An observational study in Hemophagocytic Lymphohistiocytosis (HLH), sponsored by Peking University People's Hospital. Recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-29.
Sponsored by Peking University People's Hospital · Observational
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.
This multicenter ambispective longitudinal observational cohort study will characterize de novo hemophagocytic lymphohistiocytosis (HLH) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and develop and independently validate a dynamic model for HLH occurrence within the next seven days. Eligible participants are adults aged 18 years or older at their first allo-HSCT. Patients with HLH diagnosed before transplantation or transplantation performed primarily for HLH are excluded.
The retrospective component includes first allo-HSCT performed from January 1, 2014, through the day before prospective study activation at each center. Records available before activation will be reviewed. A stratified case-cohort design will be used: a 15% random subcohort will be selected within center and transplant-year strata, and all eligible HLH cases in the source cohort will be included in the detailed analysis. Patients belonging to both the random subcohort and the HLH case set will be counted once. Basic transplant and outcome information will be collected for the source cohort.
The prospective component will consecutively enroll eligible patients after ethics approval and site activation through December 31, 2029. Written informed consent will be obtained before transplantation, and participants will enter the transplant cohort after the procedure is completed. Additional research follow-up of retrospectively identified patients will require written informed consent. The planned combined source cohort comprises approximately 20,000 recipients, including approximately 400 expected HLH cases.
Data collection includes underlying disease and disease status, comorbidities, donor and transplant characteristics, conditioning, graft-versus-host disease prophylaxis, engraftment, infections, viral reactivation, post-transplant lymphoproliferative disease, organ dysfunction, and treatments. Longitudinal routine laboratory data include blood counts, ferritin, C-reactive protein, fibrinogen, triglycerides, D-dimer, lactate dehydrogenase, albumin, and liver and kidney function. Cytokines, soluble CD25, and natural killer cell function results will be recorded when obtained during routine care. Sampling times, result availability times, units, and reference ranges will be retained.
The primary clinical outcome is the first de novo HLH episode within 365 days after allo-HSCT. An episode must meet at least five of the eight HLH-2004 criteria during the same clinical episode and be confirmed by the adjudication group. Two investigators will independently review potential cases, with a third investigator resolving disagreement. The onset date is the earliest date on which the study definition is fulfilled. Dates of first clinical suspicion, clinical diagnosis, and HLH-directed treatment initiation will also be recorded. Clinically diagnosed episodes not meeting the primary definition will be recorded separately for supplementary analyses. Adjudicators will not have access to new-model predictions. Death and second allogeneic transplantation before HLH will be treated as competing events.
At evaluable assessment times from day 1 through day 358 after transplantation, information already available at that time will be used to predict first HLH onset within the subsequent seven days. Model evaluation will use assessments obtained before HLH onset and before initiation of HLH-directed treatment. Models and thresholds will be fixed before independent-center and prospective validation. Prospective predictions will be recorded for research and will not be provided to treating teams as treatment decision prompts.
Follow-up will continue through one year after transplantation. Clinical and outcome information will be reviewed monthly during the first six months and at months 9 and 12; routine inpatient data will be collected longitudinally. For participants who develop HLH during the first year, additional assessments will be recorded on days 7, 14, 28, 60, and 90 after HLH onset. Follow-up will use hospital and outpatient records, telephone, online or video contact, or in-person visits. Patients developing HLH late in the first year may be followed for up to approximately 15 months after transplantation.
Analyses will account for case-cohort sampling, competing events, center, and transplant period. Dynamic landmark models, penalized regression, and gradient boosting will be evaluated. Inflammatory characteristics will be examined using representative subcohort data and compared with clinical and simplified models. Performance will be assessed using discrimination, calibration, Brier scores, decision curves, case detection, positive predictive value, warning lead time, and false-alert frequency. Secondary analyses will describe HLH triggers, organ support, treatment patterns, recorded early treatment response, and survival.
The study does not assign treatment or require additional blood sampling, laboratory tests, or biospecimen retention. Historical records will be used under the applicable ethics-approved consent or waiver procedures; prospective participants will provide written informed consent. Each site will retain its identity linkage file. The coordinating database will receive coded data without direct personal identifiers, and results will be reported in aggregate.
