Association of HLA phenotype and response to interferon-alpha in patients with chronic myelogenous leukemia

J. Cortes, L. Fayad, H. Kantarjian, S. O'Brien, M. S. Lee, M. Talpaz

Research output: Contribution to journalArticle

Abstract

Twenty to 25% of patients with chronic myelogenous leukemia (CML) treated with interferon-alpha (IFN-A) achieve a complete cytogenetic response (CCR). However, cells bearing rearrangement of BCR/ABL can still be detected many years after achieving a CCR despite the absence of clinical evidence of active disease. It has been suggested that the disease is kept in a dormant state by immune mechanisms. How this is achieved is not known, but it has been speculated that p210(BCR/ABL) might be presented by malignant cells through HLA molecules, thus making them the target for specific immune cell killing. Because specific peptides will be expressed in association with certain HLA molecules, different HLA phenotypes could be associated with different response rates to IFN-A. The response to IFN-A-based therapies in 239 patients with chronic phase CML was analyzed according to their HLA phenotype. One hundred and ninety-four (81%) achieved complete hematologic response, 142 (59%) had a cytogenetic response which was major (MCR) in 93 patients (39%): complete (CCR) in 71 (30%) and partial (PCR) in 22 (9%). Patients with an HLA-B27 phenotype had the best response rate to IFN-A: 10 of 14 (71%) had an MCR, including eight (57%) with a CCR (P = 0.02). Patients with HLA-B35, -A3, and -A31 also showed a trend towards a higher response rate, whereas patients with HLA-B18 had the lowest response rate (MCR 17%). Patients with HLA-B27 and those with HLA-A31 showed a trend for better survival, whereas patients with HLA-A2, -B7, or -B18 had a trend for shorter survival. We conclude that response to IFN-A in patients with CML may be associated with the HLA phenotype. However, a much larger population would be required to determine if the impact of HLA phenotype on survival is independent of other clinical prognostic features. These findings could be relevant for the understanding of immune mechanisms of control of CML and possibly the design of immune therapy for this disease.

Original languageEnglish (US)
Pages (from-to)455-462
Number of pages8
JournalLeukemia
Volume12
Issue number4
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferon-alpha
Phenotype
Cytogenetics
HLA-B27 Antigen
Survival
HLA-B18 Antigen
HLA-B35 Antigen
HLA-A3 Antigen
HLA-B7 Antigen
Leukemia, Myeloid, Chronic Phase
HLA-A2 Antigen
Immune System Diseases
Polymerase Chain Reaction
Peptides
Therapeutics

Keywords

  • Chronic myelogenous leukemia
  • HLA
  • Interferon-alpha

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Association of HLA phenotype and response to interferon-alpha in patients with chronic myelogenous leukemia. / Cortes, J.; Fayad, L.; Kantarjian, H.; O'Brien, S.; Lee, M. S.; Talpaz, M.

In: Leukemia, Vol. 12, No. 4, 01.01.1998, p. 455-462.

Research output: Contribution to journalArticle

Cortes, J. ; Fayad, L. ; Kantarjian, H. ; O'Brien, S. ; Lee, M. S. ; Talpaz, M. / Association of HLA phenotype and response to interferon-alpha in patients with chronic myelogenous leukemia. In: Leukemia. 1998 ; Vol. 12, No. 4. pp. 455-462.
@article{bf7e24c2b13b4d93b978a360ff1322ac,
title = "Association of HLA phenotype and response to interferon-alpha in patients with chronic myelogenous leukemia",
abstract = "Twenty to 25{\%} of patients with chronic myelogenous leukemia (CML) treated with interferon-alpha (IFN-A) achieve a complete cytogenetic response (CCR). However, cells bearing rearrangement of BCR/ABL can still be detected many years after achieving a CCR despite the absence of clinical evidence of active disease. It has been suggested that the disease is kept in a dormant state by immune mechanisms. How this is achieved is not known, but it has been speculated that p210(BCR/ABL) might be presented by malignant cells through HLA molecules, thus making them the target for specific immune cell killing. Because specific peptides will be expressed in association with certain HLA molecules, different HLA phenotypes could be associated with different response rates to IFN-A. The response to IFN-A-based therapies in 239 patients with chronic phase CML was analyzed according to their HLA phenotype. One hundred and ninety-four (81{\%}) achieved complete hematologic response, 142 (59{\%}) had a cytogenetic response which was major (MCR) in 93 patients (39{\%}): complete (CCR) in 71 (30{\%}) and partial (PCR) in 22 (9{\%}). Patients with an HLA-B27 phenotype had the best response rate to IFN-A: 10 of 14 (71{\%}) had an MCR, including eight (57{\%}) with a CCR (P = 0.02). Patients with HLA-B35, -A3, and -A31 also showed a trend towards a higher response rate, whereas patients with HLA-B18 had the lowest response rate (MCR 17{\%}). Patients with HLA-B27 and those with HLA-A31 showed a trend for better survival, whereas patients with HLA-A2, -B7, or -B18 had a trend for shorter survival. We conclude that response to IFN-A in patients with CML may be associated with the HLA phenotype. However, a much larger population would be required to determine if the impact of HLA phenotype on survival is independent of other clinical prognostic features. These findings could be relevant for the understanding of immune mechanisms of control of CML and possibly the design of immune therapy for this disease.",
keywords = "Chronic myelogenous leukemia, HLA, Interferon-alpha",
author = "J. Cortes and L. Fayad and H. Kantarjian and S. O'Brien and Lee, {M. S.} and M. Talpaz",
year = "1998",
month = "1",
day = "1",
doi = "10.1038/sj.leu.2400965",
language = "English (US)",
volume = "12",
pages = "455--462",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Association of HLA phenotype and response to interferon-alpha in patients with chronic myelogenous leukemia

