Malignancy-associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes

Gevorg N. Tamamyan, Hagop M. Kantarjian, Jing Ning, Preetesh Jain, Koji Sasaki, Kenneth L. McClain, Carl E. Allen, Sherry A. Pierce, Jorge E. Cortes, Farhad Ravandi, Marina Y. Konopleva, Guillermo Garcia-Manero, Christopher B. Benton, Dai Chihara, Michael E. Rytting, Sa Wang, Waleed Abdelall, Sergej N. Konoplev, Naval G. Daver

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Malignancy-associated hemophagocytic lymphohistiocytosis (HLH) in adults is a highly lethal disorder. Knowledge gaps have resulted in under diagnosis or delayed diagnosis. METHODS: The University of Texas MD Anderson Cancer Center pathology database (1991-2014) was retrospectively interrogated for the keywords “hemophagocytosis” and/or “lymphohistiocytosis.” Seventy-seven adult patients were identified. All had an underlying malignancy. Sixteen patients who had insufficient documentation were excluded. RESULTS: The majority of patients who had pathologic evidence of hemophagocytosis/lymphohistiocytosis had an incomplete workup to confirm or refute HLH using the 2004 HLH criteria (HLH-2004; n = 8 variables), which is a common problem in adult HLH. Only 13 of 61 patients (21%) met the HLH-2004 diagnostic criteria based on available retrospective data. To identify potentially missed cases of HLH, the published literature was reviewed, and selected additional variables known to be associated with adult HLH were selected, resulting in extended diagnostic criteria of 18 variables. Thirty-five patients met the extended criteria, and 33 had follow-up data available. The median overall survival of the 13 patients who met both the extended criteria and the HLH-2004 criteria was similar to that of the 20 patients who met the extended criteria but NOT the HLH-2004 criteria (1.43 vs 1.76 months, respectively; P =.34) indicating a similar underlying, aggressive, systemic process. Twenty-six patients did not meet either criteria, and 17 had follow-up data available. The median overall survival of the 17 patients who had pathologic hemophagocytosis or lymphohistiocytosis but met neither criteria was significantly superior to the survival of those who met both the extended criteria and the HLH-2004 criteria and those who met the extended criteria but not the HLH-2004 criteria (17.27 vs 1.43 vs 1.76, respectively; P =.002). CONCLUSIONS: The addition of diagnostic laboratory variables that are more easily and rapidly available in smaller institutions and primary care settings than the HLH-2004 variables may be a good surrogate to raise early suspicion of malignancy-associated HLH. Prospective validation is warranted. Cancer 2016.

Original languageEnglish (US)
Pages (from-to)2857-2866
Number of pages10
JournalCancer
Volume122
Issue number18
DOIs
StatePublished - Sep 15 2016
Externally publishedYes

Fingerprint

Hemophagocytic Lymphohistiocytosis
Neoplasms
Survival
Delayed Diagnosis
Documentation

Keywords

  • adults
  • ferritin
  • hemophagocytosis
  • lymphohistiocytosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tamamyan, G. N., Kantarjian, H. M., Ning, J., Jain, P., Sasaki, K., McClain, K. L., ... Daver, N. G. (2016). Malignancy-associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes. Cancer, 122(18), 2857-2866. https://doi.org/10.1002/cncr.30084

Malignancy-associated hemophagocytic lymphohistiocytosis in adults : Relation to hemophagocytosis, characteristics, and outcomes. / Tamamyan, Gevorg N.; Kantarjian, Hagop M.; Ning, Jing; Jain, Preetesh; Sasaki, Koji; McClain, Kenneth L.; Allen, Carl E.; Pierce, Sherry A.; Cortes, Jorge E.; Ravandi, Farhad; Konopleva, Marina Y.; Garcia-Manero, Guillermo; Benton, Christopher B.; Chihara, Dai; Rytting, Michael E.; Wang, Sa; Abdelall, Waleed; Konoplev, Sergej N.; Daver, Naval G.

In: Cancer, Vol. 122, No. 18, 15.09.2016, p. 2857-2866.

