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 revealed that the development of abnormal lymphocytes in the peripheral blood of patients at relapse was less frequent after allo-SCT than after CHT (P<0.001). Furthermore, relapse with a new lesion only in the absence of the primary lesion was more frequent in allo-SCT (P=0.014). Lesions were more frequently observed in the central nervous systems of patients who relapsed with new lesions only (P=0.005). Thus, the clinical manifestation of relapsed ATL was slightly complex, especially in post-transplant patients. Our results emphasized the need to develop adoptive modalities for early and accurate diagnoses of relapsed ATL.
Adult T-cell leukemia–lymphoma (ATL) is a peripheral T-lymphocytic neoplasm that is caused by human T-cell lymphotropic virus type I (HTLV-1).1 One of the characteristic features of ATL is its frequent multiorgan involvement, which has been implicated in the poor prognosis of patients with ATL. Lymphadenopathy, hepatomegaly, splenomegaly, as well as skin, pulmonary and central nervous system (CNS) lesions, and 5% or more abnormal T lymphocytes in the peripheral blood have been reported in most cases of ATL. The clinical manifestation of ATL is heterogeneous and is characterized by this organ involvement, which has been used to classify the disease into four subtypes: acute, lymphoma, chronic and smoldering.2
ATL is resistant to various cytotoxic agents and has a poor prognosis.3, 4 Allogeneic hematopoietic SCT (allo-SCT) for patients with aggressive ATL (acute, lymphoma and the unfavorable chronic type) is considered to be a therapeutic option that can provide apparent durable remission along with graft-vs-ATL effects.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 However, both the relapse rate and TRM after allo-SCT were previously shown to be high, and are urgent issues that need to be addressed.9, 19, 20 Previous studies, including ours, raised the possibility that patients with local relapse may achieve long-term remission by local cytoreductive therapy alone, and that those with skin recurrence (i.e. non-aggressive disease) could benefit from DLI.21, 22 These findings implied that an intervention for the residual disease at the early phase may improve the outcomes of ATL patients; however, a standard method to monitor the residual disease after remission has not yet been established. Moreover, very few studies have examined the clinical manifestation of relapsed ATL by carefully analyzing an adequate number of cases. Identifying the clinical characteristics of ATL at relapse is important for establishing an adoptive monitoring strategy. In the present study, we retrospectively analyzed 30 and 49 ATL patients who relapsed after allo-SCT and chemotherapy (CHT), respectively, at three institutes in Nagasaki prefecture.
Patients and Methods
We conducted a retrospective survey of patients diagnosed with aggressive ATL2 who received initial systemic CHT at three hospitals in Nagasaki prefecture between 1 April 1997 and 31 March 2011. The unfavorable chronic type of ATL was defined according to previous criteria.4 The diagnosis of ATL was based on clinical features, histologically and/or cytologically proven mature T-cell malignancy, the presence of the anti-HTLV-1 Ab and the monoclonal integration of HTLV-1 original DNA into tumor cells, as described previously.2, 23, 24 A total of 336 patients were excluded from the 497 patients whose data were available because they did not achieve CR after CHT or allo-SCT (Figure 1). CHT and transplant procedures were performed according to the decision of the clinicians at each center. The intrathecal administration of CHT as prophylaxis for CNS relapse was performed based on the decision of clinicians before 2007, and was then routinely performed after 2007 as described previously in a phase III clinical trial for aggressive ATL.4 No patient received mogamulizumab before achieving the first CR. Relapse after the first CR was observed in 79 of the remaining 161 patients, and these patients were included in this analysis. Data on the 79 patients were collected and updated as of July 2013. This study was approved by the Ethical Committee of each participating hospital.
