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Secondary malignancies that develop after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) have become serious issues. A 47-year-old man who developed acute myeloid leukemia in 2009 and subsequently underwent allo-HSCT twice: in 2009 and 2011. In 2015, voriconazole for lung aspergillus was started. In 2018, chronic graft-versus-host disease (GVHD) and multiple actinic keratoses manifested at his head. In 2020, some lesions were diagnosed as squamous cell carcinoma, so voriconazole was withdrawn, and subsequent surgery and radiation led to remission. Long-term administration of voriconazole in addition to allo-HSCT and chronic GVHD may be closely related to secondary skin cancer.

Although tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), intolerance and resistance to TKIs have been serious problems. Due to a lack of research, the importance of the pharmacokinetics (PK) of TKIs is currently unclear. We examined the PK of the third-generation TKI ponatinib to monitor side effects and efficacy during treatments for one patient with CML-chronic phase (CP-CML) and two who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), one for CML-blastic crisis (BC-CML) and one for Ph + ALL. The patient with CP-CML was intolerant to multiple TKIs (dasatinib, nilotinib, imatinib, and bosutinib) and thus was switched to ponatinib (15 mg/day). The patients who received allo-HSCT for BC-CML and Ph + ALL received ponatinib (15 mg/day) as maintenance therapy. Notably, serial evaluation of the PK of ponatinib showed that the median trough values (ng/ml) were 17.2 (12.2-34.5), 33.1 (21.2-40.3) and 27.7 (13.6-29.9) in patients 1, 2, and 3, respectively. These values were around the target concentration (23 ng/ml). All patients are maintaining complete remission without side effects. In conclusion, serial evaluation of PK of ponatinib may yield meaningful information about its safety and efficacy.

The relapse of acute lymphoblastic leukemia (ALL) usually involves the bone marrow, with the central nervous system being the most frequent extramedullary site. The relapse of ALL in the female genital organs, particularly the uterus, is markedly rare. We report such a patient who developed relapse in the bone marrow and uterus. The uterine lesion, which presented as abnormal uterine bleeding, consisted of a mass on MRI and proliferation of ALL cells on histology. MRI revealed a heterogeneous high-intensity mass (T2-WI/D-WI) with a diameter of 6.8 cm, a notable decrease in the apparent diffusion coefficient (ADC), and mild enhancement by contrast enhancement study. Histological findings of the uterine cervix demonstrated the infiltration of ALL. The patient achieved remission by allogeneic haplo-identical hematopoietic stem-cell transplantation, but died of complications of the transplantation. This case suggested that attention should be paid to the uterus as a site of extramedullary relapse. In addition, abnormal uterine bleeding, which is a common sign of hormonal imbalance and hormone replacement therapy after chemotherapy, may be an initial sign of extramedullary recurrence. To confirm uterine relapse as an intractable disease, the accumulation of more cases is required.

Objective To elucidate the clinical impact of humanized CCR4 antibody (mogamulizumab) on adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed the clinical and pathological features and treatment outcomes of aggressive ATL. Methods Twenty-two patients (median age: 65 years) with aggressive ATL [acute- (n=16) or lymphoma-type (n=6)] had their characteristics analyzed. All cases were treated with mogamulizumab at our institution from 2012 to 2018. In addition, we subjected 14 specimens of ATL to histological, immunological, and genetic analyses. Results Regarding the patient outcomes, the overall response rates were 68.1% and 31.8% after 4 and 8 courses (or after the final courses), respectively. The median overall survival (OS) was 95.5 days, while the OS rates at 6 and 12 months were 31.5% and 21.1%, respectively. Concerning patient pathological characteristics, 6 of the 14 patients examined (42.9%) had CCR4 mutations. Regarding the clinicopathological findings related to the mogamulizumab response, notably, the cases with somatic CCR4 mutation tended to have a poorer response (16.7%) than those with wild-type CCR4 (62.5%) after 4 cycles of mogamulizumab. Furthermore, the CCR4 global score tended to be higher in the responder cases than in the non-responder cases. Conclusion The present findings suggest that the CCR4 expression may be related to the mogamulizumab response, although no other significant predictive markers were identified in this study. Further studies will be needed in order to identify more markers related to the mogamulizumab response.

As opportunistic infections among human T-lymphotrophic virus type 1 (HTLV-1) carriers and patients with adult T-cell leukemia/lymphoma (ATL) pose a serious problem, it is necessary to clarify their clinical characteristics and outcomes in these patients. We retrospectively analyzed the clinical features and outcomes of opportunistic infections in 127 HTLV-1 carriers and 153 ATL patients between 2006 and 2016. The cumulative incidence rates of opportunistic infections among HTLV-1 carriers and ATL patients were 1.5% (2/127) and 6.5% (10/153), respectively. The etiology of opportunistic infections was as follows: fungal infections (3 cases), pneumocystis pneumonia, and cytomegalovirus (CMV) infections. Even after aggressive treatment, the prognosis of opportunistic infections was poor (50% of overall survival at 28 days). Regarding prognostic factors affecting the OS of opportunistic infections, higher SOFA scores (especially the respiratory subscore) and higher LDH values were identified by univariate analysis. Moreover, 3 out of 6 patients achieved spontaneous remission of ATL as the short-term outcome after the development of opportunistic infection. However, 5 out of 6 surviving patients exhibited ATL progression or relapse after a median of 194 days (133-226) after contracting an opportunistic infection as the long-term outcome of ATL. In conclusion, opportunistic infections should be carefully followed among HTLV-1 carriers and ATL patients because of their aggressive clinical course and poor outcomes. Furthermore, early diagnosis and subsequent prompt treatment are necessary in clinical practice.

Although anthracycline-related cardiomyopathy is a life-threatening complication during intensive treatment for hematological malignancies, clinical features and outcomes of this type of cardiomyopathy have been unclear because of limited reports in the literature. We analyzed three cases of anthracycline-related cardiomyopathy among 996 patients with either acute myelogenous leukemia (285), acute lymphoblastic leukemia (37), or malignant lymphoma (674) at our hospital during the period from 2006 to 2016. All patients showed accumulation of anthracycline within a proper range (

Advanced-stage mycosis fungoides (MF) has a generally poor prognosis. Allogeneic hematopoietic stem cell transplantation improves the outcome of advanced-stage MF. Recently, cord blood has been used as an alternative stem cell source; however, there are few reports of MF patients treated using cord blood transplantation. Here, we report a rare case of refractory folliculotropic MF, which was treated with reduced-intensity conditioning followed by cord blood transplantation.

We present the case of a 62-year-old Japanese woman with relapsed adult T-cell leukemia/lymphoma (ATLL) who was treated with humanized anti-CCR4 monoclonal antibody (KW-0761). Although this antibody was highly effective against refractory ATLL, 6 months after the final KW-0761 infusion, the patient complained of hypoxia due to diffuse panbronchiolitis. Physicians should remain vigilant to the possibility of such previously unreported late-onset adverse effects associated with KW-0761 therapy.

A 76-year-old man suffered from swelling stoma for several weeks. A biopsy sample revealed the diffuse infiltration of large lymphoid cells which were positive for CD20, bcl-6, and MUM1. The patient was diagnosed with diffuse large B-cell lymphoma, with a non-germinal center B-cell pattern. A whole-body PET-CT scan revealed that the lymphoma was restricted to the stomal site. Bladder reconstruction was undertaken using the ileal conduit: this is the first reported case of lymphoma that developed primarily at the stoma. During the long-term maintenance after bladder reconstruction, clinicians should consider the possibility of lymphoma at the stomal site.