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Lenalidomide in patients with Relapsed or Refractory HTLV-1 Related Adult T cell Leukemia/Lymphoma (ATLL)

Lenalidomide in patients with Relapsed or Refractory HTLV-1 Related Adult T cell... efficacy in several hematologic malignancies. Hypothesized Adult T-cell Leukemia/Lymphoma (ATLL) is resistant to mechanisms of action include immunomodulatory effects, direct chemotherapy and the acute and lymphomatous subtypes of cytotoxicity to tumor cells, enhanced natural killer and T-cell disease have a dismal prognosis. There is no standard therapy function and anti-angiogenic activity [3]. Lenalidomide is approved for relapsed or refractory disease in Western countries and new agents are being explored. Lenalidomide is an immunomodulatory for myelodysplastic syndrome and multiple myeloma and has shown agent with promising activity in hematologic malignancies, promising efficacy in chronic lymphocytic leukemia, non-Hogdkin’s including non-Hodgkin’s lymphoma and represents a novel lymphoma and cutaneous T cell lymphoma [4]. A phase 2 study therapeutic option. We investigated the safety and efficacy of of lenalidomide in ATLL is ongoing in Japan [5]. We conducted a lenalidomide (25 mg once daily) on Days 1 to 21 of every 28-day prospective study of lenalidomide in North American patients with cycle in a phase two study of patients with relapsed or refractory ATLL. The study was closed early due to limited patient accrual. relapsed or refractory ATLL. The study was closed early due to Of 4 patients enrolled, no response was observed in two patients limited patient accrual, however we report the experience of the four evaluable for response. No grade 3 or 4 toxicity was noted. In this enrolled patients. small single institution experience, lenalidomide showed no clinical activity and manageable toxicity in two evaluable patients with For this phase II study, key inclusion criteria were age ≥ 18years, relapsed or refractory ATLL. This experience highlights the need a confirmed diagnosis of relapsed or refractory ATLL of the acute for collaborative studies of this rare disease and enrolling patients or lymphomatous subtype, Eastern Cooperative Oncology Group on clinical trials promptly. (ECOG) performance status of ≤ 2, and acceptable laboratory Keywords parameters. Women of childbearing potential required a negative HTLV-1, ATLL, Non-Hodgkin’s Lymphoma, Therapy serum or urine pregnancy test and agreed to commit to abstinence from heterosexual intercourse or to begin two acceptable methods of birth control. Men agreed not to father a child and to use a Case Presentation condom with partners of child-bearing potential even after successful Adult T-Cell Leukemia/Lymphoma (ATLL) is a rare and vasectomy. Key exclusion criteria were any serious medical aggressive peripheral T-cell neoplasm caused by the Human T-cell condition, laboratory abnormality, or psychiatric illness that would Lymphotropic Virus Type-I (HTLV-I), a type C human retrovirus prevent signing the informed consent form, known hypersensitivity endemic in parts of Japan, sub-Saharan Africa, the Caribbean basin, to thalidomide, known positivity for HIV or infectious hepatitis, type as well as the United States where immigrants of endemic countries B or C and recent deep venous thrombosis/pulmonary embolism reside. Patients with the acute and lymphomatous subtypes of ATLL requiring dose adjustments of anticoagulation within two months. have a poor prognosis with a median survival of only 6 to 13 months The study was designed in accordance with the general ethical despite aggressive chemotherapy [1,2]. There is no standard of care principles outlined in the Declaration of Helsinki and was approved for relapsed or refractory disease in Western countries; however by the Institutional Review Board of Columbia University. novel therapies are under investigation. Citation: Phillips AA, Giddings J, Lee SM, Horwitz SM (2015) Lenalidomide in patients with Relapsed or Refractory HTLV-1 Related Adult T cell Leukemia/Lymphoma (ATLL). Int J Blood Res Disord 2:010 Received: February 13, 2015: Accepted: March 18, 2015: Published: March 21, 2015 ClinMed Copyright: © 2015 Phillips AA. This is an open-access article distributed under the International Library terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Table 1: Patient characteristics The optimal therapeutic strategy for relapsed ATLL is