Performance status was based on the 5-grade scale of the Eastern Cooperative Oncology Group. Because HTLV-1 carriers frequently have a small percentage of abnormal lymphocytes with polylobated nuclei in their peripheral blood, and provided that less than 5% of such cells remained, peripheral blood involvement was confirmed if more than 5% of these abnormal lymphocytes were present in the peripheral blood.25 The definition of extranodal lesions has been described previously.24 Lymph nodes and extranodal tumor lesions were both determined according to the Ann Arbor classification.2
We collected information regarding patient characteristics and underlying diseases (including a prognostic index for acute- and lymphoma-type ATL (ATL-PI)28). Factors used in analyses were listed in Table 1. The intensity of the conditioning regimen was classified as myeloablative and reduced intensity.29 An evaluation of the involved sites was based on the Shimoyama classification.2
Descriptive statistics were used to summarize variables related to patient demographic and transplant characteristics. Comparisons between the allo-SCT and CHT groups were performed using Fisher’s exact test, where appropriate, for categorical variables and the Mann–Whitney U-test for continuous variables. The Kaplan–Meier method was used to estimate OS after relapse. The log-rank test was used in the univariate analysis in order to compare OS. The impact of potential confounding factors on the appearance of involvement sites at relapse was evaluated using Fisher’s exact test and logistic regression analysis.
Leukocytosis was defined as a WBC count of 8.9 × 109/L or greater, with the median value as the cutoff level. Lactate dehydrogenase or blood urea nitrogen concentrations were dichotomized into normal and elevated concentrations.30 Serum albumin (ALB) was dichotomized into concentrations of 40.0 g/L (4.0 g/dL) or greater and less than 40.0 g/L (4.0 g/dL).2 Factors with at least borderline significance (P<0.25) according to the univariate analysis were included in the multivariate analysis. All analyses were performed using the SAS version 9.2 software (SAS Institute, Cary, NC, USA). Values of P<0.05 were considered significant in all analyses.
Patient characteristics and transplant procedures
Table 1 shows the patient characteristics of each group; 30 and 49 ATL patients relapsed after allo-SCT and CHT, respectively. In a total of 79 patients, the median intervals from CR to relapse and from the last treatment to relapse were 180 days (range, 28–3490) and 79 days (range, 9–3073), respectively. Intrathecal prophylaxis was not performed in 11 patients: 10 patients started the initial treatment before 2007 and 1 patient did not receive prophylaxis because of advanced age. Transplant procedures were shown in Table 2. In the allo-SCT group, nine patients achieved CR at the time of receiving allo-SCT, whereas 21 patients did not. One patient received a reduced-intensity conditioning regimen with antithymocyte globulin. No patients underwent in vitro T cell-depleted transplantation.
Comparison of involved sites at relapse between allo-SCT and CHT groups
The involvement sites at the initial diagnosis and relapse were shown in Table 3. At relapse, the frequency by which abnormal lymphocytes (⩾5%) developed in the peripheral blood was significantly lower in the allo-SCT group than in the CHT group (P<0.001). This was maintained when the percentage of abnormal lymphocytes as the threshold of peripheral blood involvement was considered to be ⩾2% or ⩾10% (data not shown). A multivariate analysis showed that the likelihood of developing abnormal lymphocytes in the peripheral blood at relapse was significantly lower in the allo-SCT group than in the CHT group (P<0.001; Table 4). We performed a stratification analysis according to the Shimoyama classification. In patients with the acute plus unfavorable chronic type, the frequency by which the allo-SCT group developed abnormal lymphocytes in peripheral blood at relapse was lower (P=0.001 by the multivariate analysis). However, this was not clear because of the small number of patients with the lymphoma type; relapse in the peripheral blood was observed in one and three patients in the allo-SCT (n=4) and CHT (n=7) groups, respectively (data not shown).
