The prevalence of apical periodontitis in patients prior to hematopoietic cell transplantation: a systematic review.

Objectives: This systematic review addressed the question: "What is the prevalence of apical periodontitis in patients prior to hematopoietic cell transplantation?" Materials and Methods: A systematic search was conducted in MEDLINE/PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Grey Literature Report. Eligibility criteria were based on the condition, content, and population strategy: the condition was the radiographic prevalence of apical periodontitis, the content comprised patients scheduled for hematopoietic stem cell transplantation, and the population consisted of adult and pediatric patients. The revised Risk of Bias in Nonrandomized Studies of Exposure tool was used to assess the quality of studies. The Grading Recommendations Assessments, Development, and Evaluation (GRADE) tool was used to assess the quality of evidence. Results: Eight studies were included in this review. The average number of patients with apical periodontitis was 15.65% (range, 2.1%-43.34%). One study was classified as having a very high risk of bias, 1 with a high risk of bias, and 6 with some concern for bias. GRADE analysis showed a very low certainty of evidence. Significant limitations concerning the absence of control over confounding variables were identified. Conclusions: With the caveat of the very low quality of evidence in the studies reviewed, there was a low to moderate prevalence of apical periodontitis in patients prior to undergoing hematopoietic cell transplantation.

Assessment of rehabilitation practices during hematopoietic stem cell transplantation in the United States: a survey.

Background: Rehabilitation therapy is important to treat physical and functional impairments that may occur in individuals receiving physically taxing, yet potentially curative hematopoietic stem cell transplants (HSCT). However, there is scarce data on how rehabilitation is delivered during HSCT in real-life setting. Our objective is to assess the rehabilitation practices for adult patients hospitalized for HSCT in the United States. Methods: A 48-question online survey with cancer centers with the top 10% HSCT volumes (per American registries). We obtained data on patient characteristics, rehabilitation therapy details (timing, indication, administering providers), physical function objective and subjective outcome measures, and therapy activity precautions. Results: Fourteen (out of 21) institutions were included. Rehabilitation therapy referrals occurred at admission for all patients at 35.7% of the centers for: functional decline (92.9%), fall risk (71.4%), and discharge planning (71.4%). Participating institutions had physical therapists (92.9%), occupational therapists (85.7%), speech language pathologists (64.3%) and therapy aides (35.7%) in their rehabilitation team. Approximately 71% of centers used objective functional measures including sit-to-stand tests (50.0%), balance measures (42.9%), and six-minute walk/gait speed (both 35.7%). Monitoring of blood counts to determine therapy modalities frequently occurred and therapies held for low platelet or hemoglobin values; but absolute neutrophil values were not a barrier to participate in resistance or aerobic therapies (42.9%). Discussion: Rehabilitation practices during HSCT varied among the largest volume cancer centers in the United States, but most centers provided skilled therapy, utilized objective, clinician and patient reported outcomes, and monitored blood counts for safety of therapy administration.

Colonization by Extended-Spectrum ß-Lactamase-Producing Enterobacterales and Bacteremia in Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Assessing the risk of multidrug-resistant colonization and infections is pivotal for optimizing empirical therapy in hematopoietic stem cell transplants (HSCTs). Limited data exist on extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) colonization in this population. This study aimed to assess whether ESBL-E colonization constitutes a risk factor for ESBL-E bloodstream infection (BSI) and to evaluate ESBL-E colonization in HSCT recipients. METHODS: A retrospective analysis of ESBL-E colonization and BSI in HSCT patients was conducted from August 2019 to June 2022. Weekly swabs were collected and cultured on chromogenic selective media, with PCR identifying the ß-lactamase genes. Pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) assessed the colonizing strains' similarities. RESULTS: Of 222 evaluated HSCT patients, 59.45% were colonized by ESBL-E, with 48.4% at admission. The predominant ß-lactamase genes were blaTEM (52%) and blaSHV (20%). PFGE analysis did not reveal predominant clusters in 26 E. coli and 15 K. pneumoniae strains. WGS identified ST16 and ST11 as the predominant sequence types among K. pneumoniae. Thirty-three patients developed thirty-five Enterobacterales-BSIs, with nine being third-generation cephalosporin-resistant. No association was found between ESBL-E colonization and ESBL-BSI (p = 0.087). CONCLUSIONS: Although the patients presented a high colonization rate of ESBL-E upon admission, no association between colonization and infection were found. Thus, it seems that ESBL screening is not a useful strategy to assess risk factors and guide therapy for ESBL-BSI in HSCT-patients.

