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Donor lymphocyte infusion (DLI) is a therapeutic modality for relapsed hematological malignancies after allogeneic hematopoietic stem cell transplantation. We retrospectively analyzed non-infectious pulmonary complications (non-IPCs) following DLI therapy in 41 post-transplant patients with hematological malignancies, and found that 7 developed post-DLI non-IPCs. The 6-year cumulative incidence of non-IPCs was 18.0%. In these patients, non-IPCs were classified into three subtypes: acute respiratory distress syndrome (ARDS), nonspecific interstitial pneumonia (NSIP), and bronchiolitis obliterans syndrome (BOS). The median intervals from the last date of DLI to the development of ARDS and BOS were 12 days (range, 12–14) and 9.4 months (range, 2.6–61.8), respectively; the intervals between DLI and the development of NSIP were 3.5 and 24.7 in 2 patients. Regarding the status of GVHD before the diagnosis with ARDS, 2 out of 3 patients showed the progression of acute GVHD following DLI therapy. One out of 2 patients with NSIP and all 3 patients with BO had chronic GVHD symptoms prior to the development of non-IPCs. In our cohort, 1 patient died of the progression of NSIP. In conclusion, the present study showed the clinical features of non-IPCs following DLI, suggesting the importance of careful followups for non-IPCs in post-DLI patients., Transplant Immunology, 75, art. no. 101707; 2022

Donor lymphocyte infusion (DLI) is a therapeutic modality for relapsed hematological malignancies after allogeneic hematopoietic stem cell transplantation. We retrospectively analyzed non-infectious pulmonary complications (non-IPCs) following DLI therapy in 41 post-transplant patients with hematological malignancies, and found that 7 developed post-DLI non-IPCs. The 6-year cumulative incidence of non-IPCs was 18.0%. In these patients, non-IPCs were classified into three subtypes: acute respiratory distress syndrome (ARDS), nonspecific interstitial pneumonia (NSIP), and bronchiolitis obliterans syndrome (BOS). The median intervals from the last date of DLI to the development of ARDS and BOS were 12 days (range, 12–14) and 9.4 months (range, 2.6–61.8), respectively; the intervals between DLI and the development of NSIP were 3.5 and 24.7 in 2 patients. Regarding the status of GVHD before the diagnosis with ARDS, 2 out of 3 patients showed the progression of acute GVHD following DLI therapy. One out of 2 patients with NSIP and all 3 patients with BO had chronic GVHD symptoms prior to the development of non-IPCs. In our cohort, 1 patient died of the progression of NSIP. In conclusion, the present study showed the clinical features of non-IPCs following DLI, suggesting the importance of careful followups for non-IPCs in post-DLI patients., Transplant Immunology, 75, art. no. 101707; 2022

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment., identifier:Leukemia Research, 38(1), pp.76-83; 2014

A 62-year-old male was diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN) with a MYC rearrangement. Four months after the first unrelated bone marrow transplantation (BMT), he developed the relapsed BPDCN. After the achievement of partial remission following re-induction therapy, he underwent a second BMT from another unrelated donor, and experienced complete remission with grade II acute graft-versus-host disease and moderate chronic graft-versus-host disease. He remains alive in complete remission more than 71 months after the second BMT. These results suggested that donor change at the second transplantation may represent a considerable therapeutic option for patients with relapsed BPDCN., Leukemia Research Reports, 11, pp.31-33; 2019

Myeloperoxidase (MPO) has been associated with both a myeloid lineage commitment and favorable prognosis in patients with acute myeloid leukemia (AML). DNA methyltransferase inhibitors (decitabine and zeburaline) induced MPO gene promoter demethylation and MPO gene transcription in AML cells with low MPO activity. Therefore, MPO gene transcription was directly and indirectly regulated by DNA methylation. A DNA methylation microarray subsequently revealed a distinct methylation pattern in 33 genes, including DNA methyltransferase 3 beta (DNMT3B), in CD34-positive cells obtained from AML patients with a high percentage of MPO-positive blasts. Based on the inverse relationship between the methylation status of DNMT3B and MPO, we found an inverse relationship between DNMT3B and MPO transcription levels in CD34-positive AML cells (P=0.0283). In addition, a distinct methylation pattern was observed in five genes related to myeloid differentiation or therapeutic sensitivity in CD34-positive cells from AML patients with a high percentage of MPO-positive blasts. Taken together, the results of the present study indicate that MPO may serve as an informative marker for identifying a distinct and crucial DNA methylation profile in CD34-positive AML cells., Leukemia, 28(7), pp.1459-1466; 2014

