Hemophagocytic Lymphohistiocytosis After Allogeneic Stem Cell Transplantation

Condition(s) studied

Study summary

Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory complication that can occur after allogeneic hematopoietic stem cell transplantation. Its signs can overlap with those of infection and other transplant complications, making early recognition difficult. This study will examine whether changes in routine blood tests and clinical information can help identify patients who may develop HLH during the following seven days.

The study will combine a review of existing medical records with prospective follow-up at participating hospitals in China. Approximately 20,000 adults undergoing their first allogeneic transplantation will be included, with approximately 400 post-transplant HLH cases expected. Historical records will be used to develop the prediction model. Data from independent centers and prospectively enrolled patients will be used to validate the model.

Participants will be followed for one year after transplantation. Those who develop HLH during that year will also be followed for 90 days after HLH onset. The study will describe HLH occurrence, associated factors, treatments, and survival. All tests and treatments will remain part of routine care. No additional research samples or laboratory tests will be required, and model predictions will not be used to guide treatment.

Eligibility

Primary outcome measure(s)

• Cumulative Incidence of First De Novo HLH Within 365 Days After Transplantation — From transplantation through day 365.
  Cumulative incidence of the first adjudicated de novo HLH episode after first allogeneic hematopoietic stem cell transplantation. HLH requires at least five of the eight HLH-2004 criteria within the same clinical episode and confirmation by the adjudication group. The onset date is the first date the study definition is met. Death and second allogeneic transplantation before HLH are competing events.
• Discrimination of the 7-Day HLH Risk Prediction Model — At evaluable assessments on days 1 to 358 after transplantation, with HLH occurrence evaluated over the subsequent 7 days, through day 365.
  Time-dependent area under the receiver operating characteristic curve for predicting first HLH onset within the next seven days, evaluated separately in independent-center and prospective validation cohorts. Values range from 0 to 1, with higher values indicating better discrimination. Estimates account for the sampling design and follow-up.
• Calibration of Predicted 7-Day HLH Risk — At evaluable assessments on days 1 to 358 after transplantation, with HLH occurrence evaluated over the subsequent 7 days, through day 365.
  Agreement between predicted seven-day probabilities and observed seven-day HLH occurrence, evaluated using calibration curves in independent-center and prospective validation cohorts. Observed occurrence estimates account for the sampling design, follow-up, and competing events.
• Positive Predictive Value of 7-Day HLH Alerts — At evaluable assessments on days 1 to 358 after transplantation, with HLH occurrence evaluated over the subsequent 7 days, through day 365.
  Percentage of evaluable model-positive assessments followed by adjudicated first HLH onset within the next seven days. A positive assessment is defined using the prediction threshold fixed before validation. Estimates are adjusted for the sampling design and follow-up where applicable.
• Case Detection Rate for Incident HLH — At evaluable assessments on days 1 to 358 after transplantation, with HLH occurrence evaluated over the subsequent 7 days, through day 365.
  Percentage of adjudicated incident HLH cases with at least one model-positive assessment during the seven days before onset, among cases with an eligible pre-onset model assessment. The prediction threshold is fixed before validation. Estimates are adjusted for the sampling design and follow-up where applicable.

Trial sites (1)

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