Survival After Hematopoietic Stem Cell Transplantation in Severe Combined Immunodeficiency (SCID): A Worldwide Review of the Prognostic Variables.

This study aims to perform an extensive review of the literature that evaluates various factors that affect the survival rates of patients with severe combined immunodeficiency (SCID) after hematopoietic stem cell transplantation (HSCT) in developed and developing countries. An extensive search of the literature was made in four different databases (PubMed, Embase, Scopus, and Web of Science). The search was carried out in December 2022 and updated in July 2023, and the terms such as "hematopoietic stem cell transplantation," "bone marrow transplant," "mortality," "opportunistic infections," and "survival" associated with "severe combined immunodeficiency" were sought based on the MeSH terms. The language of the articles was "English," and only articles published from 2000 onwards were selected. Twenty-three articles fulfilled the inclusion criteria for review and data extraction. The data collected corroborates that early HSCT, but above all, HSCT in patients without active infections, is related to better overall survival. The universal implementation of newborn screening for SCID will be a fundamental pillar for enabling most transplants to be carried out in this "ideal scenario" at an early age and free from infection. HSCT with an HLA-identical sibling donor is also associated with better survival rates, but this is the least common scenario. For this reason, transplantation with matched unrelated donors (MUD) and mismatched related donors (mMRD/Haploidentical) appear as alternatives. The results obtained with MUD are improving and show survival rates similar to those of MSD, as well as they do not require manipulation of the graft with expensive technologies. However, they still have high rates of complications after HSCT. Transplants with mMRD/Haplo are performed just in a few large centers because of the high costs of the technology to perform CD3/CD19 depletion and TCRαß/CD19 depletion or CD34 + selection techniques in vitro. The new possibility of in vivo T cell depletion using post-transplant cyclophosphamide could also be a viable alternative for performing mMRD transplants in centers that do not have this technology, especially in developing countries.

Outcomes of upfront plerixafor use for mobilization in germ cell tumor patients.

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improved 5-year overall survival rates in relapsed/refractory germ cell tumors (GCTs) from 10% to 52%. Nearly 30% of GCT patients are deemed poor mobilizers after receiving several lines of prior therapy. There is limited data available regarding upfront plerixafor use in GCT patients. We predicted upfront plerixafor use would increase the amount of stem cells collected preventing subsequent mobilizations and improve time to curative therapy. A retrospective, single center, chart review of adult GCT patients who received plerixafor upfront for mobilization at a single center between January 1, 2013 and August 31, 2021 was performed. The primary objective was to evaluate the rate of successful peripheral blood CD34+ cell collections. Secondary objectives consisted of describing the impact of plerixafor use on mobilization and assessing auto-HSCT related outcomes. Sixteen patients received plerixafor upfront after an average of three prior lines of therapy (range: 2-5 lines). Successful collection (≥4 × 106 CD34+ cells/Kg collected within four days) was achieved in 15 (94%) patients in a median of one apheresis day (interquartile range: 1-2 days). All patients proceeded to an initial auto-HSCT and 12 patients (75%) completed both transplants as planned. Survival at 12 months was 50%. The significantly higher amount of CD34+ cells collected over less apheresis days demonstrated the clinical utility of upfront plerixafor and its potential to facilitate more efficient stem cell mobilization. There is a need for larger randomized studies with upfront plerixafor use in this unique patient population.

The Use of a High Flow PICC Catheter for Stem Cell and Lymphocyte Apheresis: The Initial Experience of a Pediatric Oncology Center in Brazil.

