High rates of ovarian function preservation after hematopoietic cell transplantation with melphalan-based reduced intensity conditioning for pediatric acute leukemia: an analysis from the Japan Association of Childhood Leukemia Study (JACLS).

Women are at high risk of hypergonadotropic hypogonadism after hematopoietic cell transplantation (HCT). Hypogonadism is universal after irradiation or busulfan. We hypothesized that reduced intensity conditioning (RIC) might protect ovarian function after HCT. We retrospectively reviewed data from patients with acute leukemia treated according to the Japan Association of Childhood Leukemia Study and nationwide multicenter study protocol. We selected 11 female patients with acute leukemia who received first HCT with RIC, had survived for three or more years after HCT, and were aged ≥ 12 years at the last follow-up visit. Median age at diagnosis, HCT, and last visit were 8, 10, and 17 years. Six patients received HLA-matched bone marrow (BM), two HLA-mismatched BM, and three cord blood. Melphalan was used as conditioning regimen in all patients. At the last visit, six of seven post-pubertal patients at transplantation recovered menstruation, and four of four patients who underwent transplantation at the pre-pubertal began menstruation. Height z scores showed no significant reduction between pre-transplant and post-transplant. No patients received growth hormone treatment. Only one recipient displayed subclinical hypothyroidism. Melphalan-based RIC may be an encouraging option for patients with acute leukemia to avoid ovarian and endocrine dysfunction after HCT.

Longitudinal observation of serum anti-Müllerian hormone in three girls after cancer treatment.

Gonadal dysfunction and infertility are major endocrinological late effects among childhood cancer survivors. Chemotherapy and radiation have gonadotoxic effects and diminish the ovarian reserve. The serum concentration of anti-Müllerian hormone (AMH) is a useful marker of ovarian reserve in survivors. We conducted a longitudinal study to investigate the variations of AMH in evaluating the acute and chronic effects of cancer therapy on the ovary. Three young female patients with different hematological diseases were registered, and their medical records were reviewed. Patient 1 with myelodysplastic syndrome received reduced-intensity hematopoietic stem cell transplantation (HSCT) at 10 yr of age. Breast development and menarche occurred spontaneously after HSCT; however, AMH level became undetectable and gonadotropin did not increase. Patient 2 with acute lymphoblastic leukemia had been receiving chemotherapy since 11 yr of age. AMH level became undetectable but increased after chemotherapy and was associated with regular menstruation. Patient 3 with acute myeloid leukemia received chemotherapy at 13 yr of age and myeloablative HSCT at 14 yr of age. AMH level became undetectable after HSCT, and the patient developed amenorrhea. These different patterns in the recovery phase demonstrated that the AMH level immediately after the end of cancer therapy is inappropriate for the evaluation of the ovarian reserve.

Primary renal neuroblastoma with metastasis and matrix metalloproteinase-14 expression.

We herein report the rare case of a 4-year-5-month-old boy who presented with primary renal neuroblastoma. The patient developed repeated lung and liver metastatic recurrences, but, following a combination of chemotherapy, radiation therapy and aggressive surgical resection, the patient is now in remission. To investigate the pathogenesis of lung metastasis, immunohistochemistry was performed for matrix metalloproteinase-9 and -14 (MMP-9 and MMP-14), molecular markers of invasion, metastasis and angiogenesis in neuroblastoma. In the present case, MMP-9 expression was not observed, but MMP-14 expression was detected in the primary lesion and was more highly expressed in the metastatic lesion compared with the primary one. Given the MMP-14 staining in other cases, expression of MMP-14 may be associated with the aggressiveness of the tumor. This suggests that selected clones with high MMP-14 expression in the primary tumor might metastasize and form MMP-14-rich lesions.

Mycobacterium avium complex-associated peritonitis with CAPD after unrelated bone marrow transplantation.

Peritonitis remains an important complication of peritoneal dialysis and is mostly caused by aerobic enteric bacteria. Non-tuberculous mycobacteria (NTM)-associated peritonitis is an unusual but serious infection, requiring special culture techniques to avoid delay in diagnosis. We report the case of an 11-year-old girl with aplastic anemia on ambulatory peritoneal dialysis who had Mycobacterium avium complex-associated peritonitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case emphasizes that we should be constantly cautious about NTM infection in allo-HSCT recipients, especially when standard cultures are negative and the infection is refractory to empirical antibiotic therapy.

