Allogeneic hematopoietic stem cell transplantation in infants is associated with significant morbidity and mortality.

BACKGROUND: Infants are subjected to hematopoietic stem cell transplantation (HSCT) due to malignant and non-malignant diseases. However, specific data concerning the outcome and transplantation-related complications in infants, as a separate age group, are limited. Our aim was to evaluate the impact of infancy on the outcome, toxicity, and complications after HSCT. METHODS: We retrospectively analyzed data of 55 infants that underwent HSCT in our unit from May 1997 until February 2020, emphasizing on the probability of overall survival (OS) and the cumulative incidence (CI) of transplantation-related mortality (TRM) and complications. RESULTS: We report a probability of OS of 61%, a CI of TRM at day 100 and 365 post transplantation of 22% and 30%, respectively, and additionally a CI of graft failure, acute graft-versus-host disease (GvHD), and infectious complications, 18%, 44%, and 39%, respectively. No statistically significant association was detected between the above mentioned parameters and diagnosis, the use of myeloablative or non-myeloablative/reduced toxicity conditioning regimens or the type of donor. CONCLUSIONS: We conclude that HSCT in infancy is associated with significant mortality and morbidity. This is possibly attributed to endogenous, age-related factors. More specifically, infants may be at a higher risk of toxicities due to the immaturity of developing vital organs and the deficiency of the newly adopted immune system that predisposes them to infectious complications. The development of GvHD further augments the danger of infections, in a potential vice-versa relationship. Moreover, there are few data on pharmacokinetics of chemotherapy agents, making safe and efficacious drug administration hard.

Is Carbapenem-resistant Klebsiella pneumoniae Infection in Pediatric Bone Marrow Transplantation Recipients Inevitably Fatal?

Carbapenem resistance, most notably in Klebsiella pneumonia (KPC), results in infections associated with significant morbidity and mortality. Here we report 2 cases of adolescent patients with KPC infection after high-risk bone marrow transplantation, who eventually succumbed from other causes and review the epidemiology and treatment options for KPC infections in this vulnerable population.

Successful long-term hematological and immunological reconstitution by autologous cord blood transplantation combined with post-transplant immunosuppression in two children with severe aplastic anemia.

aUCBT is a valuable curative option in pediatric patients with refractory idiopathic SAA and no available matched sibling or unrelated donors. Experience in the use of autologous cord blood units in patients with SAA is limited and private for-profit cord blood-banking programs are controversial. We report the successful treatment of two patients with SAA, aged 15 and 24 months, with autologous cord blood combined with immunosuppression. After conditioning with 200 mg/kg cyclophosphamide and ATG, 7.5 mg/kg, 32.2 × 107 /kg, and 3.8 × 107 /kg autologous cord blood nucleated cells were infused, respectively. One of our patients underwent transplantation after failure of IST. Both patients received post-transplant immunosuppression with cyclosporine for 12 months. They remain disease-free 6 years post-transplantation.

Acute gastrointestinal graft-versus-host disease in pediatric patients: serum albumin on day 5 from initiation of therapy correlates with nonrelapse mortality and overall survival.

The aim of the present study was to identify factors associated with the risk of development of gastrointestinal acute graft-versus-host disease (GI-aGVHD), as well as to evaluate the impact of various baseline parameters on response to treatment, nonrelapse mortality (NRM), and overall survival (OS) in pediatric patients with GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-SCT). We retrospectively analyzed 300 pediatric patients who underwent allo-SCT from HLA-matched related or volunteer unrelated donors in our institution. GI tract involvement was observed in 46 out of 133 patients with aGVHD grade II-IV. Severe aGVHD (grade III-IV) was more frequently observed among patients with GI-aGVHD in comparison with patients without GI involvement (P < .001). Treatment with steroids resulted in durable responses in 22/46 patients; 14 additional patients responded to salvage therapy, whereas 10 were refractory to all treatments administered. Using Cox regression analysis, we observed that serum albumin level ≥ 3 mg/dL on day 5 after the initiation of therapy with steroids was statistically significantly associated with decreased hazard of NRM and improved OS (P = .021 and P = .026, respectively). In our study, serum albumin level, early (+ day 5) after the onset of steroids in patients with GI-aGVHD, was a predictor of treatment outcome. Prospective randomized trials need to be performed to verify the predictive significance of serum albumin and the need for early intensification of immunosuppressive treatment.