BACKGROUND: Autologous hematopoietic stem cell transplant (HSCT), characterized by high intensity chemotherapy followed by the infusion of HSC previously collected from the peripheral blood, is a procedure used in the treatment of several malignancies. In pediatrics, the apheresis procedure represents a challenge, due to the need for insertion of a rigid central venous catheter (CVC) in small children. The CVC is usually used for stem cell collection and then removed. Later, the patient will need a new device for cell infusion. AIM: We propose the use of one single catheter for both apheresis and infusion. METHODS: We present five children between 1 and 13 years of age who underwent apheresis using a high flow PICC catheter surgically inserted. RESULTS: All patients utilized a PICC line double lumen 5Fr (PowerPICC™ 5Fr DL BARD/USA) placed in the brachiocephalic vein tunneled on the chest, inserted under 24 h prior to apheresis to assure the devices were pervious. Three of the patients were diagnosed with solid tumor and one with acute lymphoblastic leukemia (ALL) awaiting Car-T Cell therapy. The four children who underwent autologous HSCT used the same catheter for cell infusion and remained with the catheter following discharge. The child who was submitted for Car-T Cell still awaits infusion and the catheter was removed. CONCLUSIONS: High flow PICC is a viable alternative for apheresis to maintain an adequate flow of 5 ml/s and can be used as a single catheter throughout the HSCT process, reducing the risks from anesthesia and the catheter insertion procedure. TYPE OF STUDY: Clinical Research.

Long-term remission of infantile Takayasu arteritis associated with germline CBL syndrome after allogeneic hematopoietic stem cell transplantation: A case report and literature review.

Takayasu arteritis (TA) is a large-vessel vasculitis that rarely presents in infancy. Casitas B-lineage lymphoma (CBL) syndrome is a rare genetic disorder due to heterozygous CBL gene germline pathogenic variants that is characterized by a predisposition to develop juvenile myelomonocytic leukemia (JMML). Vasculitis, including TA, has been reported in several patients. Herein, we describe a patient with CBL syndrome, JMML, and TA, developing long-term remission of this vasculitis after allogeneic hematopoietic stem cell transplant (HSCT), and perform a literature review of CBL syndrome with vasculitis or vasculopathy. We report a female patient with growth delay, developmental issues, and congenital heart disease who was admitted at 14 months of age with massive splenomegaly, lymphadenopathy, fever, and hypertension. Body imaging studies revealed arterial stenosis and wall inflammation of the aorta and multiple thoracic and abdominal branches. Whole exome sequencing revealed a pathogenic variant in CBL with loss of heterozygosity in blood cells, diagnosing CBL syndrome, complicated by JMML and TA. Allogeneic HSCT induced remission of JMML and TA, permitting discontinuation of immunosuppression after 12 months. Six years later, her TA is in complete remission off therapy. A literature review identified 18 additional cases of CBL syndrome with vasculitis or vasculopathy. The pathogenesis of vasculitis in CBL syndrome appears to involve dysregulated T cell function and possibly increased angiogenesis. This case advances the understanding of vascular involvement in CBL syndrome and of the genetic, immune, and vascular interplay in TA, offering insights for treating CBL syndrome and broader TA.

Neutrophil to lymphocyte ratio and systemic immune-inflammatory index as markers of response to autologous hematopoietic stem cell transplantation in persons with multiple sclerosis.

INTRODUCTION: Biomarkers that help to evaluate the immune system and could be useful in multiple sclerosis (MS) are the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). The objective of this work is to evaluate the significance of the SII index, PLR, and NLR before and after transplantation in individuals with MS who underwent autologous hematopoietic stem cell transplant (aHSCT) at a single institution. METHODS: Patients with MS who received an aHSCT between 2017 and 2022 were included in the study. NLR, PLR, and SII index were calculated prior to the transplant and 100 days after, and evaluation of the expanded disability status scale (EDSS) was done before the transplant and 12 months after. The cohort was divided into two groups: aHSCT responders (R) and nonresponders (NR). RESULTS: Fifty-eight individuals were examined: 37 patients in the responders group R group and 21 in NR group. There was no statistically significant difference in the SII, NLR, and PLR prior to the transplant, however at 100 days post-HSCT, NLR in the R group was 1.8 versus 3.1 in the NR group (p = 0.003), PLR was 194 versus 295, respectively (p = 0.024), meanwhile SII index was 489.5 versus 729.3 (p < 0.001). CONCLUSION: High NLR and SII index values after the aHSCT were associated with a worsening in the EDSS score. However, since this is the first ever study that compared NLR and SII index with the aHSCT response in persons with MS, further studies must be performed to corroborate this information.

