Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T-cell leukemia–lymphoma: a comparative study of recurrent lesions after transplantation and chemotherapy by the Nagasaki Transplant Group
Abstract:Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients; however, the incidence of relapse associated with ATL remains high. To determine the clinical features of these patients at relapse, we retrospectively analyzed tumor lesions in 30 or 49 patients who relapsed following allo-SCT or chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture between 1997 and 2011. A multivariate analysis… Show more
“…14,15 In the discussion, we have considered and discussed why we did not provide allo-HSCT at the most appropriate timing antibody(inotuzumab) , 18 blinatumomab, 19 and CD19-CAR therapy; 20 those for AML, such as azacytidine(AZA) 21 or FMS-like tyrosine kinase 3(FLT 3)inhibitors; 22 and those for CML, such as tyrosine kinase inhibitors(TKIs) 23 Miyazaki prefecture, the OS of 40% after allo-HSCT treatment in 10 ATL cases was consistent with the findings of previous nationwide study [29][30][31] and previous endemic area reports from the Kyushu region in Japan. [32][33][34][35] Since the major cause of death after allo-HSCT was ATL relapse(6⊘6) , newer therapeutic agents such as C-C chemokine receptor type 4 (CCR4) a n t i b o d y a n d l e n a l i d o m i d e m a y b e n ove l t r e a t m e n t options. 36,37 In the present study, mogamulizumab was effective for the treatment of ATL in PB but was not effective for lymph nodes (LNS) lesions in ATL.…”
Background: The elucidation of clinical characteristics in deceased patients is essential to improve outcomes of hematopoietic stem cell transplantation(HSCT)for refractory/relapsed hematological malignancy. Patients and Methods: We retrospectively examined 81 refractory/relapsed hematological malignancy patients treated with allogeneic HSCT(allo-HSCT) (54)and autologous HSCT(auto-HSCT) (27)in our hospital from 2006 to 2016. Results: Consistent with previous Japan Marrow Donor Program annual reports, the overall survival(OS)rate of allo-HSCT and auto-HSCT patients were 59% and 84% at five years, respectively. Among patients receiving allo-HSCT, severe regimen-related toxicity(RRT) (grade≥3)events included cardiomyopathy due to cyclophosphamide(1) , idiopathic pulmonary syndrome(1) , acute graft-versus-host disease(GVHD)Ⅲ-Ⅳ(3) , acute-exacerbated chronic GVHD(2) , engraftment failure(2) , human herpesvirus-6 encephalitis(2) , and fungal infection(7). Moreover, univariate analysis identified disease risk index(DRI)and non-CR status before allo-HSCT as prognostic factors of OS. Among patients receiving auto-HSCT, the severe RRT event was thrombotic microangiopathy (1). The relapse after auto-HSCT in three patients with malignant lymphoma was a serious concern. Conclusion: Our study revealed critical issues in non-CR patients and those with high/very high DRI before allo-HSCT. Furthermore, the occurrence of severe RRT indicated the need for improvements in allo-and auto-HSCT.
“…14,15 In the discussion, we have considered and discussed why we did not provide allo-HSCT at the most appropriate timing antibody(inotuzumab) , 18 blinatumomab, 19 and CD19-CAR therapy; 20 those for AML, such as azacytidine(AZA) 21 or FMS-like tyrosine kinase 3(FLT 3)inhibitors; 22 and those for CML, such as tyrosine kinase inhibitors(TKIs) 23 Miyazaki prefecture, the OS of 40% after allo-HSCT treatment in 10 ATL cases was consistent with the findings of previous nationwide study [29][30][31] and previous endemic area reports from the Kyushu region in Japan. [32][33][34][35] Since the major cause of death after allo-HSCT was ATL relapse(6⊘6) , newer therapeutic agents such as C-C chemokine receptor type 4 (CCR4) a n t i b o d y a n d l e n a l i d o m i d e m a y b e n ove l t r e a t m e n t options. 36,37 In the present study, mogamulizumab was effective for the treatment of ATL in PB but was not effective for lymph nodes (LNS) lesions in ATL.…”
Background: The elucidation of clinical characteristics in deceased patients is essential to improve outcomes of hematopoietic stem cell transplantation(HSCT)for refractory/relapsed hematological malignancy. Patients and Methods: We retrospectively examined 81 refractory/relapsed hematological malignancy patients treated with allogeneic HSCT(allo-HSCT) (54)and autologous HSCT(auto-HSCT) (27)in our hospital from 2006 to 2016. Results: Consistent with previous Japan Marrow Donor Program annual reports, the overall survival(OS)rate of allo-HSCT and auto-HSCT patients were 59% and 84% at five years, respectively. Among patients receiving allo-HSCT, severe regimen-related toxicity(RRT) (grade≥3)events included cardiomyopathy due to cyclophosphamide(1) , idiopathic pulmonary syndrome(1) , acute graft-versus-host disease(GVHD)Ⅲ-Ⅳ(3) , acute-exacerbated chronic GVHD(2) , engraftment failure(2) , human herpesvirus-6 encephalitis(2) , and fungal infection(7). Moreover, univariate analysis identified disease risk index(DRI)and non-CR status before allo-HSCT as prognostic factors of OS. Among patients receiving auto-HSCT, the severe RRT event was thrombotic microangiopathy (1). The relapse after auto-HSCT in three patients with malignant lymphoma was a serious concern. Conclusion: Our study revealed critical issues in non-CR patients and those with high/very high DRI before allo-HSCT. Furthermore, the occurrence of severe RRT indicated the need for improvements in allo-and auto-HSCT.
“…The involved lesion was defined as previously reported 40,41 ; peripheral blood involvement was considered present when more than 5% of abnormal lymphocytes were detected by morphologically. 5,6,[25][26][27][28][29] The involvement of lymph nodes and extranodal lesions was based on confirmation by pathological findings.…”
Mogamulizumab (Mog) and lenalidomide (Len) are new therapeutic candidates for relapsed adult T‐cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). In the present study, we retrospectively analyzed 12 patients who received Mog or Len monotherapy for relapsed ATL after allo‐HSCT. Eight and three patients received Mog and Len, respectively. The remaining patient received Mog for the first relapse and Len for the third relapse. A complete response was achieved by three and two patients who received Mog and Len, respectively, two and one of whom remained alive with a complete response for more than 20 months. In terms of adverse events, the emergence or progression of graft‐versus‐host disease was observed in three out of four patients treated with Len and in none of the patients treated with Mog. The development or progression of cytomegalovirus reactivation was detected in four out of eight patients treated with Mog and in none of those treated with Len. The present results suggest that Mog and Len would be promising treatment options for relapsed ATL after allo‐HSCT and need to be selected based on adverse event profiles.
“…One of the characteristic features of adult T-cell leukemialymphoma (ATL) is its frequent multi-organ involvement (1,2). The clinical subtype of ATL is classified according to laboratory findings and the location of the tumor lesion (1).…”
A 53-year-old man was diagnosed with adult T-cell leukemia-lymphoma (ATL) acute type transformed from chronic type. A bone marrow analysis showed diffuse infiltration of abnormal lymphocytes and diffuse fibrotic change. He received unrelated cord blood transplantation (CBT) following reduced-intensity conditioning with complete remission of ATL after two courses of chemotherapy and achieved neutrophil and platelet engraftment. At 99 days after CBT, a bone marrow biopsy showed apparent resolution of myelofibrosis. These results suggest the therapeutic potential of CBT for patients with chemosensitive ATL with myelofibrosis.
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