Tomoko Waragai

T‐cell‐replete haploidentical stem cell transplantation is highly efficacious for relapsed and refractory childhood acute leukaemia

Despite improvements in first‐line therapies, the outcomes of relapsed or refractory childhood acute leukaemia that has not achieved complete remission after relapse, has relapsed after stem cell transplantation (SCT), has primary induction failure and has relapsed with a very unfavourable cytogenetic risk profile, are dismal.

Relapse of minimal change nephrotic syndrome after intravitreal bevacizumab.

Reported herein is a case of relapse of nephrotic syndrome (NS) after intravitreal injection of bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), in a 16‐year‐old girl. She had a diagnosis of steroid‐dependent NS and had been treated with prednisolone, and remained in remission. The patient had had visus brevior 10 years previously, and was diagnosed with severe myopic choroidal neovascularization (mCNV). Intravitreal bevacizumab was given for mCNV. At 9 days after intravitreal injection of bevacizumab, proteinuria was positive. The patient had relapse of NS caused by bevacizumab, and steroid pulse therapy was then given and the proteinuria resolved. It is necessary to take particular care to prevent NS relapses in patients with mCNV treated with intravitreal bevacizumab.

Loss of mismatched HLA in myeloid/NK cell precursor acute leukemia relapse after T cell-replete haploidentical hematopoietic stem cell transplantation.

Myeloid/natural killer cell precursor acute leukemia (MNKL) is an aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (SCT). We report a patient with MNKL who had a donor lymphocyte infusion (DLI) for relapse after T cell‐replete human leukocyte antigen (HLA)‐haploidentical SCT, but relapsed again 20 months later with loss of mismatched HLA. This case suggests that a strong graft‐versus‐leukemia effect of haploidentical SCT can be expected in MNKL patients. In the haploidentical setting, DLI should be considered for patients with relapsed leukemia whose leukemic cells have not lost HLA cell surface expression. Pediatr Blood Cancer 2014; 61:1880–1882.

Comprehensive technical and patient-care optimization in the management of pediatric apheresis for peripheral blood stem cell harvesting

BACKGROUND Pediatric apheresis for peripheral blood stem cell transplantation should be carried out with due concern for low corporeal blood volume and vulnerability to hypocalcemia-related complications, hypovolemic shock, and hypervolemic cardiac overload. STUDY DESIGN AND METHODS We retrospectively investigated a total of 267 apheresis procedures from 1990 to 2013 on 93 children between 0 and 10 years old, including 89 patients and 4 healthy donors, with body weights of 6.3 to 44.0 kg. RESULTS The median CD34+ cell yield per apheresis procedure was 2.3 × 106 CD34+ cells/kg (0.2-77.9 × 106 CD34+ cells/kg). Adverse events occurred in 11.6% of procedures (n = 31), including mild perivascular pain (n = 12), emesis (n = 9), hypotension (n = 3), urticaria (n = 2), numbness (n = 2), chest pain (n = 1), facial flush (n = 1), and abdominal pain (n = 1). Among hypotensive events, shock in a 9.6 kg one-year-old boy required emergency treatment in 1996. Thereafter, we adopted continuous injection of calcium gluconate, ionized calcium monitoring, central venous catheter access and circuit priming with albumin in addition to concentrated red cells. Since then we have had fewer complications: 16.4% per apheresis during 1990-1997 versus 5.8% during 1998-2013. No healthy pediatric donors suffered from any late-onset complications related to apheresis or G-CSF administration. CONCLUSION By employing appropriate measures, peripheral blood stem cell apheresis for small children can have an improved safety profile, even for children weighing <10 kg.

Clinical analysis of combination therapy for febrile neutropenic patients in childhood cancer

The objective of this study was to evaluate the efficacy and safety of our combination therapy in febrile neutropenic children with cancer.

Malignant peritoneal mesothelioma in a child: chemotherapy with gemcitabine and platinum was effective for the disease unresponsive to other treatments

Malignant peritoneal mesothelioma in children is a very rare disease and has a poor prognosis. Unlike malignant mesothelioma in adults, there is no clear causal association between this very rare malignancy in children and asbestos exposure. We report a case of peritoneal mesothelioma in an 11-year-old boy who presented with ascites. He was diagnosed with malignant mesothelioma on the basis of histopathological findings. His disease showed resistance to pemetrexed, but was treated successfully with platinum-based therapy with gemcitabine. He has achieved long-term survival in partial remission with stable disease.

Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1

Background: Activated phosphatidylinositol‐3‐OH kinase &dgr; syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory tract infections, lymphoid hyperplasia, and Herpesviridae infections caused by germline gain‐of‐function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) can be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, methods, and outcomes of HSCT for APDS1 remain undefined. Objective: Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. Methods: We reviewed retrospectively the medical records of cohorts undergoing HSCT at collaborating facilities. Results: Thirty‐year overall survival was 86.1%, but event‐free survival was 39.6%. Life‐threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence and were common indications for HSCT. Nine patients underwent HSCT with fludarabine‐based reduced‐intensity conditioning. Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. Conclusion: Patients with APDS1 showed variable clinical manifestations. Life‐threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine‐based reduced‐intensity conditioning–HSCT ameliorated clinical symptoms, but transplantation‐related complications were frequent, including graft failure. GRAPHICAL ABSTRACT Figure. No caption available.

T cell replete–haploidentical second hematopoietic stem cell transplantation for primary graft failure in pediatric patients with hematologic malignancies

GF is one of the fatal complications of allogeneic HSCT. To rescue patients with primary GF, a second HSCT should be conducted as soon as possible, but the optimal donor source and technique have yet to be established. In this study, we retrospectively analyzed six children with hematologic malignancies who received TCR‐haploidentical second HSCT for primary GF. The median interval between the prior HSCT and the second HSCT was 37.5 days. All patients received fludarabine and ATG containing reduced‐intensity re‐conditioning before the second HSCT. All patients, except one who died early, achieved both neutrophil and Plt engraftment at a median time of 15 and 33 days, respectively. Chimerism analysis showed that all engrafted patients achieved complete donor chimerism within 3 weeks. Four patients developed acute GVHD, and three patients developed chronic GVHD. TRM occurred in two patients. Median follow‐up of the four survivors was 6.8 years, and all remained in sustained remission until the last follow‐up. These results suggested that a TCR‐haploidentical second HSCT for pediatric patients is feasible, and this approach may provide a potent option for children with primary GF.

Successful therapy with tonsillectomy plus pulse therapy for the relapse of pediatric IgA nephropathy treated with multi-drugs combination therapy

Immunoglobulin A nephropathy (IgAN) is the most common form of chronic glomerulonephritis worldwide.　In Japan, the treatment for use as an initial therapy was established in Guidelines for the Treatment of Childhood IgA nephropathy; however, no rescue therapy for recurrent or steroid-resistant pediatric IgAN was established.　We report here a 15-year-old boy with severe IgAN, who was treated with combination therapy involving prednisolone, mizoribine, warfarin, and dilazep dihydrochloride for 2 years.　The response to the combination therapy was good and both proteinuria and hematuria disappeared.　The pathological findings at the second renal biopsy were improved and PSL was discontinued.　However, due to nonadherence to the treatment regimen and tonsillitis, macrohematuria and an increase of proteinuria were again observed and the pathological findings at the third renal biopsy showed clear deterioration.　The patient was, therefore, diagnosed with recurrent IgAN.　Tonsillectomy plus methylprednisolone pulse therapy (TMP) was performed as a rescue therapy for the recurrence of severe IgAN.　Both the proteinuria or hematuria subsequently disappeared, and no proteinuria or hematuria has been observed and kidney function has remained normal during a 5-year follow-up.　The patient experienced no severe side effects associated with the drug regimens.　In conclusion, our case suggests that TMP may be an effective and useful rescue therapy for recurrent IgAN after multi-drug combination therapy.

Idiopathic Hyperammonemia That Developed During Initial Treatment With Steroid in a Patient With Newly Diagnosed Leukemia.

Idiopathic hyperammonemia (IHA) has been described as a complication of intensive chemotherapy for the treatment of hematologic malignancy but has subsequently been found in patients undergoing bone marrow transplantation and in those with solid tumors treated with 5-fluorouracil. Although IHA is a rare complication, it is sometimes associated with high mortality in hematologic malignancies. Here we report the case of a 15-year-old boy in whom hyperammonemia developed during the initial treatment with prednisolone for newly diagnosed acute lymphoblastic leukemia and who survived after early detection and oral lactulose therapy. To the best of our knowledge, this is the first report of IHA that was not induced by intensive chemotherapy, stem cell transplantation, or asparaginase therapy in a patient with newly diagnosed leukemia, but developed during an initial treatment with a steroid. Early detection of IHA by measuring the plasma ammonia level in patients with neurological symptoms may improve the outcome.