Enterocytozoon bieneusi Infection after Hematopoietic Stem Cell Transplant in Child, Argentina.

We report a case of Enterocytozoon bieneusi infection in a pediatric hematopoietic stem cell transplant recipient in Argentina. Spores were visualized in feces using Calcofluor White and modified trichrome stainings. PCR and sequencing identified E. bieneusi genotype D in fecal samples and liver samples, confirming extraintestinal dissemination of the parasite.

Anti-Hla Donor-Specific Antibodies Are Associated to Infection and Not to the Engraftment Rate in Outpatient Haploidentical Hematopoietic Cell Transplantation.

Background: Recipients of a related haploidentical stem cell transplant (haplo-SCT) can have preformed antibodies to HLA donor's antigens. Objective: The aim of the study was to evaluate the engraftment rate and major clinical associations of anti-HLA donor-specific antibodies (DSA) at two mean fluorescence intensity (MFI) thresholds in recipients of an outpatient haplo-SCT. Methods: Seventy haplo-HCT recipients were analyzed. A virtual crossmatch was performed using the donor HLA typing and the recipient's anti-HLA DSA test results. Data for anti-HLA-A, -B, -C, and -DR were analyzed. Recipients with DSA ≥ 500 MFI were considered positive, and those with < 500 were considered negative; the same was adopted for MFI ≥ 1000. Results: Post-transplant infection was higher in recipients with DSA ≥ 500 MFI (84.6%, p = 0.041). First-year mortality was higher in DSA-positive patients ≥ 500 MFI, p = 0.004, and DSA ≥ 1000 MFI, p = 0.022, than in DSA-negative recipients. Graft failure in the first 100 days was not associated with DSA ≥ 500 or ≥ 1000 MFI. There was no difference in acute (a-GVHD) or chronic (c-GVHD) graft versus host disease between DSA-positive and negative patients. Conclusions: There was no association of anti-HLA DSA at MFI ≥ 500 and ≥ 1000 with graft failure, however, increased infection and 1st-year mortality were documented in related haplo-HCT at the MFI cutoffs studied.

The future of aplastic anemia treatment in Brazil: Lessons learned for global hematology.

Aplastic anemia (AA) is a rare serious hematologic disorder caused by hematopoietic stem cell failure in maintaining hematopoiesis. AA is virtually fatal if not treated, and diagnosis and therapy require extensive hematologic infrastructure. Academic medical centers in Brazil have continuously and significantly contributed to diagnostic tools and therapy development, from novel transplant strategies to drug combinations and implementation science in the national public health system. In the present review, we discuss how the collaborative effort among academic centers in hematology has contributed to improving health care for patients with aplastic anemia. We also discuss what needs are still unmet and how to overcome these challenges.

Treatment of graft versus host disease with photopheresis interferes in voriconazole therapeutic drug monitoring: A case study.

Extracorporeal photopheresis is an established procedure for refractory graft-versus-host disease, a major complication associated with notable morbidity and mortality in patients with allogeneic hematopoietic stem cell transplant. Despite being implemented over a decade ago, there is scant information about potential interactions or analytical interferences with concomitant drugs in this polymedicated population. Here we report the case of a pediatric patient diagnosed with cutaneous steroid-refractory acute graft-versus-host disease after unrelated allogeneic hematopoietic stem cell transplant that was treated with photopheresis. Analytical quantification of voriconazole by HPLC-PDA the day following photopheresis treatment did not permit therapeutic drug monitoring (TDM) due to the presence of interference at the voriconazole retention time. Following investigations, it was demonstrated that the interference is likely attributable to a psoralen-based compound. The interference was not present when samples were obtained prior to photopheresis, enabling TDM. This case underscores the relevance of communication among the members of the treating team to perform reliable TDM, especially in routine clinical practice of pediatric patients with complex diseases undergoing innovative treatments. This finding is relevant to voriconazole quantification by HPLC-PDA, frequently used in laboratories based in middle-income countries.

