Background/Aim: Adult T-cell leukemia/lymphoma (ATLL) is a relatively refractory CD4-positive peripheral T-cell lymphoma. VCAP-AMP-VECP (mLSG15) is one of the standard chemotherapeutic regimens for patients with aggressive ATLL. Mogamulizumab (moga), a monoclonal antibody for CC chemokine receptor 4 antigen expressed on the cell surface, has recently been poised for use as monotherapy and in combination with chemotherapy. However, to date, a significant survival benefit has not been obtained with the combination of moga + mLSG15 therapy. Patients and Methods: We retrospectively analyzed 77 patients diagnosed with aggressive ATLL. Of them, 22 were treated with moga + a chemotherapy regimen comprised of etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisolone (EPOCH), 16 with moga + mLSG15, and 39 with chemotherapy alone. Results: A risk reduction of approximately 30% was obtained with moga + EPOCH compared with moga + mLSG15. Conclusion: The addition of moga to chemotherapy did not result in a survival benefit compared with chemotherapy alone. However, a statistically significant overall survival benefit was observed in patients with moga-induced skin disorders. The causative agent of adult T-cell leukemia/lymphoma (ATLL) is the retrovirus human T-cell lymphotropic virus type 1 (HTLV-1), which infects CD4-positive T-lymphocytes (1-3). HTLV-1 can be spread from mother to child during lactation, and the children become HTLV-1 carriers. HTLV-1 can also be spread from mother-to-child during birth as well as via blood transfusions, sexual contact, or sharing needles. Approximately 3%-5% of carriers develop ATLL after an incubation period of several decades. There are four clinical subtypes: acute, lymphoma, smoldering, and chronic (4). Patients suffering from acute, lymphoma, and chronic ATLL with bad prognostic factors are classified as aggressive ATLL. The prognosis of aggressive ATLL remains fairly poor despite intensive chemotherapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was found to cure patients with aggressive ATLL who obtained a complete response (CR) with first-line chemotherapy (5). Lenalidomide, an immunomodulating agent, and mogamulizumab (moga) have recently been poised for the treatment of aggressive ATLL (6, 7). However, no survival benefit has been observed in patients with aggressive ATLL treated with moga + VCAP-AMP-VECP (mLSG15) therapy, which is a standard chemotherapy treatment, compared with patients treated with mLSG15 therapy (8). Thus, the most suitable combination chemotherapy with moga must be urgently explored. Herein, we present the results of moga + a combination chemotherapy comprised of etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisolone (EPOCH). Patients and Methods Patients. We retrospectively analyzed 77 aggressive ATLL patients in our hospital, who were ineligible for allo-HSCT and diagnosed after June 2000. The data cutoff date for analyses was April 30, 2020. The patients were classified into three groups according to th...

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We present the case of a 78-year-old male patient who was diagnosed with anaplastic lymphoma kinase (ALK)-negative, CC chemokine receptor 4 (CCR4)-negative, and CD30-positive anaplastic large cell lymphoma (ALCL). The patient had a past medical history of adult T-cell leukemia/lymphoma and colon cancers that had developed simultaneously approximately 2 years prior to the development of ALCL that were treated with immunochemotherapy and resection, respectively. Initial treatment for ALCL included brentuximab vedotin, an anti-CD30 monoclonal antibody-monomethyl auristatin E conjugate; however, we were unable to achieve a sufficient treatment effect. Romidepsin, an oral histone deacetylase inhibitor, was introduced as salvage chemotherapy; complete remission was attained. Interestingly, a reversal of the CD4/CD8 ratio and a reduction in human T-lymphotropic virus type 1 (HTLV-1) virus load was observed after 2 cycles of immunochemotherapy; the patient experienced upregulation of HTLV-1 Tax-specific cytotoxic T lymphocytes after a herpes zoster infection and the completion of immunotherapy. The immunologic status was maintained from the time of diagnosis through the completion of romidepsin therapy. Our findings indicate that romidepsin can be used safely and effectively to treat ALCL without impairing cellular immunity to HTLV-1.

Herein, we present the case of a patient who suffered from adult T-cell leukemia/lymphoma (ATLL) and hepatocellular carcinoma (HCC) after obtaining a sustained virological response following treatment with a direct-acting antiviral (DAA) at different points in time. The patient went into complete remission (CR) for ATLL. Unfortunately, subsequent relapse of ATLL was observed. This situation was overcome using chemotherapy with pegylated interferon alpha-2b. Human T lymphotropic virus type 1 Tax-specific cytotoxic T lymphocytes (CTLs) were recognized after obtaining second CR, and those CTLs have been maintained for many years. After 4 years from the second CR, chronic hepatitis type C was treated with a DAA, and sustained virological response was attained. However, the occurrence of HCC was detected. Surprisingly, the tumor disappeared spontaneously. Hepatitis virus type C-specific CTLs were also detected in the patient. T-cell receptor (TCR) V beta gene repertoire analyses revealed oligoclonal expansion of effector and memory CTLs. The number of CTLs expressing the TCR V beta 13.1 has increased over the years since HCC occurrence. The activation and maintenance of anticancer cellular immunity may have allowed the patient to obtain long-term survival and overcome two lethal neoplasms.

This case report is about a patient who suffered from Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia. The blasts were positive for myeloid-lineage markers including CD13 and CD33, as well as B-cell-lineage markers. Minor bcr-abl1 mRNA was detected by real-time quantitative polymerase chain reaction. Chromosomal abnormality monosomy 7 was also observed, in addition to Ph1. Despite treatment difficulties that were anticipated based on these findings, the patient had long-time complete molecular response (CMR) for approximately 5 years using chemotherapy and two tyrosine kinase inhibitors, imatinib and dasatinib. Lymphocytes were elevated after the patient switched from imatinib to dasatinib, and a T-cell receptor (TCR) V beta gene repertoire analysis revealed oligoclonal expansion of effector and memory cytotoxic T lymphocytes (CTLs), including Wilms tumor 1-specific CTLs. More specifically, the two memory CTLs expressing TCR V beta 3 and V beta 7.1 gradually increased after dasatinib administration. The activation and maintenance of anti-leukemia immunity may have allowed the patient to obtain long-time CMR. These results highlight that obtaining memory CTLs for leukemia cells may lead to safe withdrawal from dasatinib in the patient.