unknown, primarily because it has been challenging to conduct prospective, Characteristics N=4 Median age (range), years 54 (36-56) randomized and multi-institutional trials. A low overall incidence Sex M/F 1:3 and prevalence of ATLL combined with the aggressive nature of Ethnic origin All Caribbean the disease, difficulty with response assessments because of complex Clinical subtype of ATLL Acute 3 presentations with leukemic, lymphomatous and skin compartments, Lymphoma 1 and the immunocompromised nature of patients who frequently Median ECOG performance status (range) 1 (0-2) have multi-organ system dysfunction preventing cytotoxic therapy, Median number of prior therapies (range) 4 (2-9) all contribute to the challenge. The largest study of relapsed ATLL Response 0/4 enrolled 28 patients in multiple centers in Japan and led to the approval of mogamuluzimab in Japan based on an overall response Eligible patients received oral lenalidomide (25 mg once daily) rate of 50%, and median progression-free survival and overall survival on Days 1 to 21 of every 28-day cycle. Treatment was continued of 5.2 and 13.7 months, respectively [11].The most common adverse until evidence of progressive disease, intolerable side effects, patient events included infusion reactions (89%) and skin rash (63%). choice to withdraw, or death. The primary endpoint was overall Mogamulizumab is an investigational agent in the U.S. and has not response rate (ORR) as defined by the Japanese Clinical Oncology been approved for any indication by the FDA however current trials Group (JCOG) response criteria for ATLL [6]. Secondary endpoints in ATLL, cutaneous T cell lymphoma, and non-Hodgkin’s lymphoma were tumor control rate, duration of response, time to progression, are ongoing. progression-free survival, and safety. Outside of Japan, the AIDS Malignancy Consortium treated 19 The characteristics of the four patients who consented for the patients with aggressive ATLL (N=19) with EPOCH chemotherapy study between February 2011 and June 2013 are presented in Table followed by antiviral therapy and interferon for up to one year 1. There were 3 women and 1 man with a median age at diagnosis resulting in an ORR of 58% (CR 10.5%) and a median duration of of 54 years (range 36 to 56). All had emigrated from the Caribbean, response of 13 months. Although this regimen appeared active, viral three had the acute subtype of disease, one had the lymphomatous replication during therapy coincided with disease progression, which subtype of disease, and the median ECOG performance status was likely contributed to treatment failure [12]. A number of small studies 1 (range 0-2). The median number of prior therapies was 4 (range and cases have reported the activity of combination zidovudine and 2 to 9).Of the 4 patients enrolled, one progressed before receiving IFN-alpha and demonstrated a high response rate in previously therapy and the remaining three patients received lenalidomide untreated and treatment refractory patients. A retrospective meta- for one day, 15 days and 21 days respectively. In the two patients analysis suggests this therapy is most effective for all subtypes evaluable for response after a 28 day cycle, no therapeutic response but lymphoma [13]. A randomized trial has not been conducted. was observed. In addition, no grade 3 or 4 toxicity was observed, with Novel agents for the potential application to the treatment of ATLL the most common toxicities being grade 1 fatigue (3/4), and grade 1 include pralatrexate, bortezomib, forodesine, and histone deacteylase thrombocytopenia (2/4). All patients ultimately expired of relapsed inhibitors [5]. disease, with overall survival ranging from 7 to 62 months. The trial was closed early due to limited patient accrual. Clinical trial participation continues to be a desirable option and multi-center collaborative efforts should evaluate patients promptly In this small single institution experience, lenalidomide showed before deterioration of performance status, opportunistic infection no clinical activity and manageable toxicity in two evaluable patients and multi-system organ dysfunction set in. This phase II study was with relapsed or refractory ATLL. Two additional patients progressed closed prematurely but showed no clinical activity in two patients shortly after enrolling in the study. It is challenging to interpret evaluable for response. the lack of clinical activity observed as this was a highly refractory, heavily pretreated patient population and only two patients were References evaluable for response; however, this experience highlights the need 1. Shimoyama M (1991) Diagnostic criteria and classification of clinical subtypes for collaborative studies of this rare disease and enrolling patients on of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol 79: 428-437. clinical trials promptly. 