Anti-Hla Donor-Specific Antibodies Are Associated to Infection and Not to the Engraftment Rate in Outpatient Haploidentical Hematopoietic Cell Transplantation

ABSTRACT Background: Recipients of a related haploidentical stem cell transplant (haplo-SCT) can have preformed antibodies to HLA donor's antigens. Objective: The aim of the study was to evaluate the engraftment rate and major clinical associations of anti-HLA donor-specific antibodies (DSA) at two mean fluorescence intensity (MFI) thresholds in recipients of an outpatient haplo-SCT. Methods: Seventy haplo-HCT recipients were analyzed. A virtual crossmatch was performed using the donor HLA typing and the recipient's anti-HLA DSA test results. Data for anti-HLA-A, -B, -C, and -DR were analyzed. Recipients with DSA ≥ 500 MFI were considered positive, and those with < 500 were considered negative; the same was adopted for MFI ≥ 1000. Results: Post-transplant infection was higher in recipients with DSA ≥ 500 MFI (84.6%, p = 0.041). First-year mortality was higher in DSA-positive patients ≥ 500 MFI, p = 0.004, and DSA ≥ 1000 MFI, p = 0.022, than in DSA-negative recipients. Graft failure in the first 100 days was not associated with DSA ≥ 500 or ≥ 1000 MFI. There was no difference in acute (a-GVHD) or chronic (c-GVHD) graft versus host disease between DSA-positive and negative patients. Conclusions: There was no association of anti-HLA DSA at MFI ≥ 500 and ≥ 1000 with graft failure, however, increased infection and 1st-year mortality were documented in related haplo-HCT at the MFI cutoffs studied. (REV INVEST CLIN. 2023;75(5):249-58)

Total marrow irradiation in hematopoietic stem cell transplantation for hematologic malignancies.

Total body irradiation (TBI) has been an essential component of the conditioning regimen in hematopoietic cell transplantation for many years. However, higher doses of TBI reduce disease relapse at the expense of more significant toxicities. Therefore, total marrow irradiation and total marrow and lymphoid irradiation have been developed to deliver organ-sparing targeted radiotherapy. Data from different studies show that TMI and TMLI can be safely administered in escalating doses in association with different chemotherapy conditioning regimen protocols, in situations with unmet needs, such as multiple myeloma, high-risk hematologic malignancies, relapsed or refractory leukemias, and elderly or frail patients, with low rates of transplant-related mortality. We reviewed the literature on applying TMI and TMLI techniques in autologous and allogeneic hematopoietic stem cell transplantation in different clinical situations.

Unusual gingival actinomycosis post allogeneic hematopoietic stem-cell transplant: case report.

BACKGROUND: Allogeneic hematopoietic stem cell transplant (allo-HSCT) is used to treat several hematological diseases, but immunosuppression during allo-HSCT facilitates opportunistic microbial growth in tissues, such as actinomycosis. An effective diagnosis of opportunistic diseases is essential for correct management of the disease and preservation of the immunosuppressed patient's life. CASE DESCRIPTION: A 57-year-old female patient was diagnosed with extranodal nasal type NK/T cell lymphoma and underwent curative treatment with allo-HSCT. Twenty-one days after the last clinical follow-up, the patient presented a necrotizing lesion in the papilla region between the first and second molars of the second quadrant. Histopathological analysis showed the presence of a bacterial cluster consistent with Actinomyces infection, and a dense lymphoid infiltrate was also observed. Immunohistochemistry for CD20, CD3, and CD56 was performed to exclude the possibility of the recurrence of extranodal NK/T cell lymphoma. Oral microbiota profiling showed a huge increase in the abundance of Actinomyces bacteria in the subgingival region three weeks prior to appearance of the lesion. CONCLUSIONS: Opportunistic infections with an unusual clinical appearance are confounding factors in therapeutic decision-making. We present for the first time a case of actinomycosis in the gingival papilla region following allo-HSCT. We also highlight how microbiota profiling through next-generation sequencing could be used to anticipate bacterial infection diagnosis.