Low serum concentrations of anti-Müllerian hormone are common in 53 female childhood cancer survivors.

BACKGROUND/AIMS: Gonadal dysfunction is one of the major endocrinological late effects among childhood cancer survivors (CCSs). Periodic screening evaluation of gonadotropins and sex steroids has been recommended, although it remains difficult to predict gonadal function and reproductive capacity in childhood. We evaluated the effects of cancer treatments on the ovarian function of Japanese female CCSs by measuring serum levels of anti-Müllerian hormone (AMH) and gonadotropin. METHODS: This was a retrospective, cross-sectional study at a single hospital. RESULTS: Among 53 female CCSs, 28 (53%) had a decreased AMH level, while only 16 (30%) had an increased follicle-stimulating hormone (FSH) level. AMH was low in all patients with high FSH, while FSH was not elevated in 43% of patients with a low AMH level. AMH was low in 8 of 9 patients with no breast development, 11 of 14 patients with no spontaneous menstruation, and 3 of 22 patients with regular menstrual cycles. CONCLUSION: Measurement of AMH concentration is useful as a marker of ovarian reserve in female CCSs for detecting primary gonadal deficiency, particularly among patients without increased gonadotropin levels.

Hematopoietic stem cell transplantation with reduced intensity conditioning from a family haploidentical donor in an infant with familial hemophagocytic lymphohistocytosis.

Allogeneic hematopoietic stem cell transplantation is the only curative method for patients with familial hemophagocytic lymphohistiocytosis (FHL). We present a case of a 3-month-old girl with Munc13-4 mutation (FHL3), who underwent bone marrow transplantation (BMT) from her human leukocyte antigen-haploidentical mother following reduced intensity conditioning (RIC) with fludarabine, melphalan, and busulfan. Engraftment after BMT was generally uneventful, with only mild acute graft versus host disease. Munc13-4 protein was restored following BMT, and she is well and free of disease 14 months after BMT. These results suggest that BMT with RIC from a family haploidentical donor may sufficiently restore immune regulation in infants, while lessening treatment-related mortality and long-term sequelae.

Anthracyclines for acute lymphoblastic leukemia in a child with congenital long QT syndrome.

Anthracyclines are key drugs for the treatment of children with acute lymphoblastic leukemia (ALL). However, anthracyclines are known to induce QT prolongation, and life-threatening complications, such as torsades de pointe may also occur. To date, there have been no reports on the use of anthracyclines in patients with congenital long QT syndrome (LQTS). We report a child with ALL complicated by congenital LQTS who was treated with anthracyclines. The administration of anthracyclines caused QT-interval prolongation, but this was uneventful with the concomitant administration of magnesium sulfate.

Successful treatment by double filtrate plasmapheresis in a pregnant woman with the rare P blood group and a history of multiple early miscarriages.

Individuals of P type, a rare blood group, have anti-PP(1)P(k) antibody in their serum, which causes spontaneous abortion in the early stages. We report a patient of p type suffering from multiple spontaneous abortions. We also review previously reported cases from published work. A 36-year-old woman (gravida 2, para 0) was referred to our hospital because of habitual abortion. At the third pregnancy, we started double filtration plasmapheresis (DFPP) from 7 weeks 3 days to remove the antibody. We attained rapid decline in the titer and normal fetal growth. Gradual tapering of the DFPP frequency caused neither a rebound of the titer nor growth retardation. During the course, she experienced only one episode of catheter infection as an adverse effect. At 37 weeks 3 days, after 57 DFPP repetitions, a 2496 g girl was delivered by cesarean section. The infant suffered neither from anemia nor from severe jaundice. A review of previous reports indicates that the titer of the pathogenic antibody should be kept as low as possible from the early gestational stage in P-incompatible habitual abortion cases, otherwise the case typically comes to an unfavorable outcome. Plasma exchanges with fresh plasma potentially induce contamination by either known or unknown pathogens. Such risks are reduced using DFPP because the volume of albumin solution that replaces fresh plasma is less than that by plasma exchange. The present case, along with previous reports, shows that DFPP is an effective therapy for treating P-incompatible pregnancy.