Relationship between primary and relapsed lesions
We next evaluated the relationship between initially diagnosed and relapsed lesions. The most frequent lesion of relapse was the primary lesion (that is, the lesion at the initial diagnosis); 19 (63.3%) and 43 (87.8%) patients in the allo-SCT and CHT groups had primary lesions (Figure 2). Among primary involved lesions, relapse significantly occurred at the same sites: lymph nodes (P=0.018), spleen (P=0.010) and gastrointestinal tract (P=0.005; see Supplementary Table S1). Relapse was only observed in new lesions in 11 (36.7%) and 6 (12.2%) patients in the allo-SCT and CHT groups, respectively. Lesions were more frequently observed in the CNS of patients who relapsed with new lesions only (P=0.005). The relapse pattern of patients in whom new lesions only occurred at relapse was more frequently observed in the allo-SCT group than in the CHT group (P=0.022). The multivariate analysis showed that the likelihood of relapse only in a new lesion was significantly higher in the allo-SCT group (P=0.014; Table 5), and was also the case when patients with the acute plus unfavorable chronic type were analyzed (P=0.048). We did not observe a similar result in patients with lymphoma type ATL because the number of patients was small.
We assessed the risk factors associated with CNS lesions at relapse, which was significantly observed as relapse only in a new lesion. The univariate analysis revealed that the frequency of CNS lesions at relapse was higher when ascites was detected at the initial diagnosis (P=0.006), with a short CR duration (P=0.037), and with a high sIL-2R value (P=0.024). In the multivariate analysis, the presence of ascites at the initial diagnosis and a short CR duration were also significant (P=0.016 and P=0.031, respectively), whereas a high sIL-2R value was not (P=0.051; see Supplementary Table S2).
Survival by the relapse pattern of ATL
The median survival times after relapse were 176 and 174 days in the allo-SCT and CHT groups, respectively (Figure 3). Estimated OS rates after relapse were 16.7% (95% confidence interval: 6.1–31.8%) and 3.0% (95% confidence interval: 0.2–12.9%) at 3 years in the allo-SCT and CHT groups, respectively. No significant differences were observed in the OS rates between the allo-SCT and CHT groups (P=0.198). The OS rates were poor for patients who relapsed in pleural effusion (P<0.001), ascites (P=0.005) and spleen (P=0.002), but was better for those who relapsed in the skin (P=0.031). The OS rates of the allo-SCT and CHT groups based on the involvement sites at relapse were shown in Supplementary Tables S3 and S4.
Relationship between GVHD and the involvement site
The timing of the relapse of ATL and GVHD was shown in Supplementary Table S5. In the allo-SCT group, 11 and 13 patients relapsed after the improvement of GVHD, and without any episode of GVHD, respectively. Of the 24 patients who had no clinical symptoms of GVHD at relapse, the most frequent lesions of relapse were detected in the skin (n=8) and lymph nodes (n=10).
Relationship between transplant procedures and the involvement site
We evaluated the impact of conditioning regimens for the involved lesion. The univariate analysis revealed that the intensity of the conditioning regimen was not associated with any involved lesion at relapse, including the TBI 12 Gy-based regimen, or the donor type (HLA-matched sibling vs alternative donor). The development of abnormal lymphocytes in the peripheral blood correlated with the use of an unrelated donor (P=0.037); of the four patients who relapsed in the peripheral blood, three and one patients underwent transplantation from unrelated BM and unrelated cord blood, respectively.
We here observed significant differences in the lesions involved in relapse after allo-SCT and CHT. To the best of our knowledge, this is the first study to evaluate the clinical features of ATL at the first relapse. It should be noted that the clinical features at relapse in the allo-SCT group were slightly more complex than those in the CHT group.
Leukemic relapse was less frequent in the allo-SCT group. Previous studies suggested that differences in extramedullary and BM relapse were attributed to the preferential occurrence of the GVL effect after transplantation for AML with stronger GVL effects in the blood system (that is, BM and peripheral blood) over extramedullary sites.31, 32, 33, 34 Although the underlying mechanism has not yet been elucidated in detail, an uneven graft-versus-ATL effect may explain, at least partly, the lower frequency of leukemic relapse following allo-SCT than CHT.
