Progress in Allogeneic Hematopoietic Cell Transplantation in Adult T-Cell Leukemia-Lymphoma

Abstract

The prognosis of aggressive adult T-cell leukemia-lymphoma (ATL) remains poor because of frequent infections and drug resistance. Dose-intensified chemotherapy followed by autologous stem cell transplantation failed to improve the prognosis of patients with ATL; however, we first revealed that allogeneic hematopoietic cell transplantation (allo-HCT) might improve their prognosis. We showed that reducedintensity stem cell transplantation using peripheral blood was feasible for elderly patients. Further, the prognosis of patients in remission, who receive cord blood transplantation, has been recently improved and is equivalent to that of patients who receive transplants from other stem cell sources. As for the timing of HCT, the patients who underwent transplantation early showed better outcomes than those who underwent transplantation late. Based on the analysis of patients with aggressive ATL, including those who received transplants, we identified five prognostic factors for poor outcomes: acute-type ATL, poor performance status, high soluble interleukin-2 receptor levels, hypercalcemia, and high C-reactive protein level. Next, we developed a new prognostic index: the modified ATL-PI. The overall survival (OS) rates were significantly higher in patients who underwent allo-HCT than those who did not in the intermediate and high-risk groups stratified using the modified ATL-PI. Two new anti-cancer agents, mogamulizumab and lenalidomide, were recently approved for ATL patients in Japan. They are expected to induce longer survival in ATL patients when administered along with transplantation. However, a retrospective analysis that the risk of severe, acute, and corticosteroid-refractory graft-versus-host disease was higher in patients who received mogamulizumab before allo-HCT, and that mogamulizumab might increase the transplant-related mortality (TRM) rates and decrease the OS rates compared to those of patients who did not receive mogamulizumab. However, our recent study showed that administration of mogamulizumab before allo-HCT tended to improve the survival of patients with ATL. In conclusion, allo-HCT procedures for patients with aggressive Frontiers in Microbiology | www.frontiersin.org October 2019 | Volume 10 | Article 2235 Utsunomiya Allo-HCT in ATL ATL have considerably progressed and have helped improve the prognosis of these patients; however, many concerns still remain to be resolved. Further development of allo-HCT by using new molecular targeting agents is required for the improvement of cure rates in patients with ATL.

Pathologically Proven Intraocular Infiltration With Adult T-Cell Leukemia/Lymphoma: Two New Cases With Either Vitreous Opacity or Aqueous Hypopyon and Literature Review of 16 Cases

“…In the second patient of the present study, hypopyon appeared after allogeneic HSCT, which is the current standard treatment in relapse after chemotherapy for ATLL. 24 Hypopyon was easily diagnosed clinically as relapse of ATLL. With pathological diagnosis of aqueous aspirate as class V, the patient underwent additional chemotherapy combined with mogamulizumab as the current standard therapy.…”

How I treat adult T-cell leukemia/lymphoma

“…The European Group for Blood and Marrow Transplantation's (EBMT) Lymphoma Working Party has confirmed alloSCT may also salvage ATL patients 37 . Outside of Japan however, it can be difficult to find suitably matched donors since the majority of cases arise in ethnic minorities not reflective of transplant donor registries, with family members often living overseas, and with the added complication of HTLV-1 infected siblings 38 . If the only available donor is HTLV-1 positive, we would assess the donor for clonal expansions (PVL and an assay for HTLV-1 clonal expansion 39 ) and if the donor is low risk we would proceed.…”

Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

“…We first reported the possibility that allogeneic (allo) hematopoietic cell transplantation (HCT) using myeloablative conditioning (MAC) may improve the outcome of patients with aggressive ATL [29]. Afterward, many methods of allo-HCT for patients with ATL using reduced-intensity conditioning, peripheral blood stem cells, and cord blood were developed by Japanese researchers [30][31][32][33]. Furthermore, HLA-haploidentical HCT was performed in patients with ATL who did not have HLA-matched suitable donors [34].…”

“…Although OS rates of patients with ATL are not so high, allo-HCT is regarded as the only curative treatment for aggressive ATL in Japan at the present time. Furthermore, allo-HCT is thought to be the curative treatment in many countries other than Japan [33,36,37]. Recently, two new molecular targeting agents have been approved for aggressive ATL in Japan.…”