Background: Essential thrombocythemia is a rare disease during childhood. Platelet morphological abnormalities are frequent and defects in platelet function tests, mainly hypoaggregation, occur. Materials and methods: An incidental diagnosis of essential thrombocythemia was established in a 9-year-old boy with a platelet count of 2050 × 10 9 /l. His platelets were studied for aggregation defects with four classical agonists employing optical aggregometry. Results: Aggregation ranged from 5% for adrenaline, 8% for collagen, 12% for ristocetin, to 25% with adenosine diphosphate, followed by complete disaggregation. Conclusion: Platelet refractoriness to classical agonists, probably compounded by platelet GPIb deficiency, was documented. The differential diagnosis is discussed. [ABSTRACT FROM AUTHOR]