Naoto Fujita

Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric patients in Japan.

Reports of non‐anaplastic peripheral T‐cell lymphoma (PTCL) in pediatric patients are relatively rare.

Neurodegenerative central nervous system disease as late sequelae of Langerhans cell histiocytosis. Report from the Japan LCH Study Group

Langerhans’ cell histiocytosis can affect the central nervous system, where it frequently manifests as diabetes insipidus. Cerebellar ataxia and other neurological defects can represent late sequelae of this disorder. Clinical features, brain magnetic resonance imaging findings and EDSS scores of 11 patients with neurodegenerative central nervous system Langerhans cell histiocytosis were analyzed in Japan. All patients initially had multi-system-type Langerhans cell histiocytosis; 8 at 1–2 years of age and 3 at a later age. Neurodegenerative central nervous system largermans cell histiocytosis disease developed after a median time interval of 3.9 years from initial diagnosis. With a median follow-up of 4.5 years, 6 patients showed progression of disease with an EDSS score >3. This study demonstrates the importance of early detection of neurodegenerative central nervous system Langerhans cell histiocytosis by brain magnetic resonance imaging, particularly in the follow-up of patients who developed multi-system-type Langerhans cell histiocytosis in early infancy.

Reduced-intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis†

Familial hemophagocytic lymphohistiocytosis (FHL) is a disorder of immune homeostasis characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy. We studied the outcomes of 13 FHL patients who underwent the first unrelated cord blood transplantation (UCBT) after non‐myeloablative conditionings. The major regimen consisted of fludarabine (FLU; n = 12)+melphalan (MEL; n = 11)±low‐dose total body irradiation (TBI 2‐4 Gy; n = 6). The median age at presentation and period to UCBT were 6 and 5 months, respectively. Central nervous system (CNS) disease developed in one infant at diagnosis, and in two others until UCBT. HLH activity was controlled in all but one at the time of UCBT. Ten patients had early engraftment on median day 21 with no grade >2 treatment‐related toxicity and two controllable grade >2 acute GVHD. Two patients with early rejection successfully underwent subsequent UCBT after myeloablative conditioning. Two others had late graft failure following mixed donor chimerism. Two deaths occurred from HLH; early liver failure and late CNS disease. Of 11 FLU+MEL‐conditioned patients, the frequency of disease‐free complete engraftment was higher for MEL (≥120 mg/m2)+TBI, or high‐dose MEL (180 mg/m2) than for others (83% vs. 25%, p = 0.036). The FLU+MEL‐based non‐myeloablative regimen was acceptable for FHL infants undergoing UCBT, although further studies will be needed for confirmation. Am. J. Hematol. 87:637–639, 2012.

The role of hematopoietic stem cell transplantation with relapsed or primary refractory childhood B-cell non-Hodgkin lymphoma and mature B-cell leukemia: A retrospective analysis of enrolled cases in Japan

There have been excellent treatment results for children with B‐cell non‐Hodgkin lymphoma (B‐NHL) and mature B‐cell leukemia (B‐ALL) in the last few decades. However, a small subset of relapsed or refractory patients, after first‐line therapy, still have a poor prognosis.

Retrospective analysis of relapsed or primary refractory childhood lymphoblastic lymphoma in Japan

To assess the clinical course with response to second‐line treatment and to evaluate the role of hematopoietic stem cell transplantation (SCT) in children with relapsed or primary refractory lymphoblastic lymphoma (LBL), we analyzed data of 48 patients with relapsed/primary refractory diseases among 260 LBL patients identified in a national survey of 1996–2004.

Outcome of non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation from family donors in children and adolescents.

Non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (SCT) from family members has been reported, but its effectiveness and safety are not fully known. In this study, we examined the outcomes of 83 children and adolescents with nonmalignant (n = 11) or malignant (n = 72) disorders who underwent SCT mismatched at 2 or 3 HLA loci, either from the mother (n = 56), a noninherited maternal antigen (NIMA)-mismatched sibling (n = 14), or the father/a noninherited paternal antigen (NIPA)-mismatched sibling (n = 13). Engraftment was satisfactory. Severe (grade III-IV) acute graft-versus-host disease (GVHD) was noted only in malignant disease, with an incidence of 21 of 64 evaluable patients. GVHD prophylaxis with a combination of tacrolimus and methotrexate was significantly associated with a lower risk of severe acute GVHD, compared with other types of prophylaxis(P = .04). Nine of 11 patients with nonmalignant disease and 29 of 72 patients with malignant disease were alive at a median follow-up of 26 months (range, 4-57 months). Outcomes were not significantly different among the 3 donor groups (mother versus NIMA-mismatched sibling versus father/NIPA-mismatched sibling) for the malignancy disorders. Our results indicate that non-T-cell-depleted HLA-haploidentical SCT may be feasible, with appropriate GVHD prophylaxis, for young recipients who lack immediate access to a conventional stem cell source.