As we previously reported, chromosomal abnormalities and the overexpression of c-Met in ATL cells correlated with the type of involved sites at the initial diagnosis.35, 36 Considering the chromosomal instability of ATL,37 it would be of interest to clarify the intrinsic characteristics of ATL cells that affect the pathogenesis of the involved sites at relapse.
Skin lesions are generally observed in 25.0–48.9% of ATL patients at the initial diagnosis,2, 38 which is consistent with the results obtained in the present study at the initial diagnosis. In the allo-SCT group, relapse with skin involvement was more likely to develop in the absence of GVHD. We previously reported that recurrent ATL with skin involvement represented a good target for DLI;22 therefore, skin involvement needs to be accurately diagnosed. Although it is often difficult to distinguish a cutaneous lesion of ATL from other causes (including GVHD and viral infection),38 southern blotting analysis or high-throughput DNA sequencing may be a promising tool for an accurate diagnosis by showing the clonal proliferation of HTLV-1-infected cells.39, 40
An early and accurate diagnosis of relapse could be beneficial for selecting an appropriate treatment strategy (for example, DLI, radiation, intrathecal administration of CHT and mogamulizumab) and improving the prognosis of patients.17, 21, 22, 41 However, no standardized method has yet been established to detect the relapse of ATL after allo-SCT. In present clinical practices, symptoms are carefully monitored for the early detection of ATL relapse. Therefore, recognizing differences in relapse patterns between SCT and CHT, as well as in the sites of relapse likely to involve the primary lesion (that is, lymph nodes, spleen and gastrointestinal tract) and CNS as relapse only with new lesions, will be important. Diagnostic modalities for CNS involvement, such as lumbar puncture and diagnostic imaging, should be considered as soon as possible when neurological symptoms are noted in ATL patients, especially those with high-risk factors.
The present study highlighted the clinical features of relapsed ATL in a retrospective cohort. However, the present study had several limitations. The number of patients in our study was relatively small and patient characteristics were highly heterogeneous. Moreover, selection bias was unavoidable in patients who underwent allo-SCT. Therefore, these factors may have affected the results obtained; therefore, the results presented here should be interpreted carefully and need to be confirmed in a larger study.
In conclusion, we here demonstrated a lower rate of relapse in the peripheral blood and a higher rate of recurrent disease in new lesions only in post-transplant patients than in those receiving CHT. The optimal salvage treatment may be more effective, even for post-transplant patients, when the relapse of ATL is detected early and accurately; therefore, further clinical and experimental studies are needed to establish monitoring systems for patients with ATL.
Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H . Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood 1977; 50: 481–492.
Shimoyama M . Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma: a report from the Lymphoma Study Group (1984-87). Br J Haematol 1991; 79: 428–437.
Yamada Y, Tomonaga M, Fukuda H, Hanada S, Utsunomiya A, Tara M et al. A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study 9303. Br J Haematol 2001; 113: 375–382.
Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y et al. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG 9801. J Clin Oncol 2007; 25: 5458–5464.
Utsunomiya A, Miyazaki Y, Takatsuka Y, Hanada S, Uozumi K, Yashiki S et al. Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 27: 15–20.
Fukushima T, Miyazaki Y, Honda S, Kawano F, Moriuchi Y, Masuda M et al. Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma. Leukemia 2005; 19: 829–834.
Okamura J, Utsunomiya A, Tanosaki R, Uike N, Sonoda S, Kannagi M et al. Allogeneic stem-cell transplantation with reduced intensity as novel immunotherapy and antiviral therapy for adult T-cell leukemia/lymphoma. Blood 2005; 105: 4143–4145.
Kato K, Kanda Y, Eto T, Muta T, Gondo H, Taniguchi S et al. Allogeneic bone marrow transplantation from unrelated human T-cell leukemia virus-1-negative donors for adult T-cell leukemia/lymphoma: retrospective analysis of data from the Japan Marrow Donor Program. Biol Blood Marrow Transplant 2007; 13: 90–99.
