Impact of mother donor, peripheral blood stem cells and measurable residual disease on outcomes after haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in children with acute leukaemia.

Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II-IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.

On Temnocephala axenos Monticelli, 1898 (Platyhelminthes, Temnocephalida): taxonomic status and designation of a neotype.

Temnocephala axenos Monticelli, 1898 was described based on specimens from an unidentified host collected in Blumenau, Santa Catarina, Brazil. Information about type locality was imprecise and the host was later identified as Aegla laevis (Latreille, 1818). However, it is known that A. laevis is not present on the eastern side of the Andes. Also, only histological preparations from one specimen studied by Monticelli are currently available in the Museum für Naturkunde Berlin, but it showed none of the taxonomic characters needed for the characterization of the species. Although the updated description of the species based on Uruguayan specimens, neither the author nor the several previous studies about the species showed a search for the type material, a resolution for the misidentification of the type host or the imprecise type locality due to the subsequent geographical division of the municipality cited in the description. The Uruguayan specimens were not even geographically close to the type locality and a neotype was not designed to validate the species' taxonomic status again. Specimens from Santa Catarina and Paraná States, Brazil, were studied, as well as restudied Argentinean specimens. The new data were compared with the update description of the species. The historical background and the discussion about geographical origins and hosts of the species, as well as a designation of a neotype, allow comparative material of the type locality and type host to exist, eliminating doubts about the identification of T. axenos.

Importance of early absolute lymphocyte count after allogeneic stem cell transplantation: a retrospective study.

INTRODUCTION: Early lymphocyte recovery after allogeneic hematopoietic stem cell transplantation (HSCT) is related to the prevention of serious infections and the clearing of residual tumor cells. METHODS: We analyzed the absolute lymphocyte count at 20 (D+20) and 30 (D+30) days after HSCT in 100 patients with malignant hematologic diseases and correlated with the risk of transplant-related mortality, overall survival (OS), disease-free survival (DFS), nonrelapsed mortality (NRM), and risk of infection. RESULTS: Patients presenting with lymphocyte counts of <300 × 103/µL on D+30 have a 3.76 times greater risk of death in <100 days. Over a medium follow-up of 20 months OS, DFS, and NRM were similar between the groups. CONCLUSION: In our group of patients delayed lymphocyte recovery after HSCT was a predictor of early death post-HSCT.

Assessment of immature platelet fraction and immature reticulocyte fraction as predictors of engraftment after hematopoietic stem cell transplantation.

INTRODUCTION: Engraftment is a critical milestone of the hematopoietic stem cell transplantation (HSCT) process. The immature platelet fraction (IPF) and immature reticulocyte fraction (IRF) are considered early indicators of bone marrow recovery. The objective of this study was to assess these parameters as predictors of HSCT engraftment. METHODS: Neutrophil and platelet engraftment were defined as the first of three consecutive days with an absolute neutrophil count >0.5 × 10(9) /L or platelet count >20 × 10(9) /L, respectively. The IRF cutoff was 12%. Two IPF cutoffs were used: >6.2% and >10%. RESULTS: The study sample comprised 44 patients, of whom 24 had undergone autologous HSCT and 20 had undergone allogeneic HSCT. Absolute neutrophil counts >0.5 × 10(9) /L were preceded by IRF >12% in 86% of patients (38 of 44). Platelet counts >20 × 10(9) /L were preceded by an IPF >6.2% in 90% of patients (37 of 41) and by an IPF >10% in 63% of patients (26 of 41). CONCLUSION: The results show that IRF and IPF are engraftment predictors. Peak in IPF was observed before rise in platelet count, while IRF rises before absolute neutrophil count (ANC) and persists increased. This indicates that IRF and IPF can be considered as new tools for hematopoietic assessment after HSCT.

Patient socioeconomic status as a prognostic factor for allo-SCT.