Directed sibling donor cord blood banking for children with beta-thalassemia major in Greece: usage rate and outcome of transplantation for HLA-matched units.

Several cord blood banks store cord blood units from healthy siblings of patients, who are candidates for stem cell transplantation. We analyzed the quality characteristics of 50 cord blood units collected from families with beta-thalassemia major and the outcome of subsequent stem cell transplantations during a 15-year period. All cord blood units were found suitable for banking based on a minimum net volume of 40 ml. The mean volume of the units was 98.9 ml; the mean total nucleated cell count (NC) was 7.8 x 10(8) and the mean CD34+ cell count was 2.8 x 10(6). Eight out of twelve HLA matched collections were released for transplantation. All but one recipient belonged to Pesaro II-III risk classes. Three patients received a cord blood graft with >5 x 10(7) NC/kg . One of them with Pesaro class I disease engrafted, whereas the other two who failed to engraft, were re-transplanted with bone marrow from the same donor later. Cord blood grafts containing NCs <4 x 10(7)/kg combined with reduced volume bone marrow from the same donor were used in all 5 remaining cases and stable engraftment was achieved. All patients survived, 7/8 thalassemia-free. Cord blood banking from healthy siblings of children with beta-thalassemia major can result in a successful transplantation in cases in which there is HLA compatibility. However, in high-risk patients, the use of combined cord blood and bone marrow grafts seems necessary in order to ensure stable engraftment, especially when cord blood unit cell counts are low.

Successful hematopoietic stem cell transplantation in 2 children with X-linked chronic granulomatous disease from their unaffected HLA-identical siblings selected using preimplantation genetic diagnosis combined with HLA typing.

We report 2 children with X-linked chronic granulomatous disease (X-CGD) who underwent hematopoietic stem cell transplantation (HSCT) using grafts from their siblings selected before implantation to be both unaffected and HLA-matched donors. Preimplantation genetic diagnosis (PGD) along with HLA-typing were performed on preimplantation embryos by single-cell multiplex polymerase chain reaction using informative short tandem repeat markers in the HLA locus together with the gene region containing the mutations. Two singleton pregnancies resulted from the intrauterine transfer of selected embryos; these developed to term, producing 1 healthy female and 1 X-CGD carrier female, which are HLA-identical siblings to the 2 affected children. Combined grafts of umbilical cord blood (UCB) and bone marrow (BM) stem cells were administered to the recipients after myeloablative (MA) conditioning at the ages of 4.5 years and 4 years, respectively. Both patients are well, with complete donor hematopoietic and immunologic reconstitution, at 18 and 13 months posttransplantation, respectively. This report demonstrates that HSCT with HLA-matched sibling donors created by PGD/HLA typing of in vitro fertilized embryos is a realistic therapeutic option and should be presented as such to families with children who require a non-urgent HSCT but lack an HLA-genoidentical donor.

Successful HLA-identical hematopoietic stem cell transplantation in a patient with purine nucleoside phosphorylase deficiency.

PNP deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency, autoimmune hemolytic anemia, and by a complex of neurologic manifestations including ataxia, developmental delay, and spasticity. PNP protein catalyzes the phosphorolysis of deoxyinosine and deoxyguanosine. It is found in most tissues of the body but is expressed at the highest levels in lymphoid tissues. This tissue distribution explains why the lymphoid system is predominantly affected in PNP deficiency. We describe a five-yr-old boy with muscular hypertonia, impaired growth, autoimmune hemolytic anemia, and neutropenia who underwent HSCT from his HLA-identical sister. One yr post-HSCT, the boy developed normal immunological functions, and his neurological status improved.