Adult T-cell leukemia-lymphoma
Section editor | |
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Bhagirathbhai Dholaria, MBBS Vanderbilt University Nashville, TN |
5 regimens on this page
5 variants on this page
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Guidelines
NCCN
Untreated
CHOP-14
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CHOP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne every 14 days
CHOP-DI: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Dose-Intense
I-CHOP: Intensive Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
Regimen
Study | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
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Itoh et al. 2002 (JCOG 9505) | Randomized Phase II (E) | dose-escalated CHOP | Seems not superior | Less toxic |
Tsukasaki et al. 2007 (JCOG 9801) | Phase III (C) | mLSG15 | Seems to have inferior CR rate | Less toxic |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Filgrastim (Neupogen) given once ANC decreased to less than 1000/uL and continued once per day until count increased to greater than 5000/uL
14-day cycle for 8 cycles
Intrathecal component
Intrathecal triple-therapy was given during recovery phase of cycles 1, 3, and 5 after platelet count was greater than 70 × 109/L.
- Cytarabine (Ara-C) 40 mg IT
- Methotrexate (MTX) 15 mg IT
- Prednisone (Sterapred) 10 mg IT
3 doses, total
References
- JCOG 9505: Itoh K, Ohtsu T, Fukuda H, Sasaki Y, Ogura M, Morishima Y, Chou T, Aikawa K, Uike N, Mizorogi F, Ohno T, Ikeda S, Sai T, Taniwaki M, Kawano F, Niimi M, Hotta T, Shimoyama M, Tobinai K; Members of the lymphoma study group of the Japan Clinical Oncology Group (JCOG). Randomized phase II study of biweekly CHOP and dose-escalated CHOP with prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin's lymphoma: Japan Clinical Oncology Group Study 9505. Ann Oncol. 2002 Sep;13(9):1347-55. link to original article PubMed
- JCOG 9801: Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, Masuda M, Nagoshi H, Ueda R, Tamura K, Sano M, Momita S, Yamaguchi K, Kawano F, Hanada S, Tobinai K, Shimoyama M, Hotta T, Tomonaga M; Japan Clinical Oncology Group Study JCOG9801. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007 Dec 1;25(34):5458-64. Epub 2007 Oct 29. link to original article contains verified protocol PubMed
Interferon alfa-2b & Zidovudine
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Regimen
Study | Evidence |
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Gill et al. 1995 | Non-randomized, <20 pts |
Of historic interest.
Immunotherapy
References
- Gill PS, Harrington W Jr, Kaplan MH, Ribeiro RC, Bennett JM, Liebman HA, Bernstein-Singer M, Espina BM, Cabral L, Allen S, Kornblau S, Pike MC, Levine AM. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med. 1995 Jun 29;332(26):1744-8. link to original article PubMed
LSG15
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Regimen
Study | Evidence |
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Yamada et al. 2001 (JCOG 9303) | Phase II |
Ranimustine is not available in the United States and is approved only in Japan. This regimen was notable for excess CNS relapses and was subsequently replaced by mLSG15.
Chemotherapy
- Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Cyclophosphamide (Cytoxan) 350 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1, then 30 mg/m2 IV once on day 8
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1, 8, 15 to 17
- Ranimustine (Cymerin) 60 mg/m2 IV once on day 8
- Vindesine (Eldisine) 2.4 mg/m2 IV once on day 15
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 15 to 17
- Carboplatin (Paraplatin) 250 mg/m2 IV once on day 15
28-day cycle for 7 cycles
References
- Yamada Y, Tomonaga M, Fukuda H, Hanada S, Utsunomiya A, Tara M, Sano M, Ikeda S, Takatsuki K, Kozuru M, Araki K, Kawano F, Niimi M, Tobinai K, Hotta T, Shimoyama M. A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303. Br J Haematol. 2001 May;113(2):375-82. link to original article PubMed
mLSG15
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Tsukasaki et al. 2007 (JCOG 9801) | Phase III (E) | CHOP-14 | Seems to have superior CR rate |
Ishida et al. 2015 | Randomized Phase II (C) | mLSG15 & Mogamulizumab | Seems not superior |
Ranimustine is not available in the United States and is approved only in Japan.
Chemotherapy
- Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Cyclophosphamide (Cytoxan) 350 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1, then 30 mg/m2 IV once on day 8
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1, 8, 15 to 17
- Ranimustine (Cymerin) 60 mg/m2 IV once on day 8
- Vindesine (Eldisine) 2.4 mg/m2 IV once on day 15
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 15 to 17
- Carboplatin (Paraplatin) 250 mg/m2 IV once on day 15
28-day cycle for 6 cycles
CNS prophylaxis
- Cytarabine (Ara-C) 40 mg IT, admixed with MTX & prednisone
- Methotrexate (MTX) 15 mg IT, admixed with Ara-C & prednisone
- Prednisone (Sterapred) 10 mg IT, admixed with Ara-C & MTX
Given after cycles 1, 3, and 5 after platelets greater than 70 × 109/L and within 2 days before the next cycle
References
- Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, Masuda M, Nagoshi H, Ueda R, Tamura K, Sano M, Momita S, Yamaguchi K, Kawano F, Hanada S, Tobinai K, Shimoyama M, Hotta T, Tomonaga M; Japan Clinical Oncology Group Study JCOG9801. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007 Dec 1;25(34):5458-64. Epub 2007 Oct 29. link to original article contains verified protocol PubMed
- Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015 Jun;169(5):672-82. Epub 2015 Mar 2. link to original article link to PMC article PubMed
Relapsed or refractory
Alemtuzumab monotherapy
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Regimen
Study | Evidence |
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Sharma P et al. 2016 | Phase II |
Chemotherapy
- Alemtuzumab (Campath) 30 mg IV once per day on days 1, 3, 5 (three times per week)
7-day cycle for up to 7 cycles
References
- Sharma K, Janik JE, O'Mahony D, Stewart D, Pittaluga S, Stetler-Stevenson M, Jaffe ES, Raffeld M, Fleisher TA, Lee CC, Steinberg SM, Waldmann TA, Morris JC. Phase II study of alemtuzumab (CAMPATH-1) in patients with HTLV-1-associated adult T-cell leukemia/lymphoma. Clin Cancer Res. 2017 Jan 1;23(1):35-42. Epub 2016 Aug 2. link to original article contain protocol link to PMC article PubMed
Lenalidomide monotherapy
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Regimen
Study | Evidence | ORR |
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Ishida et al. 2016 (ATLL-002) | Phase II | 42% (95% CI 23-63) |
Chemotherapy
- Lenalidomide (Revlimid) 25 mg PO once per day
Continued indefinitely
References
- ATLL-002: Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. J Clin Oncol. 2016 Dec;34(34):4086-4093. link to original article PubMed