Evaluation of efficacy and safety in the use of cytarabine for mobilization of hematopoietic stem cells in a reference hospital in northeastern Brazil.

Autologous hematopoietic stem cell transplantation (Auto-HSCT) is widely used in the treatment of patients with hematological neoplasms. Since these cells circulate in small quantities in the periphery, the use of regimens that promote their mobilization is essential. In this study, we retrospectively evaluated the efficacy and safety of using intermediate doses of cytarabine (1.6 g/m²) + filgrastim (10 mcg/kg/day) in the mobilization of stem cells in 157 patients treated by the Unified Health System at the Hematology and Bone Marrow Transplant Service of the Hospital Real Português de Beneficência, in Recife, Pernambuco. The sample included patients with multiple myeloma (MM) (58.6 %), lymphomas (29.9 %), and other neoplasms (11.5 %). The target of 2.0 × 10 6 CD34+ cells/kg was achieved by 148 (94.3 %) patients, in most cases (84.1 %) in a single apheresis and the median number of cells collected was 9.5 × 10 6 CD34+ cells/kg. No episode of febrile neutropenia was observed, however, 79 patients (50.3 %) required platelet transfusion (no cases attributed to bleeding). The median engraftment time was 11 days. Given these results, we suggest that the use of intermediate doses of cytarabine, combined with filgrastim, is safe and effective in mobilizing hematopoietic stem cells (HSCs).

Lethal destructive sinusopathy due to amphotericin B-resistant Aspergillus flavus: A case report.

BACKGROUND: The prevalence of pulmonary aspergillosis and the importance of its early diagnosis are recognized. However, non-pulmonary involvement, including the sinuses region, is not frequently reported, and an infection in this area can affect all paranasal sinuses (pansinusopathy), being a rare pathology that affects immunocompromised hosts. Recent studies have highlighted the occurrence of Aspergillus flavus resistant to antifungal therapy. Therefore, a nasal sinus infection by resistant Aspergillus strains in immunocompromised patients may be linked to a high risk of lethality. CASE REPORT: We are reporting a resistant A. flavus infection in an allogeneic hematopoietic stem cell transplant recipient with episodes of febrile neutropenia, and prolonged use of various antibacterial drugs and antifungal prophylaxis. The patient underwent brain magnetic resonance, which showed the presence of pansinusopathy, and presented necrosis in the left nasal region. Direct microscopic examination of a sample taken from the nasal mucosa revealed the presence of septate hyphae and conidiophores resembling those of A. flavus, that species being the identification achieved with MALDI-TOF MS. Antifungigram was performed by microdilution in broth (EUCAST-E.DEF. 9.3.2) and E-test, and resistance to amphotericin B was shown in both tests. The patient died after septic shock and hemorrhage. CONCLUSIONS: Invasive fungal infections due to amphotericin-B resistant A. flavus may lead to the death of the patient due to an ineffective therapeutic management. Therefore, antifungal susceptibility testing are of utmost importance for administering the proper treatment.

Lethal destructive sinusopathy due to amphotericin B-resistant Aspergillus flavus: A case report

Background:The prevalence of pulmonary aspergillosis and the importance of its early diagnosis are recognized. However, non-pulmonary involvement, including the sinuses region, is not frequently reported, and an infection in this area can affect all paranasal sinuses (pansinusopathy), being a rare pathology that affects immunocompromised hosts. Recent studies have highlighted the occurrence of Aspergillus flavus resistant to antifungal therapy. Therefore, a nasal sinus infection by resistant Aspergillus strains in immunocompromised patients may be linked to a high risk of lethality.Case report:We are reporting a resistant A. flavus infection in an allogeneic hematopoietic stem cell transplant recipient with episodes of febrile neutropenia, and prolonged use of various antibacterial drugs and antifungal prophylaxis. The patient underwent brain magnetic resonance, which showed the presence of pansinusopathy, and presented necrosis in the left nasal region. Direct microscopic examination of a sample taken from the nasal mucosa revealed the presence of septate hyphae and conidiophores resembling those of A. flavus, that species being the identification achieved with MALDI-TOF MS. Antifungigram was performed by microdilution in broth (EUCAST-E.DEF. 9.3.2) and E-test, and resistance to amphotericin B was shown in both tests. The patient died after septic shock and hemorrhage.Conclusions:Invasive fungal infections due to amphotericin-B resistant A. flavus may lead to the death of the patient due to an ineffective therapeutic management. Therefore, antifungal susceptibility testing are of utmost importance for administering the proper treatment. (AU)

