PMID- 35738024
OWN - NLM
STAT- MEDLINE
DCOM- 20220726
LR  - 20220727
IS  - 1873-5835 (Electronic)
IS  - 0145-2126 (Linking)
VI  - 119
DP  - 2022 Aug
TI  - Clinical experience with frontline Hyper-CVAD-based regimens, including 
      Hyper-CVAD plus ponatinib, in patients with acute lymphoblastic leukemia treated 
      at a comprehensive cancer center.
PG  - 106885
LID - S0145-2126(22)00111-4 [pii]
LID - 10.1016/j.leukres.2022.106885 [doi]
AB  - BACKGROUND: Hyper-CVAD is an established regimen for adult ALL that was developed 
      at the MD Anderson Cancer Center (MDACC). However, results can vary across 
      different institutions given the heterogeneity of patient populations and 
      institutional practices. Moreover, while a MDACC study demonstrated that the 
      combination of ponatinib plus hyper-CVAD produced remarkable activity in 
      untreated Ph+ ALL, it remains to be externally validated. We sought to validate 
      those findings in previously untreated adult patients with Ph+ ALL. METHODS: This 
      was a retrospective study analyzing the outcomes of previously untreated adult 
      ALL patients treated with hyper-CVAD, with a focus on Ph+ ALL patients treated 
      with ponatinib plus hyper-CVAD. RESULTS: 82 patients were included. The median 
      age was 51 years. The median follow-up was 2.62 years. The 5-year overall 
      survival (OS) and event-free survival (EFS) were 39.5 % and 28.2 %, respectively. 
      For Ph+ ALL patients (n = 13) receiving ponatinib plus hyper-CVAD, 3-year OS and 
      EFS were both 92.3 %. Univariate analysis showed a high WBC and poor-risk 
      cytogenetics to be associated with inferior outcomes, while CD20 + predicted 
      favorable outcomes in B-ALL patients. On multivariate analysis, CD20 + retained 
      significance for Philadelphia-negative (Ph-) ALL. For Ph+ ALL, ponatinib was 
      associated with better OS and EFS on univariate and multivariate analysis. 
      CONCLUSION: Our data supports the use of ponatinib plus hyper-CVAD as a standard 
      of care regimen for Ph+ ALL. Our outcomes for Ph-ALL and T-cell ALL (T-ALL) show 
      that advances are still needed in the frontline setting, and clinical trial 
      enrollment is recommended.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Othman, Tamer
AU  - Othman T
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Moskoff, Benjamin N
AU  - Moskoff BN
AD  - Pharmacy Department, University of California Davis School of Medicine, 
      Sacramento, CA, USA.
FAU - Ho, Gwendolyn
AU  - Ho G
AD  - Department of Hematology Oncology, The Permanente Medical Group, Kaiser 
      Permanente, Sacramento, CA, USA.
FAU - Tenold, Matthew E
AU  - Tenold ME
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Azenkot, Tali
AU  - Azenkot T
AD  - Department of Internal Medicine, University of California Davis School of 
      Medicine, Sacramento, CA, USA.
FAU - Krackeler, Margaret L
AU  - Krackeler ML
AD  - Department of Internal Medicine, University of California Davis School of 
      Medicine, Sacramento, CA, USA.
FAU - Fisch, Samantha C
AU  - Fisch SC
AD  - University of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Potter, Laura A
AU  - Potter LA
AD  - University of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Kaesberg, Paul R
AU  - Kaesberg PR
AD  - Pharmacy Department, University of California Davis School of Medicine, 
      Sacramento, CA, USA.
FAU - Welborn, Jeanna L
AU  - Welborn JL
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Wun, Ted
AU  - Wun T
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Esteghamat, Naseem S
AU  - Esteghamat NS
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Hoeg, Rasmus T
AU  - Hoeg RT
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Rosenberg, Aaron S
AU  - Rosenberg AS
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Abedi, Mehrdad
AU  - Abedi M
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Tuscano, Joseph M
AU  - Tuscano JM
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA.
FAU - Jonas, Brian A
AU  - Jonas BA
AD  - Department of Internal Medicine, Division of Hematology and Oncology, University 
      of California Davis School of Medicine, Sacramento, CA, USA. Electronic address: 
      bajonas@ucdavis.edu.
LA  - eng
GR  - P30 CA093373/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20220608
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (Imidazoles)
RN  - 0 (Pyridazines)
RN  - 4340891KFS (ponatinib)
RN  - 5J49Q6B70F (Vincristine)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 80168379AG (Doxorubicin)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Adult
MH  - *Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Cyclophosphamide/therapeutic use
MH  - Dexamethasone/therapeutic use
MH  - Doxorubicin/therapeutic use
MH  - Humans
MH  - Imidazoles
MH  - Middle Aged
MH  - *Philadelphia Chromosome
MH  - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
MH  - Pyridazines
MH  - Retrospective Studies
MH  - Vincristine/therapeutic use
OTO - NOTNLM
OT  - ALL
OT  - Acute lymphoblastic leukemia
OT  - Hyper-CVAD
OT  - Ponatinib
OT  - TKI
OT  - Tyrosine kinase inhibitor
EDAT- 2022/06/24 06:00
MHDA- 2022/07/27 06:00
CRDT- 2022/06/23 18:12
PHST- 2022/02/21 00:00 [received]
PHST- 2022/05/22 00:00 [revised]
PHST- 2022/06/01 00:00 [accepted]
PHST- 2022/06/24 06:00 [pubmed]
PHST- 2022/07/27 06:00 [medline]
PHST- 2022/06/23 18:12 [entrez]
AID - S0145-2126(22)00111-4 [pii]
AID - 10.1016/j.leukres.2022.106885 [doi]
PST - ppublish
SO  - Leuk Res. 2022 Aug;119:106885. doi: 10.1016/j.leukres.2022.106885. Epub 2022 Jun 
      8.