Difference between revisions of "T-cell acute lymphoblastic leukemia"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
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{| class="wikitable" style="text-align:center; width:100%;"
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{{#lst:Editorial board transclusions|t-all}}
! colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26" |'''Section editor'''
 
! colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26" |'''Section editor'''
 
|-
 
| style="background-color:#F0F0F0; width:15%" |[[File:MartinSchoen.jpg|frameless|upright=0.3|center]]
 
| style="width:35%" |<big>[[User:Marteens|Martin W. Schoen, MD, MPH]]<br>Saint Louis University<br>St. Louis, MO</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/mwschoen mwschoen]
 
|style="background-color:#F0F0F0; width:15%"|[[File:Bdholaria.jpg|frameless|upright=0.3|center]]
 
| style="width:35%" |<big>[[User:Bdholaria|Bhagirathbhai Dholaria, MBBS]]<br>Vanderbilt University<br>Nashville, TN</big>
 
|-
 
|}
 
 
<big>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).</big>
 
<big>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).</big>
 
<big>'''Note: certain regimens have been moved to dedicated pages:
 
<big>'''Note: certain regimens have been moved to dedicated pages:
 
*'''[[T-cell acute lymphoblastic leukemia, pediatric|Pediatric T-cell ALL]]
 
*'''[[T-cell acute lymphoblastic leukemia, pediatric|Pediatric T-cell ALL]]
 
</big>
 
</big>
 +
*''We have moved [[How I Treat]] articles to a dedicated page.''
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
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{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Guidelines=
 
=Guidelines=
=="How I Treat"==
+
'''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.'''
*'''2020:''' Aldoss I, Douer D. How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood. 2020 Mar 26;135(13):987-995. [https://doi.org/10.1182/blood.2019002477 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31977001 PubMed]
+
==NCCN==
 
+
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1410 NCCN Guidelines - Acute Lymphoblastic Leukemia].''
==[https://www.nccn.org/ NCCN]==
+
*'''2021:''' Brown et al. [https://doi.org/10.6004/Jnccn.2021.0042 Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/34551384/ PubMed]
*[https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf NCCN Guidelines - T-cell Lymphomas]
 
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_all.pdf NCCN Guidelines - Pediatric Acute Lymphoblastic Leukemia]
 
  
 
=Pre-phase=
 
=Pre-phase=
 
==Prednisone monotherapy {{#subobject:30c275|Regimen=1}}==
 
==Prednisone monotherapy {{#subobject:30c275|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:af8a3d|Variant=1}}===
 
===Regimen {{#subobject:af8a3d|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
 
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days -7 to -1
 
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days -7 to -1
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Methotrexate (MTX)]] 15 mg IT once at some point between days -7 and -4
 
*[[Methotrexate (MTX)]] 15 mg IT once at some point between days -7 and -4
 
 
'''7-day course'''
 
'''7-day course'''
 
+
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
*[[#Cyclophosphamide.2C_Daunorubicin.2C_L-Asparaginase.2C_Vincristine.2C_Prednisone|Cyclophosphamide, daunorubicin, L-asparaginase, vincristine, prednisone]] re-induction
 
*[[#Cyclophosphamide.2C_Daunorubicin.2C_L-Asparaginase.2C_Vincristine.2C_Prednisone|Cyclophosphamide, daunorubicin, L-asparaginase, vincristine, prednisone]] re-induction
 
+
</div></div>
 
===References===
 
===References===
 
<!-- Presented at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
 
<!-- Presented at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
#'''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. [https://doi.org/10.1200/JCO.2015.61.5385 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.61.5385 link to data supplement] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26644537 PubMed] NCT00195871
+
#'''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. [https://doi.org/10.1200/JCO.2015.61.5385 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.61.5385 link to data supplement] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26644537/ PubMed] [https://clinicaltrials.gov/study/NCT00195871 NCT00195871]
 
 
 
=Upfront induction therapy=
 
=Upfront induction therapy=
 
==Cyclophosphamide, Daunorubicin, L-Asparaginase, Vincristine, Prednisone {{#subobject:b90dc3|Regimen=1}}==
 
==Cyclophosphamide, Daunorubicin, L-Asparaginase, Vincristine, Prednisone {{#subobject:b90dc3|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
 
 
===Regimen, "Pediatric-like GRAALL reinforced induction" {{#subobject:56ea06|Variant=1}}===
 
===Regimen, "Pediatric-like GRAALL reinforced induction" {{#subobject:56ea06|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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|}
 
|}
 
''Note: This regimen was meant for patients less than 60 years old (up to age 59). Regimen is as per the [[Acute_lymphocytic_leukemia#Pediatric-like_GRAALL_induction|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.''
 