111 studies on the registry are indexed under Lymphohistiocytosis, Hemophagocytic; 41 are open to participants now.
This study's planned enrollment of 10,000 is above the median of 114 across 34 observational studies indexed under Lymphohistiocytosis, Hemophagocytic.
Browse Lymphohistiocytosis, Hemophagocytic studies →Peking University People's Hospital is the lead sponsor of 609 studies on the registry; 247 are open to participants now.
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Adults aged 18 years or older undergoing their first allogeneic hematopoietic stem cell transplantation at participating centers in China. The source population includes recipients who develop post-transplant HLH and those who do not. The retrospective component includes eligible transplantations from January 1, 2014, to the day before prospective study activation at each center. The prospective component consecutively enrolls eligible transplant recipients after site activation through December 31, 2029. A center- and transplant-year-stratified 15% random subcohort and all HLH cases are selected for detailed retrospective analysis.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
First allogeneic hematopoietic stem cell transplantation performed at a participating center within the study period.
Verifiable transplantation date and basic clinical information. Written from the participant or legally authorized representative for prospective participation. Retrospective records are used under the applicable ethics-approved consent or waiver procedures.
Exclusion Criteria:
HLH diagnosed before transplantation, or transplantation performed primarily for HLH.
Previous allogeneic hematopoietic stem cell transplantation. Patient identity, transplantation date, or key outcome information cannot be verified.
Explicit refusal to participate or to permit the use of clinical information for this study.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients whose first visit to our institution and the termination of follow-up both occurred before the opening of this study will contribute to the retrospective cohort.
Patients whose first visit to our institution occur after the opening of this study will contribute to the prospective cohort.
Patients whose first visit to our institution occurred before the opening of this study and whose follow-up will terminate after the opening of this study will contribute to the ambispective cohort.
Cumulative Incidence of First De Novo HLH Within 365 Days After Transplantation
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.
Time frame: From transplantation through day 365.
Discrimination of the 7-Day HLH Risk Prediction Model
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.
Time frame: At evaluable assessments on days 1 to 358 after transplantation, with HLH occurrence evaluated over the subsequent 7 days, through day 365.
Calibration of Predicted 7-Day HLH Risk
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.
Time frame: At evaluable assessments on days 1 to 358 after transplantation, with HLH occurrence evaluated over the subsequent 7 days, through day 365.
Positive Predictive Value of 7-Day HLH Alerts
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.
Time frame: At evaluable assessments on days 1 to 358 after transplantation, with HLH occurrence evaluated over the subsequent 7 days, through day 365.
Case Detection Rate for Incident HLH
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.
Time frame: At evaluable assessments on days 1 to 358 after transplantation, with HLH occurrence evaluated over the subsequent 7 days, through day 365.
Cumulative Incidence of HLH Within 100 Days After Transplantation
Cumulative incidence of first adjudicated de novo HLH, using the same definition as the primary clinical outcome. Death and second allogeneic transplantation before HLH are competing events.
Time frame: From transplantation through day 100.
All-Cause Mortality Within 28 Days After HLH Onset
Probability of death from any cause within 28 days after adjudicated HLH onset among participants who develop HLH. Follow-up time starts on the HLH onset date.
Time frame: From HLH onset through day 28 after onset.
All-Cause Mortality Within 60 Days After HLH Onset
Probability of death from any cause within 60 days after adjudicated HLH onset among participants who develop HLH. Follow-up time starts on the HLH onset date.
Time frame: From HLH onset through day 60 after onset.
All-Cause Mortality Within 90 Days After HLH Onset
Probability of death from any cause within 90 days after adjudicated HLH onset among participants who develop HLH. Follow-up time starts on the HLH onset date.
Time frame: From HLH onset through day 90 after onset.
Overall Survival at One Year After Transplantation
Probability of survival one year after first allogeneic hematopoietic stem cell transplantation. Death from any cause is the event, and follow-up time starts on the transplantation date.
Time frame: From transplantation through day 365.
Plan to share: No — There is no current plan to share individual participant data with external researchers. The study involves multicenter clinical records, and access to patient-level data is subject to applicable ethical approvals, institutional policies, and data-use agreements.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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