Long-Term Outcomes of Childhood Acute Lymphocytic Leukemia Treated with Adapted Berlin-Frankfurt-Münster (BFM) Protocols: A Multicentric Analysis from a Developing Country.

INTRODUCTION: The objective of the current study was to determine the survival probabilities of children and adolescents with acute lymphocytic leukemia treated with adapted Berlin-Frankfurt-Münster (BFM) protocols and compare our results with the original BFM reports. METHODS: This retrospective study included 695 patients up to 19 years old treated with adapted BFM protocols between 1997 and 2018 in four hospitals in Rio de Janeiro. The 1997-2007 and 2008-2018 cohorts were analyzed separately. RESULTS: More than half of the patients were stratified into the high-risk BFM classification. Overall and event-free survivals were, in the 1997-2007 period, respectively, 88% and 80% (BFM standard risk group-SRG), 75% and 67% (intermediate risk group-IRG), and 48% and 33% (high-risk group-HRG). The corresponding numbers for the 2008-2018 period were 93% and 84% (SRG), 75% and 63% (IRG), and 64% and 57% (HRG). In the second period, both the OS (HR = 0.71, p = 0.011) and EFS (HR = 0.62, p < 0.001) were higher. Except for the intermediate-risk group, the latter results are comparable to the BFM. CONCLUSION: The BFM protocol adaptations can be safely implemented in developing countries, accounting for local specificities.

Acute promyelocytic leukemia in a long-standing HIV-positive patient: Case report and literature review.

The use of antiretroviral therapy has drastically improved the life quality and prognosis of people living with the human immunodeficiency virus (HIV). The risk of acute myeloid leukemia (AML) currently does not appear to be significantly increased compared to the general population. Acute promyelocytic leukemia (APL), infrequent in people with HIV, is a distinct subtype of AML with unique molecular pathogenesis, clinical manifestations, and treatment. Herein we describe a fatal case of APL hypogranular variant in an HIV-positive patient presenting with hyperleukocytosis. Also, we conducted a literature review of the ten cases reported so far.

Monosomy 7 in donor cell-derived leukemia after bone marrow transplantation for severe aplastic anemia: Report of a new case and review of the literature.

Monosomy 7 arises as a recurrent chromosome aberration in donor cell leukemia after hematopoietic stem cell transplantation. We report a new case of donor cell leukemia with monosomy 7 following HLA-identical allogenic bone marrow transplantation for severe aplastic anemia (SAA). The male patient received a bone marrow graft from his sister, and monosomy 7 was detected only in the XX donor cells, 34 months after transplantation. The patient's bone marrow microenvironment may have played a role in the leukemic transformation of the donor hematopoietic cells.

Mesenchymal stromal cells impair the differentiation of CD14(++) CD16(-) CD64(+) classical monocytes into CD14(++) CD16(+) CD64(++) activate monocytes.

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) possess immunomodulatory activity both in vitro and in vivo. However, little information is available regarding their function during the initiation of immunologic responses through their interactions with monocytes. While many studies have shown that MSC impair the differentiation of monocytes into dendritic cells and macrophages, there are few articles showing the interaction between MSC and monocytes and none of them has addressed the question of monocyte subset modulation. METHODS: To understand better the mechanism behind the benefit of MSC infusion for graft-versus-host treatment through monocyte involvement, we performed mixed leucocyte reactions (MLR) in the presence and absence of MSC. After 3 and 7 days, cultures were analyzed by flow cytometry using different approaches. RESULTS: MSC induced changes in monocyte phenotype in an MLR. This alteration was accompanied by an increase in monocyte counting and CD14 expression. MSC induced monocyte alterations even without contact, although the parameters above were more pronounced with cell-cell contact. Moreover, the presence of MSC impaired major histocompatibility complex (MHC) I and II, CD11c and CCR5 expression and induced CD14 and CD64 expression on monocytes. These alterations were accompanied by a decrease in interleukin (IL)-1ß and IL-6 production by these monocytes, but no change was observed taking into account the phagocytosis capacity of these monocytes. CONCLUSIONS: Our results suggest that MSC impair the differentiation of CD14(++) CD16(-) CD64(+) classical monocytes into CD14(++) CD16(+) CD64(++) activated monocytes, having an even earlier role than the differentiation of monocytes into dendritic cells and macrophages.

Rhodamine 123 efflux in human subpopulations of hematopoietic stem cells: comparison between bone marrow, umbilical cord blood and mobilized peripheral blood CD34+ cells.

Hematopoietic stem cells (HSC) can be identified by the expression of the CD34 molecule. CD34+ cells are found in bone marrow (BM), umbilical cord blood (UCB) and in mobilized peripheral blood (PB). CD34+ cells express P-glycoprotein (Pgp), a product of the multidrug resistance (MDR) gene. Pgp activity can be measured by the efflux of the dye Rhodamine 123 (Rho 123) and can be blocked by verapamil. Transport activity in HSC suggests that Pgp could have a functional role in stem cell differentiation. This study compared the number of CD34+ cells with Pgp activity measured by efflux of Rho 123 in the hematopoietic population obtained from different sources. Samples were analysed for their content of CD34+ cells, and BM had a significantly higher amount of CD34+ cells compared to UCB, mobilized PB and normal PB. When the frequency of Rholow cells was studied among the CD34+ population, an enrichment of cells with Pgp activity was observed. The frequency in BM was significantly lower than that in UCB and mobilized PB. The low retention of Rho 123 could be modified by verapamil, indicating that the measurements reflected dye efflux due to Pgp activity. Although UCB and mobilized PB had a lower number of CD34+ cells compared to BM, the total number of CD34+ cells with Pgp activity was similar in the three tissues. The different profiles may indicate the existence of subpopulations of stem cells or different stages of cellular differentiation detected by the extrusion of the dye Rho 123.