''Note: This regimen was meant for patients less than 60 years old (up to age 59). Regimen is as per the [[Acute_lymphocytic_leukemia#Pediatric-like_GRAALL_induction|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.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
*[[#Prednisone_monotherapy|Prednisone pre-phase]]
+
*[[#Prednisone_monotherapy|Prednisone]] pre-phase
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 3 hours once on day 1, then 500 mg/m<sup>2</sup> IV every 12 hours on days 15 & 16
 
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 3 hours once on day 1, then 500 mg/m<sup>2</sup> IV every 12 hours on days 15 & 16
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====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
 
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 14
 
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 14
 
 
====Supportive therapy====
 
====Supportive therapy====
 
*[[Lenograstim (Granocyte)]] 150 mcg/m<sup>2</sup> SC once per day from day 17 until myeloid recovery
 
*[[Lenograstim (Granocyte)]] 150 mcg/m<sup>2</sup> SC once per day from day 17 until myeloid recovery
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 1 & 8
 
*[[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
 
*[[Cytarabine (Ara-C)]] 40 mg IT once per day on days 1 & 8
 
*[[Methylprednisolone (Solumedrol)|Methylprednisolone (Depo-Medrol)]] 40 mg IT once per day on days 1 & 8
 
*[[Methylprednisolone (Solumedrol)|Methylprednisolone (Depo-Medrol)]] 40 mg IT once per day on days 1 & 8
 
 
'''28-day course'''
 
'''28-day course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
*See paper for details beyond induction
 
*See paper for details beyond induction
 
+
</div></div>
 
===References===
 
===References===
 
<!-- Presented at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
 
<!-- Presented at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
#'''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. [https://doi.org/10.1200/JCO.2015.61.5385 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.61.5385 link to data supplement] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26644537 PubMed] NCT00195871
+
#'''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. [https://doi.org/10.1200/JCO.2015.61.5385 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.61.5385 link to data supplement] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26644537/ PubMed] [https://clinicaltrials.gov/study/NCT00195871 NCT00195871]
 
 
 
==Daunorubicin, Pegaspargase, Vincristine, Dexamethasone {{#subobject:516f7b|Regimen=1}}==
 
==Daunorubicin, Pegaspargase, Vincristine, Dexamethasone {{#subobject:516f7b|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen, modified ABFM {{#subobject:88f520|Variant=1}}===
 
===Regimen, modified ABFM {{#subobject:88f520|Variant=1}}===
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
!style="width: 50%"|Study
+
!style="width: 33%"|Study
!style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://doi.org/10.1016/S1470-2045(12)70600-9 Vora et al. 2013 (UKALL 2003)]
 
|[https://doi.org/10.1016/S1470-2045(12)70600-9 Vora et al. 2013 (UKALL 2003)]
| style="background-color:#91cf61" |Non-randomized portion of RCT
+
|2003-2011
 +
| style="background-color:#91cf61" |Non-randomized part of phase 2 RCT
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
 
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
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====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
 
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 28
 
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 28
 
 
====CNS therapy, prophylaxis====
 
====CNS therapy, prophylaxis====
 
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
**Ages 1 to 1.99: 30 mg IT once on day 1
+
**1 to 1.99 years old: 30 mg IT once on day 1
**Ages 2 to 2.99: 50 mg IT once on day 1
+
**2 to 2.99 years old: 50 mg IT once on day 1
**Age 3 and older: 70 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:
 
*[[Methotrexate (MTX)]] by the following age-based criteria:
**Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29
+
**1 to 1.99 years old: 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
+
**2 to 2.99 years old: 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
+
**3 to 8.99 years old: 12 mg IT once per day on days 8 & 29
**Age 9 and older: 15 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'''
 
'''4-week course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
 
*[[#Cyclophosphamide.2C_Cytarabine.2C_Mercaptopurine.2C_Pegaspargase.2C_Vincristine|Cyclophosphamide, cytarabine, mercaptopurine, pegaspargase, vincristine]] consolidation
 
*[[#Cyclophosphamide.2C_Cytarabine.2C_Mercaptopurine.2C_Pegaspargase.2C_Vincristine|Cyclophosphamide, cytarabine, mercaptopurine, pegaspargase, vincristine]] consolidation
 +
</div></div>
  
 
===References===
 
===References===
# '''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. [https://doi.org/10.1016/S1470-2045(12)70600-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23395119 PubMed] ISRCTN07355119
+
# '''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. [https://doi.org/10.1016/S1470-2045(12)70600-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23395119/ PubMed] ISRCTN07355119
  
 
=Consolidation after upfront therapy=
 
=Consolidation after upfront therapy=
 
 
==Etoposide & TBI, then allo HSCT {{#subobject:b389e1|Regimen=1}}==
 
==Etoposide & TBI, then allo HSCT {{#subobject:b389e1|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:e4216b|Variant=1}}===
 
