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Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered to be indicated for children and adolescents with high-risk or relapsed T-cell acute lymphoblastic leukemia (T-ALL); however, the outcomes are unsatisfactory. Killer cell immunoglobulin-like receptors (KIRs) are the main receptors on natural killer (NK) cells that play an important role in the graft-versus-leukemia effect after allo-HSCT. In allo-HSCT, when the recipient lacks a donor KIR-ligand (KIR-ligand mismatch in the graft-versus-host [GVH] direction), donor NK cells will be activated against recipient cells. KIR-ligand mismatch in the GVH direction improves outcomes after unrelated cord blood transplantation (UCBT) with acute myeloid leukemia, but the effect in T-ALL is unclear. We evaluated the impact of KIR-ligand mismatch in the GVH direction on the transplantation outcomes of children and adolescents with T-ALL who received UCBT. We conducted a retrospective study using a nationwide registry of the Japanese Society for Transplantation and Cellular Therapy. Patients diagnosed with T-ALL, aged 0 to 19 years, and who underwent first UCBT between 1999 and 2017 were included. A total of 91 patients were included in this study. In all, 23 (25.3%) percent of patients had KIR-ligand mismatch in the GVH direction. The 5-year leukemia-free survival (LFS) and overall survival (OS) rates after UCBT were 65.8% and 69.6%, respectively. In a multivariate analysis, KIR-ligand mismatch in the GVH direction was associated with a significant reduction in the relapse rate (hazard ratio [HR], 0.19; P = .002), resulting in better LFS (HR, 0.18; P =.010) and OS (HR, 0.26; P = .048) without increasing non-relapse mortality (NRM; HR, 1.90; P = .264). The cumulative incidence of GVH disease (GVHD) did not differ between patients with and without KIR-ligand mismatch (grade II-IV acute GVHD, 39.1% versus 36.8%, P = .648, grade III-IV acute GVHD, 13.0% versus 11.8%, P =.857, and chronic GVHD, 26.1% versus 22.9%, P =.736, respectively). Furthermore, acute and chronic GVHD were not associated with good patient outcomes. Notably, no relapse was observed in patients who received KIR-ligand mismatched UCBT in complete remission. KIR-ligand mismatch in the GVH direction improved LFS and decreased relapse rates without increasing NRM in children and adolescents with T-ALL who received UCBT, which was not mediated by GVHD., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Rationale: The gastrointestinal (GI) tract is a common target organ of graft-vs-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT) patients, and GI tract GVHD is often resistant to standard treatments such as corticosteroids. Moreover, longterm use of systemic corticosteroids sometimes induces adverse events such as infection. Beclomethasone dipropionate (BDP) is a potent, topically active corticosteroid, which is metabolized to an active derivative in the intestinal mucosa. Oral BDP therapy is reportedly effective against GI tract GVHD in adult HSCT patients, but its efficacy and safety in pediatric patients remain undefined. Here, we report three pediatric and young adult cases who were treated with oral BDP., Patient Concerns: Three (6-, 7-, and 18-year-old) patients developed stage 2 to 4 lower GI tract GVHD, which was resistant to standard immunosuppressive therapies., Diagnosis: Lower GI tract GVHD in these patients was histopathologically proven by endoscopic biopsy., Interventions: Oral administration of enteric-coated capsules of BDP (3-8 mg/day) was started for the treatment of lower GI tract GVHD., Outcomes: With the introduction of oral BDP therapy, their GI tract symptoms promptly resolved (abdominal pain, within 3-7 days; diarrhea, within 2-3 weeks). Subsequently, systemic immunosuppressive agents such as corticosteroids and mycophenolate mofetil were successfully tapered off. During oral BDP therapy, although cytomegalovirus antigenemia and Acinetobacter Iwoffii sepsis developed in 2 cases, both were curable with conventional treatments. In a young adult case, concomitant BK virus-associated hemorrhagic cystitis resolved after oral BDP was introduced and systemic immunosuppressive agents were reduced. Transient growth restriction was observed in a pediatric case who was treated with oral BDP for approximately 300days., Lessons: Our experiences suggest that oral BDP therapy is an effective approach for GI tract GVHD that is resistant to standard immunosuppressive therapies. Of clinical importance, our case suggests the possibility that oral BDP therapy may improve the immunosuppressive condition in GI tract GVHD patients by contributing to the reduction of systemic immunosuppressive medications as a result of prompt improvement of GI tract GVHD symptoms., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Reduced fertility is one clinical manifestation among other well known Fanconi anemia features. Most recipients of allogeneic hematopoietic stem cell transplantation suffer from secondary infertility owing to gonadal damage from myeloablative conditioning. In order to evaluate the rate of pregnancy in Fanconi anemia transplanted patients, we performed a retrospective analysis of female patients transplanted in 15 centers from 1976 to 2008. Among 578 transplanted Fanconi anemia patients, we identified 285 transplanted females of whom 101 patients were aged 16 years or over. Ten became pregnant (4 twice). Before hematopoietic stem cell transplantation all had confirmed Fanconi anemia diagnosis. Median age at transplantation was 12 years (range 5-17 years). Conditioning regimen consisted of cyclophosphamide with or without irradiation. During follow up, 5 of 10 patients presented signs of ovarian failure. Among those, 2 patients spontaneously recovered regular menses, and 3 received hormonal replacement therapy. Pregnancy occurred from four to 17 years after hematopoietic stem cell transplantation. Three patients had preterm deliveries, one patient had a hysterectomy for bleeding. All 14 newborns had normal growth and development without congenital diseases. In conclusion, recovery of normal ovarian function and a viable pregnancy is a realistic but relatively rare possibility even in Fanconi anemia patients following hematopoietic stem cell transplantation. Mechanisms of fertility recovery are discussed.

