T-cell acute lymphoblastic leukemia

Section editor		Section editor
	Bhagirathbhai Dholaria, MBBS Vanderbilt University Nashville, TN, USA LinkedIn		Ashwin Kishtagari, MD Vanderbilt University Nashville, TN, USA LinkedIn

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:

• Pediatric T-cell ALL

• We have moved How I Treat articles to a dedicated page.

5 regimens on this page 6 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

• NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Acute Lymphoblastic Leukemia.
• 2021: Brown et al. Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. PubMed

Pre-phase

Prednisone monotherapy

Regimen

Study	Evidence
Lepretre et al. 2015 (GRAALL-LYSA LL03)	Phase 2

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m²/day PO on days -7 to -1

CNS therapy, prophylaxis

• Methotrexate (MTX) 15 mg IT once at some point between days -7 and -4

7-day course

Subsequent treatment

• Cyclophosphamide, daunorubicin, L-asparaginase, vincristine, prednisone re-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 dosing details in abstract PubMed NCT00195871

Upfront induction therapy

Cyclophosphamide, Daunorubicin, L-Asparaginase, Vincristine, Prednisone

Regimen, "Pediatric-like GRAALL reinforced induction"

Study	Evidence
Lepretre et al. 2015 (GRAALL-LYSA LL03)	Phase 2

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

• Prednisone pre-phase

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV over 3 hours once on day 1, then 500 mg/m² IV every 12 hours on days 15 & 16
• Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1 to 3, then 30 mg/m² IV once per day on days 15 & 16
• Asparaginase (Elspar) 6000 units/m²/day (route not specified) on days 8, 10, 12, 20, 22, 24, 26, 28
• Vincristine (Oncovin) 2 mg IV once per day on days 1, 8, 15, 22

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m²/day PO on days 1 to 14

Supportive therapy

• Lenograstim (Granocyte) 150 mcg/m² SC once per day from day 17 until myeloid recovery

CNS therapy, prophylaxis

• Methotrexate (MTX) 15 mg IT once per day on days 1 & 8
• Cytarabine (Ara-C) 40 mg IT once per day on days 1 & 8
• Methylprednisolone (Depo-Medrol) 40 mg IT once per day on days 1 & 8

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 dosing details in abstract PubMed NCT00195871

Daunorubicin, Pegaspargase, Vincristine, Dexamethasone

Regimen, modified ABFM

Study	Dates of enrollment	Evidence
Vora et al. 2013 (UKALL 2003)	2003-2011	Non-randomized part of phase 2 RCT

Chemotherapy

• Daunorubicin (Cerubidine) 25 mg/m² IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
• Pegaspargase (Oncaspar) 2500 units/m² IV over 1 to 2 hours once per day on days 4 & 18
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22

Glucocorticoid therapy

• Dexamethasone (Decadron) 3 mg/m² IV or PO twice per day on days 1 to 28

CNS therapy, prophylaxis

• Cytarabine (Ara-C) by the following age-based criteria:
  • 1 to 1.99 years old: 30 mg IT once on day 1
  • 2 to 2.99 years old: 50 mg IT once on day 1
  • 3 years old or older: 70 mg IT once on day 1
• Methotrexate (MTX) by the following age-based criteria:
  • 1 to 1.99 years old: 8 mg IT once per day on days 8 & 29
  • 2 to 2.99 years old: 10 mg IT once per day on days 8 & 29
  • 3 to 8.99 years old: 12 mg IT once per day on days 8 & 29
  • 9 years old or older: 15 mg IT once per day on days 8 & 29

4-week course

Subsequent treatment

• Cyclophosphamide, cytarabine, mercaptopurine, pegaspargase, vincristine consolidation

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. Epub 2013 Feb 7. link to original article PubMed ISRCTN07355119

Consolidation after upfront therapy

Etoposide & TBI, then allo HSCT

Regimen

Study	Evidence
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993)	Non-randomized part of phase 3 RCT

Chemotherapy

• Etoposide (Vepesid) 60 mg/kg IV once on day -3

Radiotherapy

• Total body irradiation (TBI) 220 cGy twice per day in 6 fractions on days -6 to -4 (total dose: 1320 cGy)

Immunotherapy

• Allogeneic stem cells transfused on day 0

One course

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 dosing details in manuscript PubMed NCT00002514
   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 dosing details in manuscript link to PMC article PubMed

Relapsed or refractory

Nelarabine monotherapy

Regimen variant #1, 5-day dosing

Study	Dates of enrollment	Evidence	Efficacy
Berg et al. 2005	1997-2002	Phase 2 (RT)	ORR: 14-55%
Zwaan et al. 2017 (GSK 111081)	2009-2014	Phase 4	ORR: 39%

Chemotherapy

• Nelarabine (Arranon) 650 mg/m² IV over 60 minutes once per day on days 1 to 5

21-day cycles

Regimen variant #2, intermittent dosing

Study	Dates of enrollment	Evidence	Efficacy
DeAngelo et al. 2007 (CALGB 19801)	1998-2001	Phase 2 (RT)	ORR: 41% (95% CI, 15-43)

Note: See paper for details about the schedule.

Chemotherapy

• Nelarabine (Arranon) 1500 mg/m² IV over 2 hours once per day on days 1, 3, 5

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 dosing details in abstract 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 dosing details in manuscript 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 dosing details in manuscript PubMed NCT00866671