Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma.
BACKGROUND
Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT.


METHODS
In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic score was then validated in an independent clinical sample (part II).


RESULTS
In part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [<partial remission by computed tomography (CT)] as significant and non-redundant RFs for PFS. A risk score composed of these equally weighed RFs was significantly prognostic for PFS (HR = 1.67 for each additional RF; P < 0.0001). Validation in an independent sample of 389 patients treated in different clinical settings with evaluation of response to salvage therapy by functional imaging instead of CT confirmed the excellent discrimination of risk groups and significant prognostication of PFS and overall survival (OS) after ASCT (HR = 1.70 and HR = 1.63, respectively; P < 0.0001).


CONCLUSIONS
Based on this large study (n = 1045), precise and valid risk prognostication in HL patients undergoing ASCT can be achieved with five easily available clinical RFs. The proposed prognostic score hence allows reliable stratification of patients for innovative therapeutic approaches in clinical practice and future trials.
GHSG HD10 NCT00265018, HD11 NCT00264953, HD12 NCT00265031, HD13 ISRCTN63474366, HD14 ISRCTN04761296, HD15 ISRCTN32443041 and HDR2 NCT00025636.
Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany.
P J
PJ
Bröckelmann
Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany.
H
H
Müller
Department of Hematology and Lymphoma Study Association (LYSA), Hopital Le Bocage, CHU Dijon, Dijon, France.
O
O
Casasnovas
Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark.
M
M
Hutchings
Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany.
B
B
von Tresckow
Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark.
M
M
Jürgens
Memorial Sloan Kettering Cancer Center (MSKCC), New York City, USA.
S J
SJ
McCall
Department of Hematology, Unité GRITA, Université de Lille 2, Hopital Claude Huriez, Lille, France.
F
F
Morschhauser
Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany.
M
M
Fuchs
Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany.
P
P
Borchmann
Memorial Sloan Kettering Cancer Center (MSKCC), New York City, USA.
C H
CH
Moskowitz
Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany.
A
A
Engert
D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis
ASCT; Hodgkin lymphoma; prognosis; relapse; risk factors; score