Research output: Contribution to journalArticle

Tamamyan, GN, Kantarjian, HM, Ning, J, Jain, P, Sasaki, K, McClain, KL, Allen, CE, Pierce, SA, Cortes, JE, Ravandi, F, Konopleva, MY, Garcia-Manero, G, Benton, CB, Chihara, D, Rytting, ME, Wang, S, Abdelall, W, Konoplev, SN & Daver, NG 2016, 'Malignancy-associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes', Cancer, vol. 122, no. 18, pp. 2857-2866. https://doi.org/10.1002/cncr.30084
Tamamyan, Gevorg N. ; Kantarjian, Hagop M. ; Ning, Jing ; Jain, Preetesh ; Sasaki, Koji ; McClain, Kenneth L. ; Allen, Carl E. ; Pierce, Sherry A. ; Cortes, Jorge E. ; Ravandi, Farhad ; Konopleva, Marina Y. ; Garcia-Manero, Guillermo ; Benton, Christopher B. ; Chihara, Dai ; Rytting, Michael E. ; Wang, Sa ; Abdelall, Waleed ; Konoplev, Sergej N. ; Daver, Naval G. / Malignancy-associated hemophagocytic lymphohistiocytosis in adults : Relation to hemophagocytosis, characteristics, and outcomes. In: Cancer. 2016 ; Vol. 122, No. 18. pp. 2857-2866.
@article{18410ad6d0fe43eda426e3aeacc49b13,
title = "Malignancy-associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes",
abstract = "BACKGROUND: Malignancy-associated hemophagocytic lymphohistiocytosis (HLH) in adults is a highly lethal disorder. Knowledge gaps have resulted in under diagnosis or delayed diagnosis. METHODS: The University of Texas MD Anderson Cancer Center pathology database (1991-2014) was retrospectively interrogated for the keywords “hemophagocytosis” and/or “lymphohistiocytosis.” Seventy-seven adult patients were identified. All had an underlying malignancy. Sixteen patients who had insufficient documentation were excluded. RESULTS: The majority of patients who had pathologic evidence of hemophagocytosis/lymphohistiocytosis had an incomplete workup to confirm or refute HLH using the 2004 HLH criteria (HLH-2004; n = 8 variables), which is a common problem in adult HLH. Only 13 of 61 patients (21{\%}) met the HLH-2004 diagnostic criteria based on available retrospective data. To identify potentially missed cases of HLH, the published literature was reviewed, and selected additional variables known to be associated with adult HLH were selected, resulting in extended diagnostic criteria of 18 variables. Thirty-five patients met the extended criteria, and 33 had follow-up data available. The median overall survival of the 13 patients who met both the extended criteria and the HLH-2004 criteria was similar to that of the 20 patients who met the extended criteria but NOT the HLH-2004 criteria (1.43 vs 1.76 months, respectively; P =.34) indicating a similar underlying, aggressive, systemic process. Twenty-six patients did not meet either criteria, and 17 had follow-up data available. The median overall survival of the 17 patients who had pathologic hemophagocytosis or lymphohistiocytosis but met neither criteria was significantly superior to the survival of those who met both the extended criteria and the HLH-2004 criteria and those who met the extended criteria but not the HLH-2004 criteria (17.27 vs 1.43 vs 1.76, respectively; P =.002). CONCLUSIONS: The addition of diagnostic laboratory variables that are more easily and rapidly available in smaller institutions and primary care settings than the HLH-2004 variables may be a good surrogate to raise early suspicion of malignancy-associated HLH. Prospective validation is warranted. Cancer 2016.",
keywords = "adults, ferritin, hemophagocytosis, lymphohistiocytosis",
author = "Tamamyan, {Gevorg N.} and Kantarjian, {Hagop M.} and Jing Ning and Preetesh Jain and Koji Sasaki and McClain, {Kenneth L.} and Allen, {Carl E.} and Pierce, {Sherry A.} and Cortes, {Jorge E.} and Farhad Ravandi and Konopleva, {Marina Y.} and Guillermo Garcia-Manero and Benton, {Christopher B.} and Dai Chihara and Rytting, {Michael E.} and Sa Wang and Waleed Abdelall and Konoplev, {Sergej N.} and Daver, {Naval G.}",
year = "2016",
month = "9",
day = "15",
doi = "10.1002/cncr.30084",
language = "English (US)",
volume = "122",
pages = "2857--2866",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "18",

}

TY - JOUR

T1 - Malignancy-associated hemophagocytic lymphohistiocytosis in adults

T2 - Relation to hemophagocytosis, characteristics, and outcomes

AU - Tamamyan, Gevorg N.

AU - Kantarjian, Hagop M.

AU - Ning, Jing

AU - Jain, Preetesh

AU - Sasaki, Koji

AU - McClain, Kenneth L.

AU - Allen, Carl E.

AU - Pierce, Sherry A.

AU - Cortes, Jorge E.

AU - Ravandi, Farhad

AU - Konopleva, Marina Y.

AU - Garcia-Manero, Guillermo

AU - Benton, Christopher B.

AU - Chihara, Dai

AU - Rytting, Michael E.

AU - Wang, Sa

AU - Abdelall, Waleed

AU - Konoplev, Sergej N.

AU - Daver, Naval G.

