Secondary Skin Cancer in a Case with Long-term Voriconazole after Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia.

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 In 2020, some lesions were diagnosed as squamous cell carcinoma, so voriconazole was withdrawn, and subsequent surgery and radiation led to remission.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.

Pharmacokinetics of anti-thymocyte globulin in a patient with severe aplastic anemia treated with allogeneic bone marrow transplantation from a matched unrelated donor.

Anti-thymocyte globulin (ATG) is an important component of preparative regimens for allogeneic bone marrow transplantation (BMT) for aplastic anemia (AA). However, the pharmacokinetics (PK) of ATG are unclear. A 38-year-old woman with severe AA underwent BMT using a fludarabine (Flu)-based and reduced-dose cyclophosphamide (CPA)-conditioning regimen comprising rabbit ATG (2.5 mg/kg, days -7 and -6), Flu (30 mg/sqm, days -5 to -2), CPA (25 mg/kg, days -5 to -2), and total body irradiation (2 Gy, day -1), following a human leukocyte antigen-match with an unrelated donor. Notably, ATG was administered earlier than that recommended by conventional schedules. The engraftment was achieved on day 15 without reactivation of the Epstein-Barr virus and residual recipient cells. Absolute lymphocyte recovery (>0.5×109/L) was achieved on day 22. The ATG concentration on day 0 and the area under the concentration-time curve (AUC) for ATG after allogeneic BMT were 21.8 µg/mL and 464 µg・day/mL, respectively. The patient remained disease-free for 6 years after BMT without acute or chronic graft-versus-host disease. Moreover, based on serum PK monitoring of ATG, including ATG concentration on day 0 and the AUC for ATG after BMT, the patient safely underwent the less-toxic, Flu-based, reduced-dose CPA regimen containing a low dose of ATG. In conclusion, we present the first report that analyzed the PK of ATG in a patient with AA treated with BMT from a matched unrelated donor. These findings might be helpful to determine ATG dosages for such patients receiving similar transplantations.

Three cases of late-onset anthracycline-related cardiomyopathy due to chemotherapies for hematological malignancy.

BACKGROUND: 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. METHODS: 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. RESULTS: All patients showed accumulation of anthracycline within a proper range (< 500 mg/sqm). Two patients (Hodgkin lymphoma and acute lymphoblastic leukemia) showed acute heart failure (AHF) with ejection fraction (EF) of 30 and 40% after 4.5 and 5 years after diagnosis, respectively. For AHF, diuretics and carperitide were administered to control in-out balance. The remaining patient (follicular lymphoma) showed ventricular fibrillation (VF)/ventricular tachycardia (VT) with EF of 40% at 5 years after diagnosis. In this patient, immediate cardioversion made VF/VT to normal sinus rhythm, and then, amiodarone was given. Furthermore, implantable cardioverter defibrillator was set up for VF/VT. In all patients, ß blocker and/or angiotensin-converting enzyme inhibitor (ACE-I) were administrated to prevent recurrence of anthracycline-related cardiomyopathy. Consequently, two of three patients showed mild improvement of cardiac function. CONCLUSION: Our study indicates that late-onset (4 to 5 years) anthracycline-related cardiomyopathy can develop, though range of anthracycline accumulation is in proper range. Thus, a cautious follow-up by ECG and UCG is required. Furthermore, the early treatment after the onset of anthracycline-related cardiomyopathy should be also needed to improve the poor outcome.

Clinical features and treatment outcomes of opportunistic infections among human T-lymphotrophic virus type 1 (HTLV-1) carriers and patients with adult T-cell leukemia-lymphoma (ATL) at a single institution from 2006 to 2016.

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.

Clinical Features, Pathological Features, and Treatment Outcomes of 22 Patients with Aggressive Adult T-cell Leukemia-lymphoma Treated with a Humanized CCR4 Antibody (Mogamulizumab) at a Single Institution during a 6-year Period (2012-2018).

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.

Successful treatment of adult Langerhans cell histiocytosis with intensified chemotherapy.

Langerhans cell histiocytosis (LCH) is a rare disease in adults. The treatment strategy for this condition remains controversial. Intensified systemic chemotherapy is required in pediatric patients with the multiple system form of LCH (MS-LCH) for aggressive forms of the disease. Recent clinical trials have shown that intensified chemotherapy for pediatric patients diagnosed with MS-LCH results in improved outcomes. However, whether the feasibility and efficacy of an intensified systemic chemotherapy regimen are also beneficial for adult patients with MS-LCH remains unclear. Here, we report two cases of adult MS-LCH that were successfully treated with an intensified treatment protocol as used in pediatric patients. One patient fully completed the protocol, and has since maintained a complete response (CR) for 2 years following completion of the treatment. The other patient also achieved CR after induction therapy, and is now undergoing maintenance therapy in an outpatient clinic. The cases presented in this study suggest that intensified systemic chemotherapy as used for pediatric patients with MS-LCH is well tolerated and effective for adult patients as well.