Late-onset noninfectious pulmonary complications (LONIPCs) occurring beyond 3 months after allogeneic stem cell transplantation (allo-SCT) have become recognized as life-threatening complications, and they reduce the recipient9s quality of life. However, the pathogenesis and optimal treatment for LONIPCs are still unclear. In this study, we retrospectively analyzed the incidence and outcome of LONIPCs among allo-SCT recipients. Between October 1993 and September 2001, 96 patients underwent allo-SCT and 76 patients who survived and were free of disease for more than 3 months after SCT were enrolled. Among the 76 patients, 18 patients (23.7%) developed LONIPCs at a median interval of 227 days after allo-SCT (range, 91-1105 days). The patients with LONIPCs were subclassified into those with bronchiolitis obliterans (BO) (6 patients), with interstitial pneumonia (IP) (11 patients), or with both BO and IP (1 patient). The presence of extensive chronic graft-versus-host disease (GVHD) was significantly associated with the development of LONIPCs (P = .0008). Liver or skin involvement in chronic GVHD was not associated, but sicca syndrome was significantly associated with the development of LONIPCs (P < .0001). Most of the IP patients (58.3%) responded well to immunosuppressive treatment, while BO patients did not respond to the therapy. Eight of the 18 patients with LONIPCs died. The major cause of death was respiratory failure (62.5%). The relapse rate of primary malignant disease in the LONIPC patients was significantly lower than that of non-LONIPC patients (1 of 17 [5.9%] versus 16 of 52 [30.8%]; P = .0387). These results indicate that the development of LONIPCs was strongly associated with chronic GVHD and especially with sicca syndrome and the graft-versus-leukemia (GVL) effect. (Blood. 2003;102:4236-4242)

The muscle-related complications of fasciitis and myositis, caused by chronic GVHD after Allo-SCT are relatively rare, but at times will severely impair a patient's quality of life (QOL). We performed a retrospective analysis in Japanese Allo-SCT recipients to identify the incidence, risk factors and clinical features of fasciitis and myositis. In 1967 patients who underwent Allo-SCT between January 1994 and March 2005 and survived beyond 90 days post transplantation, eight patients developed fasciitis and nine patients developed myositis, with a 5-year cumulative incidence of 0.55% and 0.54%, respectively. The median time from SCT to the development of fasciitis and myositis was 991 and 660 days, respectively. PBSCT was a risk factor for developing fasciitis, but no risk factors were found for myositis. The response to immunosuppressive treatment was better in patients with myositis than fasciitis, and the overall survival after developing these symptoms was better in patients with myositis than those with fasciitis. An early diagnosis by a biopsy, which includes fascia and muscle or magnetic resonance imaging (MRI) and prompt treatment may be important to prevent an impairment of the patient's QOL with persistent disability.

Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1–17). Age, hemoglobin concentration and white blood cell counts were correlated with the number of mutations. Patients with mutations ⩾6 showed higher rate of achieving major molecular response than those<6 (P=0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6 were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one patient each. ASXL1 was mutated within exon 12 in three cases. Mutated genes were significantly enriched with cell signaling and cell division pathways. Furthermore, DNA copy number analysis showed that 2 of 24 patients had uniparental disomy of chromosome 1p or 3q, which disappeared major molecular response was achieved. These mutations may play significant roles in CML pathogenesis in addition to the strong driver mutation BCR-ABL1.

We retrospectively reviewed 413 recipients with hematologic malignancies who underwent hematopoietic stem cell transplantation (HSCT) between June 1986 and March 2013. Recipients with antibody to hepatitis B core antigen (anti-HBc) and/or to hepatitis B surface antigen (anti-HBs) were regarded as experiencing previous hepatitis B virus (HBV) infection. Clinical data of these recipients were reviewed from medical records. We defined ≥1 log IU/mL increase in serum HBV DNA from nadir as HBV reactivation in hepatitis B surface antigen (HBsAg)-positive recipients, and also defined ≥1 log IU/mL increase or re-appearance of HBV DNA and/or HBsAg as HBV reactivation in HBsAg-negative recipients. In 5 HBsAg-positive recipients, 2 recipients initially not administered with nucleos(t)ide analogues (NUCs) experienced HBV reactivation, but finally all 5 were successfully controlled with NUCs. HBV reactivation was observed in 11 (2.7%) of 408 HBsAg-negative recipients; 8 of these were treated with NUCs, and fortunately none developed acute liver failure. In 5 (6.0%) of 83 anti-HBc and/or anti-HBs-positive recipients, HBV reactivation occurred. None of 157 (0%) recipients without HBsAg, anti-HBs or anti-HBc experienced HBV reactivation. In HSCT recipients, HBV reactivation is a common event in HBsAg-positive recipients, or in HBsAg-negative recipients with anti-HBc and/or anti-HBs. Further attention should be paid to HSCT recipients with previous exposure to HBV.