GvATLL Effect in the Relapse and Progression Cases After Hematopoietic Stem Cell Transplantation (HSCT) for Adult T-Cell Leukemia/Lymphoma (ATLL).
Authors: Nakano Nobuaki , Kubota Ayumu , Tokunaga Mayumi , Tokunaga Masahito , Takeuchi Shogo , Takatsuka Yosifusa , Utsunomiya Atae 
Published: October 2019

Abstract
Abstract 4299

Background
Adult T-cell leukemia/lymphoma (ATLL) has a poor prognosis because of its chemo-resistance. Many chemotherapeutic regimens have been created but none of them have shown sufficient results. We proposed allogeneic stem cell transplantation (allo-SCT) for ATLL patients and showed an improved survival rate. However, relapse or progression of ATLL is one of the major limiting factors of survival in post SCT patients.

Aims
In order to establish a better treatment strategy for poor responders after SCT for ATLL, we analyzed the outcome of relapse or progression cases after allo-SCT. We paid special attention to the graft versus ATLL (GvATLL) effect.

Methods
There were 37 ATLL patients in which allo-SCT was performed in Imamura Bun-in Hospital (IBH) from June 1998 to April 2009. Twenty-eight cases survived over 100 days after SCT. Sixteen of the 30 patients relapsed. Using data in medical records of IBH, we analyzed transplant characteristics and the outcome of these 17 patients retrospectively.

Results
Disease status at SCT was CR in 2 patients, 2 PR, 5 SD, and 7 PD. Eight patients received conventional stem cell transplantation (CST) and the other seven patients received reduced-intensity stem cell transplantation (RIST). Fourteen patients in 17 obtained remission (10 CR and 5 PR), but the remaining 2 did not (1 SD and 1 PD) after SCT. The sites of relapse or progression in 17 were skin in 10 patients, 8 peripheral blood, 7 lymph node, 3 central nervous system, and 1 bone. All patients discontinued immunosuppressants after relapse or progression. Eleven patients obtained remission. Especially, in 5 out of 11 patients, remission was obtained only by discontinuation of immunosuppressants (graft-versus-ATLL effect), and the time to remission after discontinuation of immunosuppressants was between 1 to 14 days. Twelve patients were complicated with acute GVHD (grade I-IV). Twelve patients died after SCT. The causes of death were disease progression of ATLL in 5 patients, 3 acute GvHD, 3 infectious complications, and 1 interstitial pneumonia. Four patients who were complicated with acute GvHD survived over 3 years.

Discussions
Ten patients out of 17 experienced relapse or progression as skin lesion, and 8 patients out of 10 achieved re-remission. It suggests that skin lesion can be a warning sign of ATLL relapse. Since various types of clinical entities, such as ATLL relapse, GvHD, or drug eruption, can manifest as skin lesion after SCT, we strongly recommend to do skin biopsy aggressively to clarify the diagnosis. Ten patients out of 17 achieved re-remission (5 of them achieved only after the discontinuation of immunosuppressant), and 2 patients out of 5 attained long-term survival. This fact raises the possibility that GvATLL effect play a role in controlling exacerbation of ATLL. By focusing on the 5 cases that obtained re-remission only with discontinuation of immunosuppressant, 4 cases showed GvATLL effect prior to GvHD, and one patient experienced fatal grade IV GvHD, respectively. These outcomes suggest that immunosuppressant should be resumed in response to the signs of GvHD deterioration. Relapse/progression cases shows poor survival rate compared with non-relapse ones (60% vs 20% P=0.0028). Although re-remission was highly achieved, this fact suggested that countermeasure against GvHD or re-relapse are indispensable for long-term survival.

Summary/conclusions
Skin was a major site of relapse or progression after SCT in ATLL patients. A certain number of patients obtained remission only by the discontinuation of immunosuppressants. Four patients survived more than 3 years with their complication of acute GVHD. These results suggest that the GvATLL effect after SCT exists and plays an important role in longer survival for poor responders of post allo-SCT in ATLL patients.

Disclosures:
No relevant conflicts of interest to declare.