PY - 2016/9/15

Y1 - 2016/9/15

N2 - BACKGROUND: Malignancy-associated hemophagocytic lymphohistiocytosis (HLH) in adults is a highly lethal disorder. Knowledge gaps have resulted in under diagnosis or delayed diagnosis. METHODS: The University of Texas MD Anderson Cancer Center pathology database (1991-2014) was retrospectively interrogated for the keywords “hemophagocytosis” and/or “lymphohistiocytosis.” Seventy-seven adult patients were identified. All had an underlying malignancy. Sixteen patients who had insufficient documentation were excluded. RESULTS: The majority of patients who had pathologic evidence of hemophagocytosis/lymphohistiocytosis had an incomplete workup to confirm or refute HLH using the 2004 HLH criteria (HLH-2004; n = 8 variables), which is a common problem in adult HLH. Only 13 of 61 patients (21%) met the HLH-2004 diagnostic criteria based on available retrospective data. To identify potentially missed cases of HLH, the published literature was reviewed, and selected additional variables known to be associated with adult HLH were selected, resulting in extended diagnostic criteria of 18 variables. Thirty-five patients met the extended criteria, and 33 had follow-up data available. The median overall survival of the 13 patients who met both the extended criteria and the HLH-2004 criteria was similar to that of the 20 patients who met the extended criteria but NOT the HLH-2004 criteria (1.43 vs 1.76 months, respectively; P =.34) indicating a similar underlying, aggressive, systemic process. Twenty-six patients did not meet either criteria, and 17 had follow-up data available. The median overall survival of the 17 patients who had pathologic hemophagocytosis or lymphohistiocytosis but met neither criteria was significantly superior to the survival of those who met both the extended criteria and the HLH-2004 criteria and those who met the extended criteria but not the HLH-2004 criteria (17.27 vs 1.43 vs 1.76, respectively; P =.002). CONCLUSIONS: The addition of diagnostic laboratory variables that are more easily and rapidly available in smaller institutions and primary care settings than the HLH-2004 variables may be a good surrogate to raise early suspicion of malignancy-associated HLH. Prospective validation is warranted. Cancer 2016.

AB - BACKGROUND: Malignancy-associated hemophagocytic lymphohistiocytosis (HLH) in adults is a highly lethal disorder. Knowledge gaps have resulted in under diagnosis or delayed diagnosis. METHODS: The University of Texas MD Anderson Cancer Center pathology database (1991-2014) was retrospectively interrogated for the keywords “hemophagocytosis” and/or “lymphohistiocytosis.” Seventy-seven adult patients were identified. All had an underlying malignancy. Sixteen patients who had insufficient documentation were excluded. RESULTS: The majority of patients who had pathologic evidence of hemophagocytosis/lymphohistiocytosis had an incomplete workup to confirm or refute HLH using the 2004 HLH criteria (HLH-2004; n = 8 variables), which is a common problem in adult HLH. Only 13 of 61 patients (21%) met the HLH-2004 diagnostic criteria based on available retrospective data. To identify potentially missed cases of HLH, the published literature was reviewed, and selected additional variables known to be associated with adult HLH were selected, resulting in extended diagnostic criteria of 18 variables. Thirty-five patients met the extended criteria, and 33 had follow-up data available. The median overall survival of the 13 patients who met both the extended criteria and the HLH-2004 criteria was similar to that of the 20 patients who met the extended criteria but NOT the HLH-2004 criteria (1.43 vs 1.76 months, respectively; P =.34) indicating a similar underlying, aggressive, systemic process. Twenty-six patients did not meet either criteria, and 17 had follow-up data available. The median overall survival of the 17 patients who had pathologic hemophagocytosis or lymphohistiocytosis but met neither criteria was significantly superior to the survival of those who met both the extended criteria and the HLH-2004 criteria and those who met the extended criteria but not the HLH-2004 criteria (17.27 vs 1.43 vs 1.76, respectively; P =.002). CONCLUSIONS: The addition of diagnostic laboratory variables that are more easily and rapidly available in smaller institutions and primary care settings than the HLH-2004 variables may be a good surrogate to raise early suspicion of malignancy-associated HLH. Prospective validation is warranted. Cancer 2016.

KW - adults

KW - ferritin

KW - hemophagocytosis

KW - lymphohistiocytosis

UR - http://www.scopus.com/inward/record.url?scp=84985893581&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84985893581&partnerID=8YFLogxK

U2 - 10.1002/cncr.30084

DO - 10.1002/cncr.30084

M3 - Article

C2 - 27244347

AN - SCOPUS:84985893581

VL - 122

SP - 2857

EP - 2866

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 18

ER -