T-cell acute lymphoblastic leukemia

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5 regimens on this page
6 variants on this page


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).

Guidelines

NCCN

Pre-phase

Prednisone monotherapy

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Regimen

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

Chemotherapy

CNS treatment

7-day course

Subsequent treatment

References

  1. 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

Upfront induction therapy

Daunorubicin, Pegaspargase, Vincristine, Dexamethasone

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Regimen, modified ABFM

Study Evidence Comparator Efficacy
See note (COG AALL1231) Phase III (C) Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone, Bortezomib TBD

Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age. It is based on the UKALL 2003 backbone, although there are some differences.

Chemotherapy

CNS prophylaxis

  • Cytarabine (Cytosar) 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
  2. COG AALL1231: TBD, see note

Daunorubicin, Pegaspargase, Vincristine, Prednisone

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Regimen

Study Evidence
Winter et al. 2015 (COG AALL0434) Non-randomized portion of RCT

Chemotherapy

4-week course

Subsequent treatment

References

  1. Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed

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

One course

Subsequent treatment

  • See paper for details beyond induction

References

  1. 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

Consolidation after upfront therapy

Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine

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Regimen

Study Evidence Comparator Efficacy Toxicity
Winter et al. 2015 (COG AALL0434) Phase III (E) Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine Not reported Similar toxicity

Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.

Preceding treatment

Chemotherapy

CNS prophylaxis

One course

Subsequent treatment

  • Interim maintenance; see paper for details

References

  1. Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed

Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine

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Variant #1

Study Evidence Comparator Efficacy Toxicity
Winter et al. 2015 (COG AALL0434) Phase III (C) Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine Not reported Similar toxicity

Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.

Preceding treatment

Chemotherapy

CNS prophylaxis

One course

Subsequent treatment

  • Interim maintenance; see paper for details

Variant #2

Study Evidence
See note (COG AALL1231) Non-randomized portion of RCT

Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.

Preceding treatment

Chemotherapy

Supportive medications

  • Mesna (Mesnex) "is not required for this dose of cyclophosphamide, but may be administered at institutional discretion."

CNS prophylaxis

  • Methotrexate (MTX) as follows, for CNS3:
    • Ages 1 to 1.99: 8 mg IT once per day on days 1 & 8
    • Ages 2 to 2.99: 10 mg IT once per day on days 1 & 8
    • Ages 3 to 8.99: 12 mg IT once per day on days 1 & 8
    • Age 9 and older: 15 mg IT once per day on days 1 & 8

One course

See protocol for details of treatment beyond consolidation, which is guided by MRD status obtained at the end of induction.

References

  1. Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed
  2. COG AALL1231: TBD, see note

Etoposide & TBI, then allo HSCT

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Variant #1

Study Evidence
Peters et al. 2015 (ALL-SCT-BFM 2003) Non-randomized

Chemotherapy

Radiotherapy

Immunotherapy

One course

Variant #2

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

Chemotherapy

Radiotherapy

Immunotherapy

One course

References

  1. ALL-BFM 90: Schrappe M, Reiter A, Ludwig WD, Harbott J, Zimmermann M, Hiddemann W, Niemeyer C, Henze G, Feldges A, Zintl F, Kornhuber B, Ritter J, Welte K, Gadner H, Riehm H; German-Austrian-Swiss ALL-BFM Study Group. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. Blood. 2000 Jun 1;95(11):3310-22. link to original article contains verified protocol PubMed
    1. Subgroup analysis: Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, Peters C, Ebell W, Zimmermann M, Niggli F, Ludwig WD, Riehm H, Welte K, Schrappe M. Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol. 2006 Dec 20;24(36):5742-9. link to original article PubMed
  2. 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
  3. ALL-BFM 95: Möricke A, Reiter A, Zimmermann M, Gadner H, Stanulla M, Dördelmann M, Löning L, Beier R, Ludwig WD, Ratei R, Harbott J, Boos J, Mann G, Niggli F, Feldges A, Henze G, Welte K, Beck JD, Klingebiel T, Niemeyer C, Zintl F, Bode U, Urban C, Wehinger H, Niethammer D, Riehm H, Schrappe M; German-Austrian-Swiss ALL-BFM Study Group. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. Blood. 2008 May 1;111(9):4477-89. Epub 2008 Feb 19. Erratum in: Blood. 2009 Apr 30;113(18):4478. Dosage error in article text. link to original article contains verified protocol PubMed
    1. Subgroup analysis: Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, Peters C, Ebell W, Zimmermann M, Niggli F, Ludwig WD, Riehm H, Welte K, Schrappe M. Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol. 2006 Dec 20;24(36):5742-9. link to original article PubMed
  4. ALL-SCT-BFM-2003: Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. Epub 2015 Mar 9. link to original article PubMed

Consolidation after salvage therapy

Allogeneic hematopoietic stem cell transplant

To be completed

Relapsed or refractory

Mitoxantrone, Pegaspargase, Vincristine, Dexamethasone

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Regimen

Study Evidence Comparator Efficacy
Parker et al. 2010 (UK ALL R3) Phase III, <20 pts in this subgroup (E) Idarubicin, Pegaspargase, Vincristine, Dexamethasone Seems not superior

Note: per the protocol, this regimen is intended only for patients 18 and younger. This is the same regimen used in relapsed B-ALL, but this subgroup did not have a statistically significant difference between the regimens.

Chemotherapy

CNS prophylaxis

  • Methotrexate (MTX) as follows:
    • Age less than 2: 8 mg IT once per day on days 1 & 8
    • Age 2: 10 mg IT once per day on days 1 & 8
    • Age older than 2: 12 mg IT once per day on days 1 & 8

4-week course

Subsequent treatment

  • See paper for details of treatment beyond induction

References

  1. Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Révész T, Darbyshire P, Love S, Saha V. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010 Dec 11;376(9757):2009-17. Epub 2010 Dec 3. link to original article contains verified protocol link to PMC article PubMed

Nelarabine monotherapy

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Variant #1, 5-day dosing

Study Evidence Efficacy
Zwaan et al. 2017 Phase IV ORR: 39%

Chemotherapy

21-day cycles

Variant #2, intermittent dosing

Study Evidence Efficacy
DeAngelo et al. 2007 (CALGB 19801) Phase II 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. 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
  2. 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
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