Hishizawa M, Kanda J, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y et al. Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study. Blood 2010; 116: 1369–1376.
Ishida T, Hishizawa M, Kato K, Tanosaki R, Fukuda T, Taniguchi S et al. Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study. Blood 2012; 120: 1734–1741.
Fukushima T, Itonaga H, Moriuchi Y, Yoshida S, Taguchi J, Imaizumi Y et al. Feasibility of cord blood transplantation in chemosensitive adult T-cell leukemia/lymphoma: a retrospective analysis of the Nagasaki Transplantation Network. Int J Hematol 2013; 97: 485–490.
Yonekura K, Utsunomiya A, Takatsuka Y, Takeuchi S, Tashiro Y, Kanzaki T et al. Graft-versus-adult T-cell leukemia/lymphoma effect following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2008; 41: 1029–1035.
Shiratori S, Yasumoto A, Tanaka J, Shigematsu A, Yamamoto S, Nishio M et al. A retrospective analysis of allogeneic hematopoietic stem cell transplantation for adult T cell leukemia/lymphoma (ATL): clinical impact of graft-versus-leukemia/lymphoma effect. Biol Blood Marrow Transplant 2008; 14: 817–823.
Choi I, Tanosaki R, Uike N, Utsunomiya A, Tomonaga M, Harada M et al. Long-term outcomes after hematopoietic SCT for adult T-cell leukemia/lymphoma: results of prospective trials. Bone Marrow Transplant 2011; 46: 116–118.
Kanda J, Hishizawa M, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y et al. Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study. Blood 2012; 119: 2141–2148.
Tanosaki R, Uike N, Utsunomiya A, Saburi Y, Masuda M, Tomonaga M et al. Allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning for adult T-cell leukemia/lymphoma: impact of antithymoglobulin on clinical outcome. Biol Blood Marrow Transplant 2008; 14: 702–708.
Kamimura T, Miyamoto T, Kawano N, Numata A, Ito Y, Chong Y et al. Successful treatment by donor lymphocyte infusion of adult T-cell leukemia/lymphoma relapse following allogeneic hematopoietic stem cell transplantation. Int J Hematol 2012; 95: 725–730.
Fukushima T, Taguchi J, Moriuchi Y, Yoshida S, Itonaga H, Ando K et al. Allogeneic hematopoietic stem cell transplantation for ATL with central nervous system involvement: the Nagasaki transplant group experience. Int J Hematol 2011; 94: 390–394.
Itonaga H, Taguchi J, Fukushima T, Tsushima H, Sato S, Ando K et al. Distinct clinical features of infectious complications in adult T cell leukemia/lymphoma patients after allogeneic hematopoietic stem cell transplantation: a retrospective analysis in the Nagasaki transplant group. Biol Blood Marrow Transplant 2013; 19: 607–615.
Shigematsu A, Kobayashi N, Yasui H, Shindo M, Kakinoki Y, Koda K et al. High level of serum soluble interleukin-2 receptor at transplantation predicts poor outcome of allogeneic stem cell transplantation for adult T cell leukemia. Biol Blood Marrow Transplant 2014; 20: 801–805.
Simone CB 2nd, Morris JC, Stewart DM, Urquhart NE, Janik JE, Kreitman RJ et al. Radiation therapy for the management of patients with HTLV-1-associated adult T-cell leukemia/lymphoma. Blood 2012; 120: 1816–1819.
Itonaga H, Tsushima H, Taguchi J, Fukushima T, Taniguchi H, Sato S et al. Treatment of relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: the Nagasaki Transplant Group experience. Blood 2013; 121: 219–225.
Yamada Y . Phenotypic and functional analysis of leukemic cells from 16 patients with adult T-cell leukemia/lymphoma. Blood 1983; 61: 192–199.
Takasaki Y, Iwanaga M, Imaizumi Y, Tawara M, Joh T, Kohno T et al. Long-term study of indolent adult T-cell leukemia-lymphoma. Blood 2010; 115: 4337–4343.
Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr et al. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol 2009; 27: 453–459.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 2005; 11: 945–956.
Katsuya H, Yamanaka T, Ishitsuka K, Utsunomiya A, Sasaki H, Hanada S et al. Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma. J Clin Oncol 2012; 30: 1635–1640.
Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant 2009; 15: 367–369.
Major prognostic factors of patients with adult T-cell leukemia-lymphoma: a cooperative study. Lymphoma Study Group (1984-1987). Leuk Res 1991; 15: 81–90.
Yoshihara S, Ikegame K, Kaida K, Taniguchi K, Kato R, Inoue T et al. Incidence of extramedullary relapse after haploidentical SCT for advanced AML/myelodysplastic syndrome. Bone Marrow Transplant 2012; 47: 669–676.
Potenza L, Luppi M, Riva G, Morselli M, Ferrari A, Imovilli A et al. Isolated extramedullary relapse after autologous bone marrow transplantation for acute myeloid leukemia: case report and review of the literature. Am J Hematol 2006; 81: 45–50.
Choi SJ, Lee JH, Lee JH, Kim S, Seol M, Lee YS et al. Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse. Leukemia 2004; 18: 1789–1797.
Yoshihara S, Ando T, Ogawa H . Extramedullary relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation: an easily overlooked but significant pattern of relapse. Biol Blood Marrow Transplant 2012; 18: 1800–1807.
Itoyama T, Chaganti RS, Yamada Y, Tsukasaki K, Atogami S, Nakamura H et al. Cytogenetic analysis of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki. Blood 2001; 97: 3612–3620.
Imaizumi Y, Murota H, Kanda S, Hishikawa Y, Koji T, Taguchi T et al. Expression of the c-Met proto-oncogene and its possible involvement in liver invasion in adult T-cell leukemia. Clin Cancer Res 2003; 9: 181–187.
Tsukasaki K, Krebs J, Nagai K, Tomonaga M, Koeffler HP, Bartram CR et al. Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course. Blood 2001; 97: 3875–3881.
Yamaguchi T, Ohshima K, Karube K, Tutiya T, Kawano R, Suefuji H et al. Clinicopathological features of cutaneous lesions of adult T-cell leukemia/lymphoma. Br J Dermatol 2005; 152: 76–81.
Cook LB, Melamed A, Niederer H, Valganon M, Laydon D, Foroni L et al. The role of HTLV-1 clonality, proviral structure, and genomic integration site in adult T-cell leukemia/lymphoma. Blood 2014; 123: 3925–3931.
Firouzi S, López Y, Suzuki Y, Nakai K, Sugano S, Yamochi T et al. Development and validation of a new high-throughput method to investigate the clonality of HTLV-1-infected cells based on provirus integration sites. Genome Med 2014; 6: 46.
Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol 2012; 30: 837–842.
We thank the hematologists at the Department of Hematology, Atomic Bomb Disease and Hibakusya Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, for the diagnosis and treatment of patients with ATL. This study was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare of Japan and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
HI, JT and Y Miyazaki conceived and designed the study; HI, H Taniguchi, JM and Y Miyazaki collected the data; HI and Y Miyazaki analyzed the data; HI, SH and Y Miyazaki performed the statistical analyses; HI and Y Miyazaki wrote the manuscript and created the figures and tables; and all authors critically reviewed the manuscript and read and approved the final version.
The authors declare no conflict of interest.
Supplementary Information accompanies this paper on Bone Marrow Transplantation website
About this article
Clinical Features and Treatment Outcomes of Hematopoietic Stem Cell Transplantation During 2006-2016 at a Single Institution in Miyazaki Prefecture
Journal of Hematopoietic Cell Transplantation (2019)
Cord Blood Transplantation Provided Long-term Remission in a Case of Adult T-cell Leukemia-lymphoma (ATL) with Myelofibrosis
Internal Medicine (2016)