Antecedentes:La prevalencia de la aspergilosis pulmonar y la importancia de su diagnóstico precoz son ampliamente conocidos; sin embargo, la afectación extrapulmonar no se informa con frecuencia y son pocos los casos documentados de infección de los senos nasales. Una infección en esta área puede alcanzar todos los senos paranasales (pansinusopatía) cuando afecta a pacientes inmunodeprimidos, lo que agrava la enfermedad preexistente. Estudios recientes han destacado la aparición de cepas que muestran resistencia al tratamiento con fármacos antimicóticos. En el paciente inmunodeprimido una infección de los senos nasales por una cepa de Aspergillus resistente implica un alto riesgo de letalidad.Caso clínico:Presentamos un caso de infección por Aspergillus flavus resistente en un receptor de trasplante alogénico de células madre hematopoyéticas, con episodios de neutropenia febril y uso prolongado de diversos fármacos antibacterianos, además de profilaxis antifúngica. Se realizó una resonancia magnética cerebral que reveló la existencia de pansinusopatía con necrosis en la región nasal izquierda. En el examen microscópico directo de la mucosa nasal se observaron hifas tabicadas y la presencia de conidioforos compatibles con Aspergillus flavus; la identificación con el método MALDI-TOF MS arrojó la especie mencionada. El antifungigrama fue realizado por el método de microdilución en caldo (EUCAST-E.DEF. 9.3.2) y E-test; con ambas técnicas el aislamiento mostró resistencia a la anfotericina B. El paciente falleció tras un shock séptico y hemorragia.Conclusiones:Las infecciones fúngicas invasivas por cepas de Aspergillus flavus resistentes a la anfotericina B puede derivar en la muerte del paciente debido a la ineficacia del tratamiento antifúngico. Es por ello que las pruebas de sensibilidad a los antifúngicos son de suma importancia para establecer así el tratamiento correcto. (AU)

Impact of CD34 Cell Dose and Conditioning Regimen on Outcomes after Haploidentical Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Relapsed/Refractory Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a life-threatening disease that can be cured with allogeneic cell transplantation (HCT). Haploidentical donor transplantation with post-transplantation cyclophosphamide (haplo-PTCy) is an option for patients lacking an HLA-matched donor. We analyzed 87 patients who underwent haplo-PTCy between 2010 and 2019. The median patient age was 14 years (range, 1 to 69 years), most were heavily transfused, and all received previous immunosuppression (25% without antithymocyte globulin). Almost two-thirds (63%) received standard fludarabine (Flu)/cyclophosphamide (Cy) 29/total body irradiation (TBI) 200 cGy conditioning, and the remaining patients received an augmented conditioning: Flu/Cy29/TBI 300-400 (16%), Flu/Cy50/TBI 200 (10%), or Flu/Cy50/TBI 400 (10%). All patients received PTCy-based graft-versus-host disease (GVHD) prophylaxis. Most grafts (93%) were bone marrow (BM). The median duration of follow-up was 2 years and 2 months. The median time to neutrophil recovery was 17 days. Primary graft failure occurred in 15% of the patients, and secondary or poor graft function occurred in 5%. The incidences of grade II-IV acute GVHD was 14%, and that of chronic GVHD was 9%. Two-year overall survival and event-free survival (EFS) were 79% and 70%, respectively. EFS was higher for patients who received augmented Flu/Cy/TBI (hazard ratio [HR], .28; P = .02), and those who received higher BM CD34 cell doses (>3.2 × 10E6/kg) (HR, .29; P = .004). The presence of donor-specific antibodies before HSCT was associated with lower EFS (HR, 3.92; P = .01). Graft failure (HR, 7.20; P < .0001) was associated with an elevated risk of death. Cytomegalovirus reactivation was frequent (62%). Haploidentical HCT for SAA is a feasible procedure; outcomes are improved with augmented conditioning regimens and BM grafts with higher CD34 cell doses.

Hematopoietic cell transplantation for Diamond Blackfan anemia: A report from the Pediatric Group of the Brazilian Bone Marrow Transplantation Society.

OBJECTIVES: The aim of this study was to analyze the outcomes of children with Diamond-Blackfan anemia (DBA) treated in Brazil with hematopoietic cell transplantation (HCT). METHODS: We performed a retrospective analysis of 44 pediatrics patients transplanted between 1990 and 2018. The median age of patients was 5 years, and 57% were male. Twenty-five received their first HCT from an HLA-matched sibling donor (MSD), 12 from a HLA matched unrelated bone marrow donor (MUD 10/10, n = 12) and 7 other HLA mismatched donors (MMD). RESULTS: After a median follow-up of 4 years, estimate 5-year overall survival (OS) for the entire cohort was 70%, 80% for MSD group, 73% for MUD, and 29% for MMD. Thirty-eight out of the 44 evaluable patients engrafted successfully. Primary and secondary graft failure was observed in five and three patients, respectively. Rates of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 25% and 18%, respectively. Nine patients developed chronic GVHD (cGVHD). CONCLUSION: Overall survival rates observed after HLA matched donors transplant for DBA were comparable to those reported from higher-income countries and international registries.

Impact of Treatment Prior to Allogeneic Transplantation of Hematopoietic Stem Cells in Patients with Myelodysplastic Syndrome: Results of the Latin American Bone Marrow Transplant Registry.