AU - Cortes, J.

AU - Fayad, L.

AU - Kantarjian, H.

AU - O'Brien, S.

AU - Lee, M. S.

AU - Talpaz, M.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Twenty to 25% of patients with chronic myelogenous leukemia (CML) treated with interferon-alpha (IFN-A) achieve a complete cytogenetic response (CCR). However, cells bearing rearrangement of BCR/ABL can still be detected many years after achieving a CCR despite the absence of clinical evidence of active disease. It has been suggested that the disease is kept in a dormant state by immune mechanisms. How this is achieved is not known, but it has been speculated that p210(BCR/ABL) might be presented by malignant cells through HLA molecules, thus making them the target for specific immune cell killing. Because specific peptides will be expressed in association with certain HLA molecules, different HLA phenotypes could be associated with different response rates to IFN-A. The response to IFN-A-based therapies in 239 patients with chronic phase CML was analyzed according to their HLA phenotype. One hundred and ninety-four (81%) achieved complete hematologic response, 142 (59%) had a cytogenetic response which was major (MCR) in 93 patients (39%): complete (CCR) in 71 (30%) and partial (PCR) in 22 (9%). Patients with an HLA-B27 phenotype had the best response rate to IFN-A: 10 of 14 (71%) had an MCR, including eight (57%) with a CCR (P = 0.02). Patients with HLA-B35, -A3, and -A31 also showed a trend towards a higher response rate, whereas patients with HLA-B18 had the lowest response rate (MCR 17%). Patients with HLA-B27 and those with HLA-A31 showed a trend for better survival, whereas patients with HLA-A2, -B7, or -B18 had a trend for shorter survival. We conclude that response to IFN-A in patients with CML may be associated with the HLA phenotype. However, a much larger population would be required to determine if the impact of HLA phenotype on survival is independent of other clinical prognostic features. These findings could be relevant for the understanding of immune mechanisms of control of CML and possibly the design of immune therapy for this disease.

AB - Twenty to 25% of patients with chronic myelogenous leukemia (CML) treated with interferon-alpha (IFN-A) achieve a complete cytogenetic response (CCR). However, cells bearing rearrangement of BCR/ABL can still be detected many years after achieving a CCR despite the absence of clinical evidence of active disease. It has been suggested that the disease is kept in a dormant state by immune mechanisms. How this is achieved is not known, but it has been speculated that p210(BCR/ABL) might be presented by malignant cells through HLA molecules, thus making them the target for specific immune cell killing. Because specific peptides will be expressed in association with certain HLA molecules, different HLA phenotypes could be associated with different response rates to IFN-A. The response to IFN-A-based therapies in 239 patients with chronic phase CML was analyzed according to their HLA phenotype. One hundred and ninety-four (81%) achieved complete hematologic response, 142 (59%) had a cytogenetic response which was major (MCR) in 93 patients (39%): complete (CCR) in 71 (30%) and partial (PCR) in 22 (9%). Patients with an HLA-B27 phenotype had the best response rate to IFN-A: 10 of 14 (71%) had an MCR, including eight (57%) with a CCR (P = 0.02). Patients with HLA-B35, -A3, and -A31 also showed a trend towards a higher response rate, whereas patients with HLA-B18 had the lowest response rate (MCR 17%). Patients with HLA-B27 and those with HLA-A31 showed a trend for better survival, whereas patients with HLA-A2, -B7, or -B18 had a trend for shorter survival. We conclude that response to IFN-A in patients with CML may be associated with the HLA phenotype. However, a much larger population would be required to determine if the impact of HLA phenotype on survival is independent of other clinical prognostic features. These findings could be relevant for the understanding of immune mechanisms of control of CML and possibly the design of immune therapy for this disease.

KW - Chronic myelogenous leukemia

KW - HLA

KW - Interferon-alpha

UR - http://www.scopus.com/inward/record.url?scp=0031981132&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031981132&partnerID=8YFLogxK

U2 - 10.1038/sj.leu.2400965

DO - 10.1038/sj.leu.2400965

M3 - Article

C2 - 9557601

AN - SCOPUS:0031981132

VL - 12

SP - 455

EP - 462

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 4

ER -