T-cell acute lymphoblastic leukemia

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Martin W. Schoen, MD, MPH
Saint Louis University
St. Louis, MO

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Bhagirathbhai Dholaria, MBBS
Vanderbilt University
Nashville, TN

Note that many of the regimens used to treat this disease are generic to B-cell acute lymphoblastic leukemia; this page contains regimens that are specific to T-cell acute lymphoblastic leukemia (a.k.a. T-cell lymphoblastic lymphoma when primarily nodal-based). Note: certain regimens have been moved to dedicated pages:

5 regimens on this page
6 variants on this page


Guidelines

"How I Treat"

NCCN

Pre-phase

Prednisone monotherapy

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Regimen

Study Evidence
Lepretre et al. 2015 (GRAALL-LYSA LL03) Phase II

Chemotherapy

CNS prophylaxis

7-day course

Subsequent treatment

References

  1. GRAALL-LYSA LL03: Lepretre S, Touzart A, Vermeulin T, Picquenot JM, Tanguy-Schmidt A, Salles G, Lamy T, Béné MC, Raffoux E, Huguet F, Chevallier P, Bologna S, Bouabdallah R, Benichou J, Brière J, Moreau A, Tallon-Simon V, Seris S, Graux C, Asnafi V, Ifrah N, Macintyre E, Dombret H. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study. J Clin Oncol. 2016 Feb 20;34(6):572-80. Epub 2015 Dec 7. link to original article link to data supplement contains protocol PubMed NCT00195871

Upfront induction therapy

Cyclophosphamide, Daunorubicin, L-Asparaginase, Vincristine, Prednisone

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Regimen, "Pediatric-like GRAALL reinforced induction"

Study Evidence
Lepretre et al. 2015 (GRAALL-LYSA LL03) Phase II

Note: This regimen was meant for patients less than 60 years old (up to age 59). Regimen is as per the GRAALL-2003 Study with some minor differences. High-risk patients with an HLA sibling-matched donor or a fully matched (10/10) unrelated donor who achieved CR1 were offered allogeneic stem cell transplant.

Preceding treatment

Chemotherapy

Supportive medications

CNS prophylaxis

28-day course

Subsequent treatment

  • See paper for details beyond induction

References

  1. GRAALL-LYSA LL03: Lepretre S, Touzart A, Vermeulin T, Picquenot JM, Tanguy-Schmidt A, Salles G, Lamy T, Béné MC, Raffoux E, Huguet F, Chevallier P, Bologna S, Bouabdallah R, Benichou J, Brière J, Moreau A, Tallon-Simon V, Seris S, Graux C, Asnafi V, Ifrah N, Macintyre E, Dombret H. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study. J Clin Oncol. 2016 Feb 20;34(6):572-80. Epub 2015 Dec 7. link to original article link to data supplement contains protocol PubMed NCT00195871

Daunorubicin, Pegaspargase, Vincristine, Dexamethasone

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Regimen, modified ABFM

Study Evidence
Vora et al. 2013 (UKALL 2003) Non-randomized portion of RCT

Chemotherapy

CNS prophylaxis

  • Cytarabine (Ara-C) as follows:
    • Ages 1 to 1.99: 30 mg IT once on day 1
    • Ages 2 to 2.99: 50 mg IT once on day 1
    • Age 3 and older: 70 mg IT once on day 1
  • Methotrexate (MTX) as follows:
    • Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29
    • Ages 2 to 2.99: 10 mg IT once per day on days 8 & 29
    • Ages 3 to 8.99: 12 mg IT once per day on days 8 & 29
    • Age 9 and older: 15 mg IT once per day on days 8 & 29

4-week course

Subsequent treatment

References

  1. UKALL 2003: Vora A, Goulden N, Wade R, Mitchell C, Hancock J, Hough R, Rowntree C, Richards S. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013 Mar;14(3):199-209. link to original article PubMed ISRCTN07355119

Consolidation after upfront therapy

Etoposide & TBI, then allo HSCT

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Regimen

Study Evidence
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) Non-randomized portion of RCT

Chemotherapy

Radiotherapy

Immunotherapy

Stem cells transfused on day 0

References

  1. MRC UKALL XII/ECOG E2993: Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. link to original article contains verified protocol PubMed
    1. Update: Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. link to original article PubMed
    2. Update: Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. link to original article link to PMC article PubMed
    3. Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article contains verified protocol link to PMC article PubMed

Relapsed or refractory

Nelarabine monotherapy

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Regimen variant #1, 5-day dosing

Study Years of enrollment Evidence Efficacy
Berg et al. 2005 1997-2002 Phase II (RT) ORR: 14-55%
Zwaan et al. 2017 (GSK 111081) 2009-2014 Phase IV ORR: 39%

Chemotherapy

21-day cycles

Regimen variant #2, intermittent dosing

Study Years of enrollment Evidence Efficacy
DeAngelo et al. 2007 (CALGB 19801) 1998-2001 Phase II (RT) ORR: 41% (95% CI, 15-43)

See paper for details about the schedule.

Chemotherapy

21-day cycle for 3 to 4 cycles (or delayed for count recovery)

References

  1. Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, Billett A, Kurtzberg J, Reaman G, Gaynon P, Whitlock J, Krailo M, Harris MB; Children's Oncology Group. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol. 2005 May 20;23(15):3376-82. link to original article contains protocol PubMed
  2. CALGB 19801: DeAngelo DJ, Yu D, Johnson JL, Coutre SE, Stone RM, Stopeck AT, Gockerman JP, Mitchell BS, Appelbaum FR, Larson RA. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007 Jun 15;109(12):5136-42. Epub 2007 Mar 7. link to original article contains verified protocol link to PMC article PubMed
  3. GSK 111081: Zwaan CM, Kowalczyk J, Schmitt C, Bielorai B, Russo MW, Woessner M, Ranganathan S, Leverger G. Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study. Br J Haematol. 2017 Oct;179(2):284-293. Epub 2017 Aug 2. link to original article contains verified protocol PubMed