2. Taguchi H, Kinoshita KI, Takatsuki K, Tomonaga M, Araki K, et al. (1996) An Lenalidomide was selected for this study because preclinical and intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed early clinical studies suggest that lenalidomide has anti-tumor activity by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support. J Acquir Immune Defic Syndr Hum against relapsed or refractory T-cell lymphomas, including ATLL, Retrovirol 12: 182–86. even though its mechanism is not well understood. ATLL derived 3. Bartlett JB, Dredge K, Dalgleish AG (2004) The evolution of thalidomide and cells secrete high levels of vascular endothelial growth factor (VEGF) its IMiD derivatives as anticancer agents. Nat Rev Cancer 4: 314-322. and basic fibroblast growth factor (b-FGF), induce endothelial tube 4. Wiernik PH (2013) Lenalidomide in lymphomas and chronic lymphocytic formation in vitro and establish functional gap junction-mediated leukemia. Expert Opin Pharmacother 14: 475-488. communication with endothelial cells suggesting a potential role 5. Tobinai K (2010) Clinical trials for human T-cell lymphotropic virus type for anti-angiogenesis [7]. Lenalidomide enhanced the cytotoxicity I-associated peripheral T-cell lymphoma in Japan. Semin Hematol 47 Suppl of HTLV-I positive cells without a direct anti-proliferative effect on 1: S5-7. those cell lines, an effect possibly mediated through CD56 positive 6. Yamada Y, Tomonaga M, Fukuda H, Hanada S, Utsunomiya A, et al. (2001) cells stimulated by lenalidomide [8]. The antimyeloma activity of A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303. Br J lenalidomide and pomalidomide has recently been attributed to Haematol 113: 375-382. Cerebron (CRBN), although further studies are necessary to elucidate 7. Kchour G, Tarhini M, Sharifi N, Farid R, Khooei AR, et al. (2008) Increased the role it may have in other hematologic malignancies, including microvessel density in involved organs from patients with HTLV-I associated ATLL [9]. A tumor flare reaction following lenalidomide has been adult T cell leukemia lymphoma. Leuk Lymphoma 49: 265-270. described in a number of hematologic malignancies and can easily 8. Kitagawa Y, Matsuoka M, Mitani S (2001) Effect of lenalidomide on antileukemia be mistaken for disease progression. The pathophysiology of tumor activity in vitro against adult T-cell leukemia (ATL). J Clin Oncol 29: 2001. flare is unclear although it is likely some form of immunomodulatory 9. Zhu YX, Braggio E, Shi CX, Bruins LA, Schmidt JE, et al. (2011) Cereblon mechanism [10]. Future studies of ATLL patients on lenalidomide expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood 118: 4771-4779. therapy for longer durations should take this into consideration. Phillips et al. Int J Blood Res Disord 2015, 2:1 • Page 2 of 3 • ISSN: 2469-5696 10. Chanan-Khan AA, Chitta K, Ersing N, Paulus A, Masood A, et al. (2011) 12. Ratner L, Harrington W, Feng X, Grant C, Jacobson S, et al. (2009) Human Biological effects and clinical significance of lenalidomide-induced tumour T cell leukemia virus reactivation with progression of adult T-cell leukemia- flare reaction in patients with chronic lymphocytic leukaemia: in vivo evidence lymphoma. PLoS One 4: e4420. of immune activation and antitumour response. Br J Haematol 155: 457-467. 13. Bazarbachi A, Plumelle Y, Carlos Ramos J, Tortevoye P, Otrock Z, et al. 11. Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, et al. (2012) (2010) Meta-analysis on the use of zidovudine and interferon-alfa in adult Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia/lymphoma showing improved survival in the leukemic T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol 30: 837- subtypes. J Clin Oncol 28: 4177-4183. Phillips et al. Int J Blood Res Disord 2015, 2:1 • Page 3 of 3 • ISSN: 2469-5696 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Blood Research and Disorders Unpaywall

Lenalidomide in patients with Relapsed or Refractory HTLV-1 Related Adult T cell Leukemia/Lymphoma (ATLL)