The effect and safety of combination prophylaxis for hepatic veno-occlusive disease (VOD) following stem cell transplantation (SCT) was retrospectively evaluated in a total of 53 children who survived until day 30. Prophylaxis was started on the day before conditioning, and heparin (10 unit/kg/hr) alone was used in 6 patients, PGE1 (5 ng/kg/min) plus heparin plus PTX (200 mg/day) in 17 patients, lipo-PGE1 (0.5 ng/kg/min) plus heparin plus PTX in 7 patients, and lipo-PGE1 plus heparin in 23 patients. Diagnosis of VOD was made based on McDonald's criteria in 5 cases (9.4%), but not on Jones' criteria. No statistically significant difference was observed in the incidence of VOD among each prophylaxis group. The degree of VOD was mild in all of 5 cases, and all recovered with continuation of the prophylactic procedure. Each prophylactic procedure was performed without any significant adverse effect except for seizure induced by lipo-PGE1 in one patient with Lennox syndrome. Since both the incidence and fatality rate of VOD in children undergoing SCT are approximately 20% according to most of the previous reports, the present study suggests the effectiveness of combination prophylaxis.

A 9-year-old girl with acute lymphoblastic leukemia in second remission underwent cord blood transplantation (CBT) from an HLA-mismatched (2 loci by serotype, 3 loci by genotype) unrelated donor. The infused nucleated cell count was 1.95 x 10(7)/kg. FK506 and mini-MTX were used to prevent graft-versus-host disease (GVHD), but grade II acute GVHD developed on the skin (stage III). The GVHD subsided after administration of corticosteroid, but marked hyperglycemia developed, which required transient insulin therapy for its control. Minimal residual disease (MRD) was assessed using a clone-specific probe for the JH region. MRD was positive before CBT, but became negative one month after CBT. Now, at 14 months after CBT, the patient is in a disease-free state without detectable MRD. These observations suggest that CBT with two mismatched HLA loci can be performed safely, and that sequential analysis of MRD is useful for evaluation of the disease status after CBT.

We report a 1-year-old boy with infantile lymphoblastic leukemia in first complete remission who received a cord blood stem cell transplantation (CBSCT) from an HLA identical sibling. We collected 120 ml of cord blood when his brother was born, which contained 4.2 x 10(8) mononuclear cells (4.2 x 10(7)/kg) and 3.1 x 10(5) CFU-GM (3.1 x 10(4)/kg). One month prior to transplantation, he showed persistent fever and liver dysfunction, and was finally diagnosed as having primary cytomegalovirus (CMV) infection which was demonstrated by elevation of serum anti-CMV-IgM. The administration of ganciclovir dramatically improved the clinical symptoms and abnormal laboratory findings, and was continued up to 1 month after transplantation to suppress the CMV reactivation. The preconditioning regimen consisted of busulfan (16 mg/kg/4 days) and cyclophosphamide (120 mg/kg/2 days), and cyclosporin A (CyA) alone was used for graft-versus-host disease (GVHD) prophylaxis. Fever suspicious of grade I GVHD developed on day 19, but subsided by increasing the dose of CyA. The WBC and platelet counts reached greater than 1,000/microliter and 50 x 10(3)/microliter on days 12 and 42, respectively. It is now at 13 months since transplantation, and he remains in a disease free state.

Although autologous tandem hematopoietic SCT has improved the prognosis of patients with advanced high-risk neuroblastoma, the results remain unsatisfactory. In an attempt to induce the graft-versus-tumor effect, we performed autologous PBSCT followed by allogeneic cord blood transplantation in three consecutive advanced neuroblastoma cases with marked BM infiltration and high MYCN amplification. Severe acute complications did not occur in any patient and they have maintained disease-free survival for 37-60 months. This strategy appears to be feasible and effective for the treatment of extremely high-risk neuroblastoma cases. [ABSTRACT FROM AUTHOR]

The Fcγ receptor IIIb (FcγRIIIb), a receptor for the Fcγ region of IgG, is specifically expressed on neutrophils. It has two allelic polymorphisms, NA1 and NA2, which are highly immunogenic and act as targets in alloimmune or autoimmune neutropenia. Thus, neutrophil antigens (NA) compatibility of donor/recipient pairs might be expected to affect the engraftment of neutrophils after allogeneic SCT (allo-SCT). Here, the impact of NA compatibility of 17 patients and their donors undergoing allo-SCT with a myeloablative regimen was determined. Leukocyte depletion filters were used for all transfusions before and post-SCT; most patients received G-CSF after transplant. Major mismatches for NA1 and NA2 were present in 1 and 7 patient/donor pairs, respectively. These eight patients receiving NA major-mismatched allo-SCT were compared with nine patients who received NA compatible allo-SCT. Engraftment of neutrophils and the incidence of post-engraftment neutropenia were found to be identical in the two groups. Despite the limitations in statistical power because of the small number of patients analyzed, these observations suggest that the major mismatching for NA2 antigen has little impact on the engraftment of neutrophils after myeloablative allo-SCT, at least in patients transfused using leukocyte depletion filters and receiving G-CSF after transplantation.Bone Marrow Transplantation (2009) 43, 229–235; doi:10.1038/bmt.2008.311; published online 22 September 2008 [ABSTRACT FROM AUTHOR]