Time-dependent effects of clinical predictors in unrelated hematopoietic stem cell transplantation

Haematologica. 2016 Feb;101(2):241-7. doi: 10.3324/haematol.2015.130401. Epub 2015 Nov 26.

Abstract

Hematopoietic stem cell transplantation is a multifactorial process. Some of the predictors exhibit time-dependent effects. We present a systematic analysis and description of selected clinical predictors influencing outcome in a time-dependent manner based on an analysis of registry data from the German Registry for Stem Cell Transplantation. A total of 14,951 patients with acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome and non-Hodgkin lymphoma transplanted with peripheral blood stem cells or bone marrow grafts were included. Multivariate Cox regression models were tested for time-dependent effects within each diagnosis group. Predictors not satisfying the proportional hazards assumption were modeled in a time-dependent manner, extending the Cox regression models. Similar patterns occurred in all diagnosis groups. Patients with a poor Karnofsky performance score (<80) had a high risk for early mortality until day 139 following transplantation (HR 2.42, CI: 2.19-2.68; P<0.001) compared to patients with a good Karnofsky performance score (80-100). Afterwards the risk reduced to HR 1.43, CI: 1.25-1.63; P<0.001. A lower mortality risk was found for patients after conditioning treatment with reduced intensity until day 120 post transplant (HR: 0.81 CI: 0.75-0.88; P<0.001). After this, a slightly higher risk could be shown for these patients. Similarly, patients who had received a PBSC graft exhibited a significantly lower mortality risk until day 388 post transplantation (HR 0.79, CI: 0.73-0.85; P<0.001), reversing to a significantly higher risk afterwards (HR 1.23, CI: 1.08-1.40; P=0.002). Integrating time dependency in regression models allows a more accurate description and quantification of clinical predictors to be made, which may help in risk assessment and patient counseling.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Female
  • Germany
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy
  • Lymphoma, Non-Hodgkin / diagnosis*
  • Lymphoma, Non-Hodgkin / mortality
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoma, Non-Hodgkin / therapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / diagnosis*
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / pathology
  • Myelodysplastic Syndromes / therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis
  • Proportional Hazards Models
  • Registries*
  • Retrospective Studies
  • Risk
  • Time Factors
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Unrelated Donors

Substances

  • Antineoplastic Agents