International Journal of Blood Research and DisordersJun 30, 2015

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2469-5696
DOI
10.23937/2469-5696/1410010
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Abstract

efficacy in several hematologic malignancies. Hypothesized Adult T-cell Leukemia/Lymphoma (ATLL) is resistant to mechanisms of action include immunomodulatory effects, direct chemotherapy and the acute and lymphomatous subtypes of cytotoxicity to tumor cells, enhanced natural killer and T-cell disease have a dismal prognosis. There is no standard therapy function and anti-angiogenic activity [3]. Lenalidomide is approved for relapsed or refractory disease in Western countries and new agents are being explored. Lenalidomide is an immunomodulatory for myelodysplastic syndrome and multiple myeloma and has shown agent with promising activity in hematologic malignancies, promising efficacy in chronic lymphocytic leukemia, non-Hogdkin’s including non-Hodgkin’s lymphoma and represents a novel lymphoma and cutaneous T cell lymphoma [4]. A phase 2 study therapeutic option. We investigated the safety and efficacy of of lenalidomide in ATLL is ongoing in Japan [5]. We conducted a lenalidomide (25 mg once daily) on Days 1 to 21 of every 28-day prospective study of lenalidomide in North American patients with cycle in a phase two study of patients with relapsed or refractory ATLL. The study was closed early due to limited patient accrual. relapsed or refractory ATLL. The study was closed early due to Of 4 patients enrolled, no response was observed in two patients limited patient accrual, however we report the experience of the four evaluable for response. No grade 3 or 4 toxicity was noted. In this enrolled patients. small single institution experience, lenalidomide showed no clinical activity and manageable toxicity in two evaluable patients with For this phase II study, key inclusion criteria were age ≥ 18years, relapsed or refractory ATLL. This experience highlights the need a confirmed diagnosis of relapsed or refractory ATLL of the acute for collaborative studies of this rare disease and enrolling patients or lymphomatous subtype, Eastern Cooperative Oncology Group on clinical trials promptly. (ECOG) performance status of ≤ 2, and acceptable laboratory Keywords parameters. Women of childbearing potential required a negative HTLV-1, ATLL, Non-Hodgkin’s Lymphoma, Therapy serum or urine pregnancy test and agreed to commit to abstinence from heterosexual intercourse or to begin two acceptable methods of birth control. Men agreed not to father a child and to use a Case Presentation condom with partners of child-bearing potential even after successful Adult T-Cell Leukemia/Lymphoma (ATLL) is a rare and vasectomy. Key exclusion criteria were any serious medical aggressive peripheral T-cell neoplasm caused by the Human T-cell condition, laboratory abnormality, or psychiatric illness that would Lymphotropic Virus Type-I (HTLV-I), a type C human retrovirus prevent signing the informed consent form, known hypersensitivity endemic in parts of Japan, sub-Saharan Africa, the Caribbean basin, to thalidomide, known positivity for HIV or infectious hepatitis, type as well as the United States where immigrants of endemic countries B or C and recent deep venous thrombosis/pulmonary embolism reside. Patients with the acute and lymphomatous subtypes of ATLL requiring dose adjustments of anticoagulation within two months. have a poor prognosis with a median survival of only 6 to 13 months The study was designed in accordance with the general ethical despite aggressive chemotherapy [1,2]. There is no standard of care principles outlined in the Declaration of Helsinki and was approved for relapsed or refractory disease in Western countries; however by the Institutional Review Board of Columbia University. novel therapies are under investigation. Citation: Phillips AA, Giddings J, Lee SM, Horwitz SM (2015) Lenalidomide in patients with Relapsed or Refractory HTLV-1 Related Adult T cell Leukemia/Lymphoma (ATLL). Int J Blood Res Disord 2:010 Received: February 13, 2015: Accepted: March 18, 2015: Published: March 21, 2015 ClinMed Copyright: © 2015 Phillips AA. This is an open-access article distributed under the International Library terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Table 1: Patient characteristics The optimal therapeutic strategy for