There is limited data about the long-term treatment outcome and prognosis of childhood acute lymphoblastic leukemia (ALL) in developing countries. Our study was designed to assess survival data and identify risk factors. Data of 142 children with ALL who were treated with a modified BFM 95 protocol between 1997 and 2007 were evaluated. The median age was 4.3 years. Complete remission (CR) rate after induction phase was 93.5%; with 2.1% induction-related mortality and 0.7% having resistance disease. Of complete responders, 67.1% are in continuous CR with a median follow-up of 63 months (range: 24 to 153 mo). Treatment-related mortality was 17.7% and the total rate of treatment abandonment was 3.5%. The probability of event-free survival was 67.3% (95% confidence interval 59.3-75.3) at 4 years and 63.2% (95% confidence interval 54.4-72.0) at 8 years. This report examines children with ALL treated with a modified ALL-BFM 95 protocol in a tertiary care center in Turkey with adequate follow up and demonstrates the need for improvements especially for patients with unfavorable risk group and strategies to reduce deaths from infection in CR to keep pace with cure rates in developed countries.
Abstract Objective The selection of graft‐vs. ‐host disease (GvHD) prophylaxis is vital for the success of hematopoetic stem cell transplantation (HSCT), and calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. The aim of this study is to analyze the results of switching cyclosporine (CSA) to tacrolimus because of acute GvHD, engraftment syndrome (ES), persistent low level of CSA, or various CSA‐associated adverse events in the first 100 days of pediatric HSCT. Materials and Methods This is a retrospective analysis of 192 patients who underwent allogeneic hematopoietic stem cell transplantation at Medicalpark Göztepe and Antalya Hospitals between April 2014 and May 2019 had therapy switched from CSA to tacrolimus‐based immunosuppression within 100 days of transplant. Results The reasons for conversion to tacrolimus were low level of CSA ( n = 70), aGvHD ( n = 63), CSA‐associated neurotoxicity ( n = 15), CSA‐associated nephrotoxicity ( n = 10), hypertension ( n = 10), allergic reactions ( n = 9), ES ( n = 7), CSA‐associated hepatotoxicity ( n = 5), and vomiting ( n = 3). The median day after transplant for conversion to tacrolimus for all patients was day 20 (range 0‐100 days). Response rates to conversion were 38% for GvHD, 86% for neurotoxicity, 50% for nephrotoxicity, 60% for hepatotoxicity, 80% for hypertension, 66% for vomiting, and 57% for ES. Twenty‐nine patients (15%) experienced tacrolimus‐associated toxicities after therapy conversion to tacrolimus. Neurotoxicity emerged as posterior reversible encephalopathy syndrome (PRES), which was the most common toxicity observed after conversion (18/29 patients). Conclusion Our data support the quick conversion to tacrolimus in the condition of persistent low CSA levels with acceptable efficacy and safety. Although both drugs are CNI and share a very similar mechanism of action, the conversion could be preferred especially in specific organ toxicities with special attention for neurotoxicity after conversion.
Background: Although, regular red cell transfusion and advanced iron chelation therapy alternatives have improved life expectancy, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with beta thalassemia major. However, the availability of HLA-matched related donor remains the main obstacle for allogenic HSCT. A few promising studies have been reported but experience with HLA matched unrelated donors is limited. Here, we present the result of 51 children with beta thalassemia major who received allogeneic HSCT from HLA-matched unrelated donors. Patients and methods: We retrospectively assessed 51 unrelated HSCT in children with beta thalassemia major. All patients received busulphan (BU) based myeloablative conditioning regimen. Busulphan was used according to weight adjusted dose and cumulative AUC of 85-90 mg/Lxh. In addition, all patients received fludarabine 150 mg/m2 in five days, cylophosphamide 120 mg/kg in 3 days, thio-tepa 10 mg/kg and ATG 30 mg/kg in 3 days. Cyclosporin-A and MTX were used for graft versus host disease (GVHD) prophylaxis. Donor chimerism was evaluated in either bone marrow or peripheral blood on days +30, +100 and +180. Results: The median age of the patients was 87 months (range 14-184 month). Two of patients were Class I and 49 of them Class II. The median serum ferritin level was 1.277 ng/ml (range, 425-5832). All of the donors were 10/10 matched with HLA high resolution in GVHD direction but 9 of them 9/10 matched in graft failure direction. Thirty-four of them received BM (median TNC: 6.6 × 108, range; 1.62-17.60) and 17 PBSC (median MNC: 7.05 × 108, range; 5.0-13.0) with median CD34+ cell number 7.23 × 106 (range 1.54-15.70). The median neutrophil and platelet engraftment days were 14 and 18 days in PBSC and 17 and 23 days in BM group, respectively. Grade I-IV acute GVHD was observed in 11 patients (22%), six of which experienced Grade II-IV (12%). Chronic GVHD was not observed. Moderate VOD was seen in 15 patients (29%) and treated with defibrotide successfully. We lost one patient because of sepsis on post-transplant day 124. Graft failure was experienced in one and graft rejection in 2 patients. All the other patients are alive with full donor chimerism (between 95.47-100%) with a median 14 months (range 3-46 months) follow up. Probability of thalassemia-free (TFS) and overall survival (OS) were found 92% and 98%, respectively. Discussion and conclusion: These data shown that the results of HSCT from unrelated donors in selected low risk thalassemia patients (Class I & II) may comparable to HSCT from matched sibling donors. We believe that having a fully matched donor is an important role in successful outcomes in patients who underwent unrelated stem cell transplantation. However, it needs further studies with long term follow up and larger study population.
