A Japanese retrospective study of non-tuberculous mycobacterial infection in children, adolescents, and young adult patients with hematologic-oncologic diseases.

Non-tuberculous mycobacterial infection (NTM) is rare in healthy children, with lymphadenitis being the most common presentation. Immunocompromised populations are known to be at high risk, but the clinical picture of NTM infection in pediatric hematology/oncology patients is unclear. In this nationwide retrospective analysis of patients under the age of 40 treated in Japanese pediatric hematology/oncology departments who developed NTM infection between January 2010 and December 2020, 36 patients (21 patients with hematopoietic stem cell transplantation (HSCT) and 15 nontransplant patients) were identified. Post-transplant patients were infected with NTM at 24 sites, including the lungs (n = 12), skin and soft tissues (n = 6), bloodstream (n = 4), and others (n = 2). Nine of twelve patients with pulmonary NTM infection had a history of pulmonary graft-versus-host disease (GVHD), and rapid-growing mycobacteria (RGM) were isolated from five of them. In nontransplant patients, the primary diseases were acute lymphoblastic leukemia (ALL; n = 5), inborn errors of immunity (IEI; n = 6), and others (n = 4). All cases of ALL had bloodstream infections with RGM, whereas all cases of IEI were infected with slow-growing mycobacteria (SGM). In summary, three typical clinical scenarios for pediatric hematology/oncology patients have been established: RGM-induced pulmonary disease in patients with pulmonary GVHD, RGM bloodstream infection in patients with ALL, and SGM infection in patients with IEI. Our findings suggest that NTM must be regarded as a pathogen for infections in these high-risk patients, especially those with pulmonary GVHD, who may require active screening for NTM.

Vedolizumab for children with intestinal graft-versus-host disease: a case report and literature review.

Acute graft-versus-host disease (aGVHD) is a challenging complication of allogeneic hematopoietic stem cell transplantation, and alternative therapies for patients showing inadequate response to steroids are limited. Vedolizumab, an anti-α4ß7 integrin antibody widely used for treating inflammatory bowel diseases, has recently been studied in adult patients with steroid-refractory intestinal aGVHD. However, few studies have examined its safety and effectiveness in pediatric patients with intestinal aGVHD. We report the case of a male patient with intestinal late-onset aGVHD treated with vedolizumab. He underwent allogeneic cord blood transplantation for warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and developed intestinal late-onset aGVHD 31 months after transplantation. The patient was refractory to steroids; however, vedolizumab was initiated 43 months after transplantation (at the age of 7 years) and the symptoms of intestinal aGVHD were alleviated. Additionally, favorable endoscopic findings were observed, such as reduction of erosion and regenerative epithelial growth. We also evaluated the efficacy of vedolizumab in 10 patients with intestinal aGVHD (9 from the literature review and the present case). Six patients (60%) showed an objective response to vedolizumab. No serious adverse events were observed in any patients. Vedolizumab is a potential treatment option for steroid-refractory intestinal aGVHD in pediatric patients.

Clinical Impact of Melphalan Pharmacokinetics on Transplantation Outcomes in Children Undergoing Hematopoietic Stem Cell Transplantation.

Melphalan is widely used for hematopoietic stem cell transplantation (HSCT) conditioning. However, the relationship between its pharmacokinetic (PK) and transplantation outcomes in children has not been thoroughly investigated. We prospectively analyzed the relationship between melphalan area under the curve (AUC) and transplantation outcome and examined the development of a predictive model for melphalan clearance in children. This study included 43 children aged 0 to 19 years who underwent HSCT following a melphalan-based conditioning regimen from 2017 to 2021. In univariable analysis, high-melphalan AUC resulted in a significantly lower cumulative incidence of acute graft-versus-host disease and a higher cumulative incidence of thrombotic microangiopathy, although no significant difference was observed in survival. Regression analysis of a randomly selected derivation cohort (n = 21) revealed the following covariate PK model: predicted melphalan clearance (mL/min) = 6.47 × 24-h urinary creatinine excretion rate (CER, g/day) × 24-h creatinine clearance rate (CCR, mL/min) + 92.8. In the validation cohort (n = 22), the measured melphalan clearance values were significantly correlated with those calculated based on the prediction equation (R2 = 0.663). These results indicate that melphalan exposure may be optimized by adjusting the melphalan dose according to CER and CCR.

Acute pancreatitis following allogeneic hematopoietic stem cell transplantation in children.