relapsed ATLL is unknown, primarily because it has been challenging to conduct prospective, Characteristics N=4 Median age (range), years 54 (36-56) randomized and multi-institutional trials. A low overall incidence Sex M/F 1:3 and prevalence of ATLL combined with the aggressive nature of Ethnic origin All Caribbean the disease, difficulty with response assessments because of complex Clinical subtype of ATLL Acute 3 presentations with leukemic, lymphomatous and skin compartments, Lymphoma 1 and the immunocompromised nature of patients who frequently Median ECOG performance status (range) 1 (0-2) have multi-organ system dysfunction preventing cytotoxic therapy, Median number of prior therapies (range) 4 (2-9) all contribute to the challenge. The largest study of relapsed ATLL Response 0/4 enrolled 28 patients in multiple centers in Japan and led to the approval of mogamuluzimab in Japan based on an overall response Eligible patients received oral lenalidomide (25 mg once daily) rate of 50%, and median progression-free survival and overall survival on Days 1 to 21 of every 28-day cycle. Treatment was continued of 5.2 and 13.7 months, respectively [11].The most common adverse until evidence of progressive disease, intolerable side effects, patient events included infusion reactions (89%) and skin rash (63%). choice to withdraw, or death. The primary endpoint was overall Mogamulizumab is an investigational agent in the U.S. and has not response rate (ORR) as defined by the Japanese Clinical Oncology been approved for any indication by the FDA however current trials Group (JCOG) response criteria for ATLL [6]. Secondary endpoints in ATLL, cutaneous T cell lymphoma, and non-Hodgkin’s lymphoma were tumor control rate, duration of response, time to progression, are ongoing. progression-free survival, and safety. Outside of Japan, the AIDS Malignancy Consortium treated 19 The characteristics of the four patients who consented for the patients with aggressive ATLL (N=19) with EPOCH chemotherapy study between February 2011 and June 2013 are presented in Table followed by antiviral therapy and interferon for up to one year 1. There were 3 women and 1 man with a median age at diagnosis resulting in an ORR of 58% (CR 10.5%) and a median duration of of 54 years (range 36 to 56). All had emigrated from the Caribbean, response of 13 months. Although this regimen appeared active, viral three had the acute subtype of disease, one had the lymphomatous replication during therapy coincided with disease progression, which subtype of disease, and the median ECOG performance status was likely contributed to treatment failure [12]. A number of small studies 1 (range 0-2). The median number of prior therapies was 4 (range and cases have reported the activity of combination zidovudine and 2 to 9).Of the 4 patients enrolled, one progressed before receiving IFN-alpha and demonstrated a high response rate in previously therapy and the remaining three patients received lenalidomide untreated and treatment refractory patients. A retrospective meta- for one day, 15 days and 21 days respectively. In the two patients analysis suggests this therapy is most effective for all subtypes evaluable for response after a 28 day cycle, no therapeutic response but lymphoma [13]. A randomized trial has not been conducted. was observed. In addition, no grade 3 or 4 toxicity was observed, with Novel agents for the potential application to the treatment of ATLL the most common toxicities being grade 1 fatigue (3/4), and grade 1 include pralatrexate, bortezomib, forodesine, and histone deacteylase thrombocytopenia (2/4). All patients ultimately expired of relapsed inhibitors [5]. disease, with overall survival ranging from 7 to 62 months. The trial was closed early due to limited patient accrual. Clinical trial participation continues to be a desirable option and multi-center collaborative efforts should evaluate patients promptly In this small single institution experience, lenalidomide showed before deterioration of performance status, opportunistic infection no clinical activity and manageable toxicity in two evaluable patients and multi-system organ dysfunction set in. This phase II study was with relapsed or refractory ATLL. Two additional patients progressed closed prematurely but showed no clinical activity in two patients shortly after enrolling in the study. It is challenging to interpret evaluable for response. the lack of clinical activity observed as this was a highly refractory, heavily pretreated patient population and only two patients were References evaluable for response; however, this experience highlights the need 1. Shimoyama M (1991) Diagnostic criteria and classification of clinical subtypes for collaborative studies of this rare disease and enrolling patients on of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol 79: 428-437. clinical trials promptly. 