Stem cell transplantation for paediatric patients with non-anaplastic peripheral T-cell lymphoma in Japan

Reports of non‐anaplastic peripheral T‐cell lymphoma (PTCL) in paediatric patients, especially results of stem cell transplantation (SCT), are relatively rare. We herein report the results of SCT using the Transplant Registry Unified Management Program system of the Japanese Society of Stem Cell Transplantation in paediatric patients with non‐anaplastic PTCL. We analysed 26 patients (13 females and 13 males) aged ≤18 years with non‐anaplastic PTCL who underwent a total of 28 SCT. Median age at transplantation was 13·5 years (range: 0–18 years). PTCL not otherwise specified was diagnosed in 17 patients; extranodal Natural Killer (NK)/T cell lymphoma, nasal type in nine; and subcutaneous panniculitis‐like T‐cell lymphoma in two. Transplantation was with syngeneic donor in one, related donor in 10; unrelated donor in 10; and auto transplantation in 7. Five‐year overall survival rate and event‐free survival rate was 62·96% and 55·56%, respectively. Male gender, chronic graft‐versus‐host disease (GVHD), and reduced intensity conditioning were good prognostic factors in all patients. In 20 patients with refractory or relapsed disease, male gender and chronic GVHD were also good prognostic factors. This study is the first report concerning transplantation in children with non‐anaplastic PTCL, although the number of patients was small. Larger studies are needed to confirm these findings.

Empty sella/pituitary atrophy and endocrine impairments as a consequence of radiation and chemotherapy in long-term survivors of childhood leukemia

Radiation-induced empty sella (ES) or pituitary atrophy/small pituitary and endocrine impairments, including pituitary and gonadal dysfunction, can manifest decades after radiation and chemotherapy in childhood-onset leukemia patients who received prophylactic cranial irradiation or total body irradiation in preparation for bone marrow transplant. Six childhood-onset leukemia patients (age at diagnosis of leukemia; 2.7–10.2 years) participated in this study. Magnetic resonance imaging (MRI) of the pituitary gland and endocrinological studies were performed 10.5–32.1 years after cranial irradiation. In four of the six patients examined, ES or pituitary atrophy was detected approximately 10.5–19.8 years after cranial irradiation. Four patients had hypogonadism (primary, 3; hypothalamic-pituitary, 1) and one had primary hypothyroidism. We conclude that ES or pituitary atrophy and endocrine impairments can manifest decades after radiation and chemotherapy in childhood-onset leukemia. These patients should, therefore, undergo regular follow-up, including pituitary MRI and hormonal examinations.

Ring/marker chromosome derived from chromosome 7 in childhood acute megakaryoblastic leukemia with monosomy 7

In some cases of childhood acute megakaryoblastic leukemia (AMKL), G-band analysis reveals supernumerary ring/marker chromosomes along with monosomy 7. However, their origin and relevance are poorly understood. We experienced three patients with AMKL, one of whom had Down’s syndrome, whose blasts at the first visit exhibited both monosomy 7 and a ring/marker chromosome. For one case, precise molecular-cytogenetic techniques revealed that the ring chromosome was derived from a chromosome 7. It was strongly suggested that the ring chromosome was derived from a chromosome 7 in another case. The ring or one of the 2 marker chromosomes was derived from a chromosome 7 in the other case. All patients responded well to initial induction therapy. While it is not clear whether the ring/marker chromosome 7 affects the long-term prognosis of acute myeloid leukemia with monosomy 7, it may be of prognostic relevance to distinguish pure monosomy 7 from monosomy 7 with a ring/marker chromosome 7. For this purpose, conventional G-banding could be complemented with additional techniques such as spectral karyotyping or fluorescence in situ hybridization, which characterize the aberration in more detail. These methods may be useful for determining the optimal treatment and for elucidating the etiology of AMKL itself.

Prognostic impact of cytogenetic abnormalities in children and adolescents with mature B-cell non-Hodgkin lymphoma: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG)

Little information is available on cytogenetic abnormalities and their prognostic importance in childhood mature B‐cell non‐Hodgkin lymphoma (B‐NHL). We performed a review of 79 abnormal karyotypes in childhood B‐NHL treated by a uniform protocol. Del(17p) was independently associated with significantly inferior event‐free survival in Burkitt or Burkitt‐like lymphoma. The adverse prognosis of MYC/8q24 rearrangement, +7q or del(13q), was not observed, which had been suggested as risk factors in FAB/LMB96. Our results imply the possible existence of a biological difference among ethnicities and should be useful to narrow down the gene causing poor prognosis in childhood B‐NHL. Pediatr Blood Cancer 2015;62:1294–1296.