Acute pancreatitis (AP) is a potential complication of hematopoietic stem cell transplantation (HSCT), but its incidence and risk factors remain unclear. Thus, we reviewed the cases of 259 consecutive children who received allogeneic HSCT at our institution between January 2000 and December 2017 to determine the incidence and risk factors of AP. Thirteen patients developed AP during a median follow-up period of 4.4 years. The median time from HSCT to AP onset was 80 days (range 29-2426 days), and cumulative incidence (CI) at 4 years was 5.0% [95% confidence interval (95% CI) 2.7-8.3%]. The CI of AP was significantly higher in patients who received bone marrow or peripheral blood stem cells than in those who received cord blood (7.2% versus 0.0% at 4 years, P = 0.02) and was higher in patients who developed grade II-IV acute graft-versus-host disease (GVHD) than in those who did not (31.4% versus 1.4% at 4 years, P < 0.001). Multivariate analysis showed that grade II-IV acute GVHD was an independent risk factor for AP [hazard ratio 15.2 (95% CI 4.1-55.8), P < 0.001] and was strongly associated with post-HSCT AP in children.

[Disseminated Aspergillus siamensis infection following haploidentical bone marrow transplantation for chronic granulomatous disease].

An 18-year-old male patient who had been diagnosed with chronic granulomatous disease at 2 years old and suffering from repeated severe infections underwent human leukocyte antigen haploidentical bone marrow transplantation from his mother using reduced intensity conditioning. After engraftment, donor lymphocyte infusion was initiated to decrease donor chimerism on day 96. On day 120, acute graft-versus-host disease occurred; hence, steroid administration was initiated. On day 173, a generalized convulsion occurred; multiple abscesses were observed in the brain, lung, kidney, and prostate. Aspergillus siamensis of unknown pathogenic status was cultured in the abscess fluid from the brain, prostate, and kidney; accordingly, he was diagnosed with disseminated aspergillosis involving the brain, prostate, lungs, and kidney. Despite using a combination of various antifungal drugs, he died of multiple organ failure on day 239. Disseminated aspergillosis following the hematopoietic stem cell transplantation is a fatal complication. If infection symptoms are observed, the presence of any fungal antigens should be examined. Appropriate samples should be promptly collected, and adequate antifungal drugs should be administered based on the fungal species and drug sensitivity results.

Allogeneic stem cell transplantation with reduced intensity conditioning for patients with adrenoleukodystrophy.

OBJECTIVE: The prognosis of adrenoleukodystrophy (ALD)with neurological involvement is generally dismal; however, allogeneic stem cell transplantation (SCT) is recognized as effective to stabilize or improve the clinical symptoms of ALD. Herein, we report the clinical outcomes of patients with ALD who consecutively underwent allogeneic stem cell transplantation with reduced intensity conditioning at our institution. PATIENTS: Sixteen patients with ALD, who were symptomatic (n = 14) or presymptomatic (n = 2), received SCT from 2010 to 2016. The stem cell source was cord blood (n = 14), or bone marrow from a human leukocyte antigen identical sibling (n = 2). The conditioning regimen prior to transplantation was reduced intensity and consisted of fludarabine (125 mg/m2), melphalan (140 mg/m2) and low dose total body irradiation (TBI) of 4Gy (n = 15) or 3Gy (n = 1). RESULTS: Primary engraftment was obtained in 11 patients, and 4 of the 5 patients who lost the primary graft received a second cord blood transplantation and were engrafted. Five years overall and event-free survival were 90.9% and 61.1% respectively, with a median of 45 months (range 16-91). Loes score stabilized or improved by 18 months after transplantation except for patients with internal capsule involvement. CONCLUSION: Allogeneic SCT with reduced intensity conditioning for patients with ALD was safely performed without major transplant-related complications even in symptomatic patients and neurological symptoms were stabilized after SCT in patients without internal capsule involvement.

Heart Failure Caused by Atrial Fibrillation in a Patient with Isolated Adrenocorticotropic Hormone Deficiency and Hashimoto's Thyroiditis.

We report the case of a 75-year-old female patient with a history of Hashimoto's thyroiditis who presented with congestive heart failure caused by atrial fibrillation associated with isolated adrenocorticotropic hormone (ACTH) deficiency. This is the first case of the combination of these complex conditions. Clinical conditions in a patient with isolated ACTH deficiency and Hashimoto's thyroiditis can be variable. Thus, it is sometimes difficult to establish a diagnosis. The mechanism underlying heart failure may be complex in some cases. Various conditions can affect patients simultaneously. Therefore, making a proper diagnosis is necessary to improve the patient's prognosis.