Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cellreplete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/mL CD4 + and 1000/mL CD3 + cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure.
Hematopoietic stem cell transplantation (HSCT) is the standard treatment for patients with high-risk hematologic malignancies. Only approximately 25% of siblings are HLA-matched, and thus alternative donors-unrelated or haploidentical-are usually the only options available. This meta-analysis aimed to compare haploidentical HSCT with post-transplantation cyclophosphamide and unrelated donor (URD) HSCT. We searched the PubMed and Cochrane databases for pertinent studies indexed between 2008 and 2018. Twenty observational studies (with a total of 1783 haploidentical HSCT recipients and 6077 URD HSCT recipients) were included. Results for overall survival, graft-versus-host disease (GVHD), nonrelapse mortality (NRM), and relapse incidence were pooled. Measures of association used were hazard ratios and risk differences. The median age was 51 years for haploidentical transplant recipients and 52 years for URD transplant recipients. Peripheral blood stem cell (PBSC) grafts were more frequent in the URD transplant recipients (85%) than in the haploidentical transplant recipients (31%). Overall survival was not different between the 2 groups. NRM was lower for haploidentical transplantation. All forms of GVHD (acute grades II-IV and III-IV and moderate, severe, and extensive chronic) were lower with haploidentical donor HSCT. The risk of chronic GVHD was fairly proportional to the differential use of PBSC grafts across studies, however. All included studies were retrospective, representing the major limitation of this meta-analysis. In conclusion, haploidentical HSCT for hematologic malignancies achieved the same overall survival as URD HSCT, with a lower incidence of GVHD and NRM. The increased frequency of PBSC use in the unrelated donor group could partially explain the higher cGVHD rate. Haploidentical transplantation with post-transplantation cyclophosphamide should strongly be considered as the first option for adult patients with hematologic malignancies who do not have matched sibling donors in experienced centers. This systematic review has been registered at PROSPERO (65790).
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Introduction. COVID-19 pandemic has spread worldwide and reached HSCT centers in many countries. The first proven case of COVID-19 in Brazil was diagnosed in São Paulo by the end of February 2020. The Brazilian Society of Marrow Transplantation (SBTMO) promptly published local recommendations for the diagnosis and management of COVID-19 in HSCT centers. We describe the main clinical findings and outcomes of SARS CoV-2 infection and COVID-19 in 22 HSCT recipients from two Brazilian HSCT centers, followed up for at least 14 days. Methods. The detection of SARS CoV-2 infection was performed by RT-PCR in all transplant candidates before admission, and in all HSCT recipients with respiratory symptoms. Other respiratory viruses were also investigated by direct fluorescent assay (DFA) or RT-PCR. COVID-19 was managed according to the SBTMO recommendations. Results. From March to June 2020, SARS CoV-2 infection was detected in 5 asymptomatic patients (29.4%) and COVID-19 was diagnosed in 17 HSCT recipients with respiratory symptoms (7 AUTO, 6 MRD, 5 MUD and 4 HAPLO) at a median of 94 days after HSCT (range -6 to +1,850). The asymptomatic cases at diagnosis remained so during follow-up. Two asymptomatic patients were receiving the conditioning regimen when SARS CoV-2 was diagnosed. The median age at diagnosis was 39,2 (1-72) years. Five patients were children (1-12 years) and 17 were adults (19-72 years). Eleven patients (50%) had comorbidities, the most frequent being diabetes and hypertension. Fever, cough and diarrhea were the symptoms more frequently observed and occurred in 13 (76.4%), 7 (41.2%), and 5 (29.4%) of the 17 symptomatic patients, respectively. Symptoms such as anosmia and dysgeusia, which have been frequently associated with COVID-19 were not observed in this series. Eleven of the symptomatic patients (64.7%) showed altered CT or X-ray at diagnosis. Glass ground opacities were the images more frequently seen (63.6%). The median lymphocyte count was 619.5 (0-2,604) /mL. C-reactive protein and d-dimer ranged from 0.65 to 339 ng/mL and from 0.39 to 4,530 mg/L, respectively. Four (18%) HSCT recipients died (1 AUTO, 2 HAPLO, 1 MRD). COVID-19 was the cause of death in two of them. In the remaining two HAPLO HSCT recipients, KPC co-infection followed by septic shock had a major role in patients' death. Median age of patients who died was 39 (11-59) years, and two of them had comorbidities (hypertension and chronic lung disease). Conclusions. Symptoms of COVID-19 mimic other respiratory virus infections and specific diagnosis is mandatory. Interstitial pneumonia was frequent (around 65%). Clinical outcome of SARS Cov-2 infection or COVID-19 was moderate in the majority of the patients in the present series. However, the mortality rates observed in HSCT recipients (14.3% in AUTO; 20% in ALLO) were higher than in general population. Asymptomatic cases were seen in almost 30% of the patients, suggesting that frequent screening is necessary to control transmission in HSCT centers. Disclosures No relevant conflicts of interest to declare.