The aim of the present study was to assess the influence of socioeconomic status (SeS) on the outcome of allo-SCT at a Brazilian SCT center. In total, 201 patients receiving HLA-identical related allo-SCTs were studied. The median age was 30 years. Overall, 163 patients had malignancies (CML 68, ALL/AML 63, myelodysplastic syndrome 12 and others 20). SeS was defined according to the Brazilian Association of Market Research Agencies classification, where people are clustered in groups A-E (richest to poorest). In total, 146 patients (72%) were classified as richest (A+B+C) and 55 (28%) as poorest (D+E). The D+E SeS group was associated with a higher incidence of chronic GVHD and acute GVHD (hazard ratio (HR)=2.61; P=0.001 and HR=2.62; P=0.001, respectively), better platelet and neutrophil engraftment (HR=1.94; P=<0.001 and HR=2.12; P=0.001) and with a higher TRM in multivariate analysis (HR=1.92; P=0.039). Estimated overall survival at 5 years was 55.2%. A D+E SeS (HR=2.13; P=0.001) was associated with a worse survival on multivariate analysis. In conclusion, a lower SeS is a strong prognostic factor in patients undergoing allo-SCT in Brazil, influencing engraftment, TRM and overall survival.

Prevalence of TEL/AML1 fusion gene in Brazilian pediatric patients with acute lymphoblastic leukemia.

We studied 58 childhood B-lineage acute lymphoblastic leukemia (B-ALL) in Brazilian sample patients at the time of diagnosis to investigate the prevalence of the cryptic t(12;21)(p13;q22). All bone marrow specimens were G-band karyotyped, and commercial dual-color DNA probes were used to search for fusion signals in nuclei. The karyotype analysis showed hyperdiploidy as the most frequent abnormality. The frequency of patients with TEL/AML1 gene fusion was 19% (11 out of 58 cases). Six of the positive samples had normal karyotypes. Deletion of the wild-type TEL allele was observed in 27.3% of TEL/AML1 fusion-positive cases, but it was also identified in 4.2% of the negative cases. Three cases presented two fusion signals, indicating possible duplication of the der(21). The mean age of the patients with TEL/AML1 fusion was 4.8 years and the mean amount of peripheral leukocytes was 44,270 x 10(6)/L. The higher frequency of females with B-ALL (33/58 cases) observed in our sample was probably due to the selection mode of the study cases. The prevalence of TEL/AML1 fusion in Brazilian children in our study is similar to that found in other populations.

Outcome of treatment in adult acute lymphoblastic leukemia in southern Brazil using a modified german multicenter acute lymphoblastic leukemia protocol.

Reports on treatment outcomes in adults with acute lymphoblastic leukemia (ALL) in Brazil are sparse. To evaluate the outcome of patients with ALL managed by the public healthcare system, we studied 42 adults treated from 1990 to 1997 in the Division of Hematology at Hospital de Clínicas, Porto Alegre, Brazil. Of these patients, 14/42 were females and their median age at diagnosis was 26 (17-64) years. The diagnosis of ALL was based on cytological examination of marrow smears, and immunophenotypic and cytogenetic studies, when available. Fifty percent of the patients expressed CD10, 30% were CD10 negative and CD19 positive and 20% expressed T markers. Philadelphia chromosome was found in 4 (7.14%). The chemotherapy protocol was adapted from the German Multicenter ALL (GMALL) 02-84 protocol. The complete remission rate was 93% and the overall survival at 5 years was 41%. No particular risk factor was identified in our series. These results are comparable to the findings of other international studies.

Emotional and behavioral symptoms in children with acute leukemia.

BACKGROUND AND OBJECTIVES: The diagnosis of leukemia is probably one of the most severe stressors that children can experience and may be associated with emotional and behavioral symptoms indicating comorbidity with mental health disorders. This study aims to evaluate the presence of emotional and behavioral symptoms in children with acute leukemia exposed to chemotherapy from outpatient services at two university hospitals in Brazil. DESIGN AND METHODS: In this cross-sectional study, emotional and behavioral symptoms were assessed using the Children Behavior Checklist (CBCL) in three groups of children aged 5-14 years: a) children with acute leukemia (n = 21); b) children with blood dyscrasias (n = 21); c) children evaluated or treated in a pediatric outpatient service (n = 33). RESULTS: Children with blood dyscrasias had significantly few symptoms of externalization (delinquent and aggressive behavior) than pediatric controls (p< 0.05). Children with leukemia did not differ from the two other groups regarding symptoms of externalization. No significant difference on the scores of the CBCL internalization dimension (anxiety, depression, somatic symptoms and withdrawn) was found among the three groups. INTERPRETATION AND CONCLUSIONS: These findings seem to indicate that children with acute leukemia do not have more emotional or behavioral symptoms than children with benign hematologic or physical diseases suggesting that comorbidity with mental disorders is not higher in children with acute leukemia than in children in the other two groups.