It has been suggested that bridging therapy with intensive chemotherapy and/or hypomethylating agents followed by hematopoietic stem cell transplantation (HSCT) can be valuable in the treatment of patients with myelodysplastic syndromes (MDS). However, the influence of this approach on HSCT outcomes remains poorly defined. Therefore, our objective was to investigate the influence of treatment before HSCT in patients with MDS. We retrospectively analyzed data from the Latin American registry of 258 patients from 17 Latin American centers who underwent HSCT from 1988 to 2019. Our data showed that there was pre-HSCT. We detected no significant difference regarding the impact on overall survival of treated and untreated patients before HSCT. Despite these data, the type of previous treatment among treated patients showed a significant difference in overall survival. Treatment with hypomethylating agents together with pre-HSCT chemotherapy seems to result in better survival of the studied population. These data correspond to the first results obtained through cooperative work between various centers in Latin America comparing the different approaches to patients and reflecting their reality and challenges. Therefore, the selection of pretransplant bridge therapy should be analyzed and focus given primarily to those approaches that result in better survival of patients with MDS.

Allogeneic Bone Marrow Transplants for Pediatric Severe Aplastic Anemia: Real-world Data comparing Matched Related and Unrelated Donors in a Developing Country. Retrospective study on behalf of the Pediatric Hematopoietic Stem Cell Transplant Working Group of the Brazilian Bone Marrow Transplantation Society (SBTMO) and the Brazil-Seattle Consortium (Gedeco).

In this study, we report on major MRD or URD BMT outcomes in pediatric patients with SAA in Brazil. This was a retrospective study, which included 106 patients ≤18 years old who received a first BMT for SAA. All patients received bone marrow as graft source from an MRD (n = 69) or a URD (n = 37). Conditioning regimen was non-myeloablative in 73.6% of cases, and GVHD prophylaxis comprised a calcineurin inhibitor plus methotrexate in 89.6% of patients. After a median follow-up of 4.5 years after BMT, 81 patients are alive, with a 4-year OS of 77% and no statistically significant difference between the MRD and URD groups (82% vs. 69%, respectively; P = .08). Grade III-IV aGVHD at 6 months and cGVHD at 2 years were observed in 8% and 14% of cases, respectively, and were not statistically different between the groups. Twenty-five (23%) patients died at a median of 2.9 months after BMT. Our study showed that 4-year OS after BMT was not statistically different between MRD and URD recipients. This study shows that the outcomes of pediatric patients transplanted for SAA with a URD in Brazil are approaching those of MRD transplants. In contrast, OS after MRD BMT was lower than we would expect based on previous reports. The wide range of preparatory regimens used by the study centers highlights the need for standardized protocols for these children. Our findings provide a benchmark for future studies focused on improving BMT outcomes in this setting in Brazil.

Successful nonmyeloablative allogeneic stem cell transplantation for therapy-related acute myelogenous leukemia in a patient with preexisting visceral fungal infection.

Therapy-related acute myelogenous leukemia (t-AML) is a generally fatal disease with a very poor response to conventional chemotherapy. Allogeneic stem cell transplantation (allo-SCT) has been reported in patients with chemotherapy- responsive t-AML. However its use is limited owing to complications from previous treatments. Nonmyeloablative conditioning provides rapid hematologic engraftment and it is a feasible option for patients who are at increased risk for conventional SCT. There are few data on their use in patients with t-AML. We describe the case of a boy who developed visceral fungal infection with liver abscesses after induction chemotherapy for t-AML. He received allo-SCT with a nonmyeloablative regimen, plus amphotericin B during the transplant procedure. The patient is alive and free of both leukemia and fungal infection 2 years after allo-SCT. Nonmyeloablative allo-SCT may provide durable remission in patients with t-AML, preexisting invasive fungal infections, and a high risk of adverse effects from standard chemotherapy and prolonged cytopenia, without resurgence of the fungal infection.

Prospective trial of mycophenolate mofetil-cyclosporine A prophylaxis for acute GVHD after G-CSF stimulated allogeneic bone marrow transplantation with HLA-identical sibling donors in patients with severe aplastic anemia and hematological malignancies.

The combination of methotrexate and cyclosporine A (MTX-CSA) is the standard regimen for the prevention of graft vs. host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) from HLA-identical siblings. Mycophenolate mofetil and CSA (MMF-CSA) combination has been successfully used for GVHD prophylaxis after non-reduced intensity conditioning (non-RIC) allo-SCT with peripheral blood or non-G-CSF stimulated bone marrow as stem cell source. We report the results of the first prospective trial of the MMF-CSA combination for acute GVHD prophylaxis in 47 patients after non-RIC G-CSF stimulated allo-BMT (G-BMT) from HLA-identical siblings in patients with severe aplastic anemia (SAA) or hematological malignancies. Median age was 28 yr (range, 6-48 yr). Median follow-up was 22 months. The median time to neutrophil and platelets recovery were nine d (range, 8-17) and 16 d (range, 10-28), respectively. Acute GVHD of grade II-IV and chronic GVHD occurred in 51% and 27%, respectively. Overall survival rates at two yr for patients with SAA and hematological malignancies were 87% and 65%, respectively. The event-free survival at two yr for patients with hematological malignancies was 76%. We concluded that MMF-CSA appears equivalent to MTX-CSA for GVHD prophylaxis in patients receiving non-RIC G-BMT from HLA-identical siblings, with a tendency for more rapid neutrophil engraftment.