Cytomegalovirus (CMV) reactivation remains one of the main infectious complications following hematopoietic stem cell transplantation (HSCT). In this study, we explored the role of anti-CMV antibody titers in HSCT from alternative donors and to compare the risk of CMV reactivation between posttransplant cyclophosphamide-based haploidentical HSCT and antithymocyte globulin-based unrelated donor (URD) HSCT. We included 98 CMV-positive patients, 30 undergoing haploidentical HSCT and 68 undergoing URD HSCT. The majority of patients had a malignant disease (84%), received a myeloablative conditioning regimen (78%), and received a bone marrow graft (90%). The median pretransplantation anti-CMV IgG level was 109 U/mL. With median follow-up of 2.2 years, a total of 72 CMV reactivations occurred in 50 patients. There was no difference in CMV reactivation pattern between haploidentical HSCT recipients and URD HSCT recipients. In multivariable analysis until the first event, the incidence of CMV reactivation was higher in patients with anti-CMV IgG levels >100 U/mL (hazard ratio [HR], 2.38; P = .005) and in patients diagnosed with grade II-IV acute graft-versus-host disease (GVHD) (HR, 10.8; P = .003) after day +50 and lower in patients who received higher doses of CD34 cells (HR, .44; P = .006). In multivariable analysis for recurring events, the incidence of CMV reactivation was higher in patients receiving reducedintensity conditioning (HR, 1.69: P = .04) and in patients with acute GVHD (HR, 1.88; P = .02), and lower in those who received higher doses of CD34 cells (HR, .55; P = .01). In summary, we have shown that pretransplantation anti-CMV IgG titers are correlated with CMV reactivation risk. More studies are needed to assess how this information can be incorporated in HSCT. The use of high-dose cellular grafts, a modifiable risk factor, also protects against CMV reactivation.
The survival rates of children with high-risk acute myeloid leukemia (AML) treated with hematopoietic stem cell transplant (HSCT) range from 60% to 70% in high-income countries. The corresponding rate for Brazilian children with AML who undergo HSCT is unknown. We conducted a retrospective analysis of 114 children with AML who underwent HSCT between 2008 and 2012 at institutions participating in the Brazilian Pediatric Bone Marrow Transplant Working Group. At transplant, 38% of the children were in first complete remission (CR1), 37% were in CR2, and 25% were in CR3+ or had persistent disease. The donors included 49 matched-related, 59 matched-unrelated, and six haploidentical donors. The most frequent source of cells was bone marrow (69%), followed by the umbilical cord (19%) and peripheral blood (12%). The 4-year overall survival was 47% (95% confidence interval [CI] 30%–57%), and the 4-year progression-free survival was 40% (95% CI 30%–49%). Relapse occurred in 49 patients, at a median of 122 days after HSCT. There were 65 deaths: 40 related to AML, 19 to infection, and six to graft versus host disease. In conclusion, our study suggests that HSCT outcomes for children with AML in CR1 or CR2 are acceptable and that this should be considered in the overall treatment planning for children with AML in Brazil. Therapeutic standardization through the adoption of multicentric protocols and appropriate supportive care treatment will have a significant impact on the results of HSCT for AML in Brazil and possibly in other countries with limited resources.
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