Although allogeneic hematopoietic stem cell transplantation (allo-SCT) is performed as a curative option in adult T cell leukemia-lymphoma (ATL) patients, its high transplantation-related mortality raises a serious issue. The clinical features of infectious complications after transplantation are not well known. To analyze the impact of infections after allo-SCT for ATL, we retrospectively compared infectious complications in 210 patients at 3 institutions in Nagasaki prefecture between 1997 and 2009. There were 91 patients with acute myeloid leukemia (AML), 51 with acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL), and 68 with ATL. No patient received ganciclovir or foscarvir as prophylaxis, and most patients received antifungal prophylaxis with fluconazole or itraconazole. The cumulative incidence of cytomegalovirus (CMV) infection at 3 years was 69.2% in ATL patients versus 54.4% in AML patients (P = .0255). Cumulative infection-related mortality was significantly higher in ATL patients than in the 2 other groups (ATL versus AML, P = .0496; ATL versus ALL/LBL, P = .0075), and most death-causing pathogens were bacteria and fungus. The appearance of CMV infection was negatively associated with infectious mortality in ATL patients, but the P value for this association was near the borderline of significance (P = .0569). In multivariate analysis, transplantation using unrelated bone marrow and episodes of CMV infection were associated with worse overall survival in ATL patients, but were not in either AML or ALL/LBL patients. Collectively, the impact of infectious complications after transplantation in ATL patients was different from that in AML and ALL/LBL patients, suggesting that a more intensive strategy for infection control in ATL patients is required to reduce infectious mortality., Biology of Blood and Marrow Transplantation, 19(4), pp.607-615; 2013

Erratum to: International Journal of Hematology, 94(1), pp.81-89: 2011 DOI 10.1007/s12185-011-0883-y The original version of this article unfortunately contained some errors in Table 2 in the column headed ‘‘Amino acid changes’’. The corrected table is given here., International Journal of Hematology, 96(2), pp.291-292; 2012

The percentage of myeloperoxidase (MPO)-positive blast cells is a simple and highly significant prognostic factor in AML patients. It has been reported that the high MPO group (MPO-H), in which >50% of blasts are MPO activity positive, is associated with favorable karyotypes, while the low MPO group (≤50% of blasts are MPO activity positive, MPO-L) is associated with adverse karyotypes. The MPO-H group shows better survival even when restricted to patients belonging to the intermediate chromosomal risk group or those with a normal karyotype. It has recently been shown that genotypes defined by the mutational status of NPM1, FLT3, and CEBPA are associated with treatment outcome in patients with cytogenetically normal AML. In this study, we aimed to evaluate the relationship between MPO positivity and gene mutations found in normal karyotypes. Sixty AML patients with normal karyotypes were included in this study. Blast cell MPO positivity was assessed in bone marrow smears stained for MPO. Associated genetic lesions (the NPM1, FLT3-ITD, and CEBPA mutations) were studied using nucleotide sequencing. Thirty-two patients were in the MPO-L group, and 28 patients in the MPO-H group. FLT3-ITD was found in 11 patients (18.3%), NPM1 mutations were found in 19 patients (31.7%), and CEBPA mutations were found in 11 patients (18.3%). In patients with CEBPA mutations, the carrying two simultaneous mutations (CEBPA (double-mut)) was associated with high MPO expression, while the mutant NPM1 without FLT3-ITD genotype was not associated with MPO activity. Both higher MPO expression and the CEBPA (double-mut) genotype appeared to be associated with improved overall survival after intensive chemotherapy. Further studies are required to determine the importance of blast MPO activity as a prognostic factor, especially in CEBPA wild-type patients with a normal karyotype., International Journal of Hematology, 94(1), pp.81-89: 2011

A 26-year-old female diagnosed as mycosis fungoides (MF, clinical stage IV) was treated with single-agent chemotherapy, multi-drug chemotherapy and unrelated bone marrow transplantation with reduced-intensity conditioning (engraftment failure), resulting in failure. Unrelated cord blood transplantation (CBT) as second transplantation following myeloablative conditioning brought complete remission (CR), but relapse of MF occurred 3 months after transplantation. However, discontinuation of immune suppressant led to the regression of MF regions and to second CR that continued for more than 23 months. This is the first report of successful CBT for MF, suggesting the graft-versus-MF effect in a setting of CBT., The original publication is available at www.springerlink.com, International Journal of Hematology, 88(5), pp. 596-598; 2008