Difference between revisions of "T-cell acute lymphoblastic leukemia"
Warner-admin (talk | contribs) m (Text replacement - "http://onlinelibrary.wiley.com" to "https://onlinelibrary.wiley.com") |
Warner-admin (talk | contribs) m (Text replacement - "*Cranial irradiation" to "*Whole-brain irradiation") |
||
Line 201: | Line 201: | ||
====CNS prophylaxis==== | ====CNS prophylaxis==== | ||
*[[Methotrexate (MTX)]] (dose not specified) IT on days 15, 22, 57, 64 | *[[Methotrexate (MTX)]] (dose not specified) IT on days 15, 22, 57, 64 | ||
− | * | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] in some arms (see paper for details) |
'''One course''' | '''One course''' | ||
Line 242: | Line 242: | ||
====CNS prophylaxis==== | ====CNS prophylaxis==== | ||
*[[Methotrexate (MTX)]] (dose not specified) IT on days 15, 22, 57, 64 | *[[Methotrexate (MTX)]] (dose not specified) IT on days 15, 22, 57, 64 | ||
− | * | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] in some arms (see paper for details) |
'''One course''' | '''One course''' |
Revision as of 02:10, 14 June 2018
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
back to top |
Regimen
Study | Evidence |
---|---|
Lepretre et al. 2015 (GRAALL-LYSA LL03) | Phase II |
Chemotherapy
- Prednisone (Sterapred) 60 mg/m2/day on days -7 to -1
CNS treatment
- Methotrexate (MTX) 15 mg IT once at some point between days -7 and -4
Patients then proceed to cyclophosphamide, daunorubicin, L-asparaginase, vincristine, prednisone reinforced induction.
References
- 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
back to top |
Regimen, modified ABFM
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
See note (COG AALL1231) | Phase III | 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
- Daunorubicin (Cerubidine) 25 mg/m2 IV push 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
- Dexamethasone (Decadron) 3 mg/m2 PO or IV BID on days 1 to 28
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
Treatment followed by cyclophosphamide, cytarabine, mercaptopurine, pegaspargase, vincristine consolidation. Bone marrow biopsy is required after induction, to determine post-consolidation risk stratification and therapy.
References
- 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
- COG AALL1231: TBD, see note
Daunorubicin, Pegaspargase, Vincristine, Prednisone
back to top |
Regimen
Study | Evidence |
---|---|
Winter et al. 2015 (COG AALL0434) | Non-randomized portion of RCT |
Chemotherapy
- Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 1, 8, 15, 22
- Pegaspargase (Oncaspar) 2500 units/m2 IV once on day 4, 5, OR 6 (1 dose)
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
- Prednisone (Sterapred) 30 mg/m2 PO BID on days 1 to 28
4-week course
Subsequent treatment
- Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine versus Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine
References
- 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
back to top |
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
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 3 hours once on day 1, then 500 mg/m2 IV q12h 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
- Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 14
Supportive medications
- Lenograstim (Granocyte) 150 mcg/m2 SC once per day from day 17 until myeloid recovery
CNS prophylaxis
- Methotrexate (MTX) 15 mg IT once per day on days 1 & 8
- Cytarabine (Cytosar) 40 mg IT once per day on days 1 & 8
- Methylprednisolone (Depo-Medrol) 40 mg IT once per day on days 1 & 8
One course
See paper for details beyond induction.
References
- 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
Allogeneic hematopoietic stem cell transplant
back to top |
Regimen
To be completed
References
- 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
Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine
back to top |
Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | Phase III | 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
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 8 & 50
- Cytarabine (Cytosar) 75 mg/m2 IV/SC once per day on days 8 to 11, 15 to 18, 50 to 53, 57 to 60
- Mercaptopurine (Purinethol) 60 mg/m2 PO once per day on days 8 to 21, 50 to 63
- Nelarabine (Arranon) 650 mg/m2 IV once per day on days 1 to 5, 43 to 47
- Pegaspargase (Oncaspar) 2500 units/m2 IM once per day on days 22 & 64
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 22, 64, 71
CNS prophylaxis
- Methotrexate (MTX) (dose not specified) IT on days 15, 22, 57, 64
- Whole-brain irradiation in some arms (see paper for details)
One course
Subsequent treatment
- Interim maintenance; see paper for details
References
- 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
back to top |
Variant #1
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | Phase III | 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
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 8 & 50
- Cytarabine (Cytosar) 75 mg/m2 IV/SC once per day on days 8 to 11, 15 to 18, 50 to 53, 57 to 60
- Mercaptopurine (Purinethol) 60 mg/m2 PO once per day on days 8 to 21, 50 to 63
- Pegaspargase (Oncaspar) 2500 units/m2 IM once per day on days 22 & 64
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 22, 64, 71
CNS prophylaxis
- Methotrexate (MTX) (dose not specified) IT on days 15, 22, 57, 64
- Whole-brain irradiation in some arms (see paper for details)
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
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 29
- Cytarabine (Cytosar) 75 mg/m2 IV or SC once per day on days 1 to 4, 8 to 11, 29 to 32, 36 to 39
- Mercaptopurine (Purinethol) 60 mg/m2 PO once per day on days 1 to 14, 29 to 42
- Dose may be modified based on TPMT status
- Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once per day on days 15 & 43
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50
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
- 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
- COG AALL1231: TBD, see note
Consolidation after salvage therapy
Allogeneic hematopoietic stem cell transplant
To be completed
Relapsed or refractory
Mitoxantrone, Pegaspargase, Vincristine, Dexamethasone
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Parker et al. 2010 (UK ALL R3) | Phase III, <20 pts in this subgroup | 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
- Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 & 8
- Pegaspargase (Oncaspar) 1000 units/m2 IM once per day on days 3 & 18
- Allergic patients: Asparaginase Erwinia chrysanthemi (Erwinaze) 20,000 units IM once per day on days 3, 5, 7, 9, 11, 13, 18, 20, 22, 24, 26, 28
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 3, 10, 17, 24
- Dexamethasone (Decadron) 20 mg/m2 PO once per day on days 1 to 5, 15 to 19
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
See paper for details of treatment beyond induction.
References
- 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
back to top |
Variant #1, 5-day dosing
Study | Evidence | Efficacy |
---|---|---|
Zwaan et al. 2017 | Phase IV | ORR: 39% |
Chemotherapy
- Nelarabine (Arranon) 650 mg/m2 IV over 60 minutes once per day on days 1 to 5
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
- 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
- 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
- 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