===Regimen {{#subobject:e4216b|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
|[http://www.bloodjournal.org/content/106/12/3760.long Rowe et al. 2005 (MRC UKALL XII/ECOG E2993)]
+
|[https://doi.org/10.1182/blood-2005-04-1623 Rowe et al. 2005 (MRC UKALL XII/ECOG E2993)]
| style="background-color:#91cf61" |Non-randomized portion of RCT
+
| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 
|-
 
|-
 
|}
 
|}
 
{{#lst:Allogeneic HSCT|e4216b}}
 
{{#lst:Allogeneic HSCT|e4216b}}
====Immunotherapy====
+
</div></div>
*[[Allogeneic stem cells]]
 
'''Stem cells transfused on day 0'''
 
 
===References===
 
===References===
# '''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. [http://www.bloodjournal.org/content/106/12/3760.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16105981 PubMed] NCT00002514
+
# '''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. [https://doi.org/10.1182/blood-2005-04-1623 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16105981/ PubMed] [https://clinicaltrials.gov/study/NCT00002514 NCT00002514]
## '''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. [http://www.bloodjournal.org/content/111/4/1827.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/18048644 PubMed]  
+
## '''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. [https://doi.org/10.1182/blood-2007-10-116582 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18048644/ PubMed]  
## '''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. [http://www.bloodjournal.org/content/113/19/4489.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188540/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19244158 PubMed]  
+
## '''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. [https://doi.org/10.1182/blood-2009-01-199380 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188540/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19244158/ PubMed]  
## '''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. [http://www.bloodjournal.org/content/123/6/843.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916877/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24277073 PubMed]
+
## '''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. [https://doi.org/10.1182/blood-2013-09-529008 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916877/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24277073/ PubMed]
  
 
=Relapsed or refractory=
 
=Relapsed or refractory=
 
 
==Nelarabine monotherapy {{#subobject:bb7a38|Regimen=1}}==
 
==Nelarabine monotherapy {{#subobject:bb7a38|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #1, 5-day dosing {{#subobject:44a025|Variant=1}}===
 
===Regimen variant #1, 5-day dosing {{#subobject:44a025|Variant=1}}===
 
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
!style="width: 25%"|Years of enrollment
+
!style="width: 25%"|Dates of enrollment
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
Line 179: Line 168:
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Nelarabine (Arranon)]] 650 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
*[[Nelarabine (Arranon)]] 650 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
 
'''21-day cycles'''
 
'''21-day cycles'''
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #2, intermittent dosing {{#subobject:b5ce00|Variant=1}}===
 
===Regimen variant #2, intermittent dosing {{#subobject:b5ce00|Variant=1}}===
 
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
!style="width: 25%"|Years of enrollment
+
!style="width: 25%"|Dates of enrollment
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
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|-
 
|-
 
|}
 
|}
''See paper for details about the schedule.''
+
''Note: See paper for details about the schedule.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Nelarabine (Arranon)]] 1500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 3, 5
 
*[[Nelarabine (Arranon)]] 1500 mg/m<sup>2</sup> 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)'''
 
'''21-day cycle for 3 to 4 cycles (or delayed for count recovery)'''
 
+
</div></div>
 
===References===
 
===References===
# 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. [https://doi.org/10.1200/JCO.2005.03.426 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15908649 PubMed]
+
# 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. [https://doi.org/10.1200/JCO.2005.03.426 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15908649/ PubMed]
# '''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. [http://www.bloodjournal.org/content/109/12/5136.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1941786/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17344466 PubMed]
+
# '''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. [https://doi.org/10.1182/blood-2006-11-056754 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1941786/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17344466/ PubMed]
# '''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. [https://doi.org/10.1111/bjh.14874 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28771663 PubMed] NCT00866671
+
# '''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. [https://doi.org/10.1111/bjh.14874 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28771663/ PubMed] [https://clinicaltrials.gov/study/NCT00866671 NCT00866671]
 
 
 
[[Category:T-cell acute lymphoblastic leukemia regimens]]
 
[[Category:T-cell acute lymphoblastic leukemia regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Acute lymphoblastic leukemias]]
 
[[Category:Acute lymphoblastic leukemias]]
 
[[Category:T-cell leukemias]]
 
[[Category:T-cell leukemias]]

Latest revision as of 01:37, 26 June 2024

Section editor Section editor
Bdholaria.jpg
Bhagirathbhai Dholaria, MBBS
Vanderbilt University
Nashville, TN, USA

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Ashwin Kishtagari, MD
Vanderbilt University
Nashville, TN, USA

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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:

  • 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

Pre-phase

Prednisone monotherapy

Regimen

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

Glucocorticoid therapy

CNS therapy, prophylaxis

7-day course

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

Chemotherapy

Glucocorticoid therapy

Supportive therapy

CNS therapy, 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 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

Glucocorticoid therapy

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

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

Radiotherapy

Immunotherapy

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

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

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