2. Taguchi H, Kinoshita KI, Takatsuki K, Tomonaga M, Araki K, et al. (1996) An Lenalidomide was selected for this study because preclinical and intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed early clinical studies suggest that lenalidomide has anti-tumor activity by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support. J Acquir Immune Defic Syndr Hum against relapsed or refractory T-cell lymphomas, including ATLL, Retrovirol 12: 182–86. even though its mechanism is not well understood. ATLL derived 3. Bartlett JB, Dredge K, Dalgleish AG (2004) The evolution of thalidomide and cells secrete high levels of vascular endothelial growth factor (VEGF) its IMiD derivatives as anticancer agents. Nat Rev Cancer 4: 314-322. and basic fibroblast growth factor (b-FGF), induce endothelial tube 4. Wiernik PH (2013) Lenalidomide in lymphomas and chronic lymphocytic formation in vitro and establish functional gap junction-mediated leukemia. Expert Opin Pharmacother 14: 475-488. communication with endothelial cells suggesting a potential role 5. Tobinai K (2010) Clinical trials for human T-cell lymphotropic virus type for anti-angiogenesis [7]. Lenalidomide enhanced the cytotoxicity I-associated peripheral T-cell lymphoma in Japan. Semin Hematol 47 Suppl of HTLV-I positive cells without a direct anti-proliferative effect on 1: S5-7. those cell lines, an effect possibly mediated through CD56 positive 6. Yamada Y, Tomonaga M, Fukuda H, Hanada S, Utsunomiya A, et al. (2001) cells stimulated by lenalidomide [8]. The antimyeloma activity of A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303. Br J lenalidomide and pomalidomide has recently been attributed to Haematol 113: 375-382. Cerebron (CRBN), although further studies are necessary to elucidate 7. Kchour G, Tarhini M, Sharifi N, Farid R, Khooei AR, et al. (2008) Increased the role it may have in other hematologic malignancies, including microvessel density in involved organs from patients with HTLV-I associated ATLL [9]. A tumor flare reaction following lenalidomide has been adult T cell leukemia lymphoma. Leuk Lymphoma 49: 265-270. described in a number of hematologic malignancies and can easily 8. Kitagawa Y, Matsuoka M, Mitani S (2001) Effect of lenalidomide on antileukemia be mistaken for disease progression. The pathophysiology of tumor activity in vitro against adult T-cell leukemia (ATL). J Clin Oncol 29: 2001. flare is unclear although it is likely some form of immunomodulatory 9. Zhu YX, Braggio E, Shi CX, Bruins LA, Schmidt JE, et al. (2011) Cereblon mechanism [10]. Future studies of ATLL patients on lenalidomide expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood 118: 4771-4779. therapy for longer durations should take this into consideration. Phillips et al. Int J Blood Res Disord 2015, 2:1 • Page 2 of 3 • ISSN: 2469-5696 10. Chanan-Khan AA, Chitta K, Ersing N, Paulus A, Masood A, et al. (2011) 12. Ratner L, Harrington W, Feng X, Grant C, Jacobson S, et al. (2009) Human Biological effects and clinical significance of lenalidomide-induced tumour T cell leukemia virus reactivation with progression of adult T-cell leukemia- flare reaction in patients with chronic lymphocytic leukaemia: in vivo evidence lymphoma. PLoS One 4: e4420. of immune activation and antitumour response. Br J Haematol 155: 457-467. 13. Bazarbachi A, Plumelle Y, Carlos Ramos J, Tortevoye P, Otrock Z, et al. 11. Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, et al. (2012) (2010) Meta-analysis on the use of zidovudine and interferon-alfa in adult Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia/lymphoma showing improved survival in the leukemic T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol 30: 837- subtypes. J Clin Oncol 28: 4177-4183. Phillips et al. Int J Blood Res Disord 2015, 2:1 • Page 3 of 3 • ISSN: 2469-5696

Journal

International Journal of Blood Research and DisordersUnpaywall

Published: Jun 30, 2015

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