The randomized comparison of deferasirox to deferoxamine for myocardial iron removal in patients with transfusion-dependent anemias (CORDELIA) gave the opportunity to assess relative prevalence and body distribution of iron overload in screened patients.Patients aged ≥ 10 yr with transfusion-dependent anemias from 11 countries were screened. Data were summarized descriptively, overall and across regions.Among 925 patients (99.1% with β-thalassemia major; 98.5% receiving prior chelation; mean age 19.2 yr), 36.7% had myocardial iron overload (myocardial T2* ≤ 20 ms), 12.1% had low left ventricular ejection fraction. Liver iron concentration (LIC) (mean 25.8 mg Fe/g dw) and serum ferritin (median 3702 ng/mL) were high. Fewer patients in the Middle East (ME; 28.5%) had myocardial T2* ≤ 20 ms vs. patients in the West (45.9%) and Far East (FE, 40.9%). Patients in the West had highest myocardial iron burden, but lowest LIC (26.9% with LIC < 7 mg Fe/g dw) and serum ferritin. Among patients with normal myocardial iron, a higher proportion of patients from the ME and FE had LIC ≥ 15 than < 7 mg Fe/g dw (ME, 56.7% vs. 17.2%; FE, 78.6% vs. 7.8%, respectively), a trend which was less evident in the West (44.6% vs. 33.9%, respectively). Transfusion and chelation practices differed between regions.Evidence of substantial myocardial and liver iron burden across regions revealed a need for optimization of effective, convenient iron chelation regimens. Significant regional variation exists in myocardial and liver iron loading that are not well explained; improved understanding of factors contributing to differences in body iron distribution may be of clinical benefit.
beta-thalassemia, an anemic genetic disorder, remains a significant global health issue, especially in the era of globalization where healthcare, economics, and education are more tightly interconnected. Although previous studies focused on the medical aspect of beta-thalassemia and the affects of consanguineous marriages, we investigated what affects the socio-economic geography of beta-thalassemia and how it affects the spread rate using self-organizing maps (SOM) and Sammon mapping. We converted data generated from questionnaires into numerical variables to facilitate the subsequent analysis of how certain variables contribute to beta-thalassemia's spread. We expected a strong correlation among variables (current education and financial status, information availability, neighborhood prevention programs, and treatment affordability). Only 28% of the population contained both high education and high income, thus had the highest awareness. We studied the mapped data and identified relevant variables corresponding to factors affecting the spread rate of beta-thalassemia. We concluded that education directly correlates to beta-thalassemia's spread rate. Education created a ripple effect, affecting other variables. The data supports the idea that a more educated population, combined with aggressive prevention and treatment programs should prevent the spread of beta-thalassemia.
BackgroundInfections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed.MethodsWe performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints.Findings1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2–26.0) and 11.2% (9.6–13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2–3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3–68.9] vs. 70.4 [67.9–72.8]; multivariate HR 1.5 [1.1–2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8–77.4] vs. 79.0% [76.7–81.1]; multivariate HR 1.7 [1.1–2.5]; p = 0.01).InterpretationPre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure.FundingThere was no external funding source for this study.