Application of mass cytometry to characterize hematopoietic stem cells in apheresis products of patients with hematological malignancies.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is a widely used therapy, but its success largely depends on the number and quality of stem cells collected. Current evidence shows the complexity of the hematopoietic system, which implies that, in the quality assurance of the apheresis product, the hematopoietic stem cells are adequately characterized and quantified, in which mass cytometry (MC) can provide its advantages in high-dimensional analysis. OBJECTIVE: This research aimed to characterize and enumerate CD45dim/CD34+ stem cells using the MC in apheresis product yields from patients with chronic lymphoid malignant diseases undergoing autologous transplantation at the Abu Dhabi Stem Cells Center. METHODS: An analytical and cross-sectional study was performed on 31 apheresis products from 15 patients diagnosed with multiple myeloma (n = 9) and non-Hodgkin lymphomas (n = 6) eligible for HSCT. The MC was employed using the MaxPar Kit for stem cell immunophenotyping. The analysis was performed manually in the Kaluza and unsupervised by machine learning in Cytobank Premium. RESULTS: An excellent agreement was found between mass and flow cytometry for the relative and absolute counts of CD45dim/CD34+ cells (Bland-Altman bias: -0.029 and -64, respectively), seven subpopulations were phenotyped and no lineage bias was detected for any of the methods used in the pool of collected cells. A CD34+/CD38+/CD138+ population was seen in the analyses performed on four patients with multiple myeloma. CONCLUSIONS: The MC helps to characterize subpopulations of stem cells in apheresis products. It also allows cell quantification by double platform. Unsupervised analysis allows results completion and validation of the manual strategy. The proposed methodology can be extended to apheresis products for purposes other than HSCT.

Herpesvirus Screening in Childhood Hematopoietic Transplant Reveals High Systemic Inflammation in Episodes of Multiple Viral Detection and an EBV Association with Elevated IL-1ß, IL-8 and Graft-Versus-Host Disease.

Infections remain a major cause of morbidity and mortality among hematopoietic stem cell transplant (HSCT) recipients. Unlike Epstein-Barr Virus (EBV) and Human Cytomegalovirus (HCMV), Human Herpesvirus (HHV) 6, HHV7 and HHV8 are not routinely monitored in many centers, especially in the pediatric population of low-medium income countries. We screened EBV, HCMV, HHV6, HHV7 and HHV8 in 412 leukocytes-plasma paired samples from 40 pediatric patients assisted in a tertiary hospital in Mexico. Thirty-two underwent allo-HSCT, whereas eight received auto-HSCT. Overall viral detection frequencies in allo- and auto-HSCT were: EBV = 43.7% and 30.0%, HCMV = 5.0% and 6.7%, HHV6 = 7.9% and 20.0% and HHV7 = 9.7% and 23.3%. HHV8 was not detected in any sample. Interestingly, HHV6 and HHV7 were more frequent in auto-HSCT, and HHV6 was observed in all episodes of multiple detection in auto-HSCT patients. We found EBV DNA in plasma samples, whereas HCMV, HHV6 and HHV7 DNA were predominantly observed in leukocytes, indicative of their expansion in cellular compartments. We also found that IL-1ß, IL-2, IL-6 and IL-8 were significantly increased in episodes in which multiple viruses were simultaneously detected, and samples positive for EBV DNA and graft-versus-host disease had a further increase of IL-1ß and IL-8. In conclusion, the EBV, HCMV, HHV6 and HHV7 burdens were frequently detected in allo- and auto-HSCT, and their presence associated with systemic inflammation.

Clinical outcome from hematopoietic cell transplant patients with bloodstream infection caused by carbapenem-resistant P. aeruginosa and the impact of antimicrobial combination in vitro.

Bloodstream infection (BSI) caused by carbapenem-resistant P. aeruginosa (CRPA) has high mortality in hematopoietic stem cell transplant (HSCT) recipients. We performed MIC, checkerboard, time-kill assay, PFGE, PCR, and whole genome sequence and described the clinical outcome through Epi Info comparing the antimicrobial combination in vitro. Mortality was higher in BSI caused by CRPA carrying the lasB virulence gene. The isolates were 97% resistant to meropenem displaying synergistic effect to 57% in combination with colistin. Seventy-three percent of the isolates harbored blaSPM-1 and Tn4371 and belonged to ST277. The synergistic effect in vitro with meropenem with colistin appeared to be a better therapeutic option.

First-line haploidentical stem cell transplantation in children and adolescents with severe aplastic anemia using mobilized peripheral blood as source of CD34+: Single-institutional experience in a transplant center from northeast Mexico.

INTRODUCTION: The only curative treatment for severe aplastic anemia in children is an allogeneic stem cell transplant; however, few patients have a matched related or unrelated donor. Haploidentical stem cell transplantation (haplo-SCT) using bone marrow (BM) and peripheral blood stem cells (PBSC) has been recently described as effective and safe. In this study, we retrospectively report the outcome of twelve pediatric patients who underwent haplo-SCT using only PBSC. METHODS: The conditioning regimen consisted on rabbit anti-thymocyte globulin (r-ATG) 2.5 mg/kg/d on days -7, -6,-5, and -4, and cyclophosphamide (Cy) 50 mg/kg/d on days -3 and -2. We used Cy 50 mg/kg/d on days +3 and +4, tacrolimus and mycophenolic acid as graft versus host disease (GVHD) prophylaxis. RESULTS: The median follow-up was 1,099 days (45-1258 days). The overall survival rate up-to-date is 83.3%. In 10 of the 12 patients, a sustained graft was achieved. None of the patients had acute or chronic GVHD. CONCLUSIONS: Haplo-SCT could be established as a first-line treatment when there is no matched related or unrelated donor. According to this short sample and previous reports, PBSC are a feasible option effectively used as the sole source of stem cells. Additionally, post-transplant cyclophosphamide remains a good strategy for GVHD prevention.

Hematopoietic stem cell transplantation in a patient with osteopetrosis and mutation in CLCN7: long-term follow-up / Trasplante de células progenitoras hematopoyéticas en un paciente con osteopetrosis y mutación en CLCN7: seguimiento a largo plazo

Abstract Background: Osteopetrosis is a rare hereditary bone dysplasia characterized by insufficient osteoclast activity that results in increased bone mineral density. Hematopoietic stem cell transplantation (HSCT) can reverse skeletal abnormalities and restore hematopoiesis. Case report: We present the case of a 3-year and 2-month-old male patient with the diagnosis of osteopetrosis. The patient underwent allogeneic HSCT (Allo-HSCT) using 100% compatible bone marrow from a related donor and received a myeloablative conditioning regimen and a CD34 cell dose (4.7 × 107/kg). In the early post-transplant, frequent complications such as pneumonitis, hypercalcemia, and hyperphosphatemia ocurred. With a suitable granulocytic graft and chimerism of 100%, it was considered a successful transplant. However, the patient showed a delayed platelet graft treated with a platelet-stimulating factor for 6 months. The patient is currently disease-free, outpatient follow-up, with no data on graft-versus-host disease, and no progressive neurological damage. Conclusions: Osteopetrosis is a childhood disease that requires clinical suspicion and early diagnosis. HSCT is necessary at an early age to prevent disease progression and sensorineural, hematological, and endocrinological functions damage that can lead to death.

Resumen Introducción: La osteopetrosis es una displasia ósea hereditaria poco común, caracterizada por una actividad osteoclástica deficiente que aumenta la densidad mineral ósea. Se considera que el trasplante de células progenitoras hematopoyéticas (TCPH) puede revertir las anormalidades esqueléticas y restaurar la hematopoyesis. Caso clínico: Se presenta el caso de un paciente de sexo masculino, de 3 años y 2 meses de edad, con diagnóstico tardío de osteopetrosis. Se realizó un TCPH alogénico de donador relacionado 100% compatible con médula ósea. Se utilizaron un régimen de acondicionamiento mieloablativo y una dosis celular de CD34 de 4.7 × 107/kg de peso. En el postrasplante temprano, el paciente desarrolló complicaciones como neumonitis, hipercalcemia e hiperfosfatemia. Con un injerto granulocítico adecuado y quimerismo del 100% se consideró un trasplante exitoso. Sin embargo, el paciente presentó retraso en el injerto plaquetario, por lo que se administró factor estimulante de plaquetas por 6 meses. Actualmente el paciente se encuentra libre de enfermedad, en seguimiento ambulatorio, sin datos de enfermedad del injerto contra el hospedero y con pruebas de neurodesarrollo sin deterioro neurológico progresivo. Conclusiones: La osteopetrosis es una enfermedad infantil que requiere una sospecha clínica y un diagnóstico temprano, ya que es necesario un TCPH a corta edad como tratamiento para evitar la progresión de la enfermedad y el deterioro de las funciones neurosensoriales, hematológicas y endocrinológicas que puede derivar en la defunción del paciente.