Combined Haploidentical-Cord Blood Transplantation for Adults and Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combined Haploidentical-Cord Blood Transplantation for Adults and Children (NCT00943800), a non-randomized na study. The primary outcome is Percentage of Participants With Neutrophil Engraftment.

2. Clinical Question

The registry also identifies acute and chronic graft-versus-host disease (GVHD) and survival as secondary outcomes. It describes assessment of acute GVHD of Grade II-IV and chronic GVHD, along with survival at 2 years and 5 years. Numerical results for these secondary outcomes are not reported in the registry record.

The clinical question is therefore descriptive: what engraftment and safety outcomes occurred among participants treated in this single-group study? Without a randomized comparison, the record cannot establish how outcomes would have differed under another treatment strategy. It also does not report enough detail to determine how participants were distributed across the listed treatment regimens or risk categories.

3. Trial Design

This was a completed, non-randomized, single-group study registered as “Combined Haploidentical-Cord Blood Transplantation for Adults and Children.” The registry lists an enrollment of 87 and identifies the University of Chicago as sponsor. The study began on 2006-10-09, and primary completion is recorded as 2018-09. The phase is listed as NA.

The intervention of interest was combined haploidentical-cord blood transplantation. The registry lists stem cell transplantation and stem cell collections, alongside drug regimens containing fludarabine, melphalan, rabbit antithymocyte globulin, thiotepa, total body irradiation, busulfan, and antithymocyte globulin. These entries describe interventions recorded for the study; they do not establish that every participant received every listed component.

Risk-based arm descriptions are included in the registry. The description for “Good Risks patients” says that these were patients transplanted in remission. The descriptions for the high-risk groups, including those eligible and not eligible for radiation, are blank. The record does not explain how the listed regimens were assigned, whether treatment changed over time, or how risk groups corresponded to the intervention entries.

Masking is listed as none. As a single-group, non-randomized study, this design can describe outcomes among treated participants but does not supply a randomized control comparison. Differences between patient groups or treatment approaches, if any, would not necessarily represent causal treatment effects. The registry record does not report a statistical analysis plan, sample-size justification, or details of any interim analyses.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Neutrophil Engraftment, measured over Transplant (Day 0) through Day +28.

The primary outcome is titled “Percentage of Participants With Neutrophil Engraftment.” Its listed timeframe is from transplant (Day 0) through Day +28. The accompanying description, however, says that cumulative incidence of neutrophil graft failure by day 28 was reported. This distinction matters: the title emphasizes successful engraftment, while the description emphasizes failure to engraft. The registry record does not report a numerical estimate that would resolve how the posted primary result was expressed.

The description defines failure to engraft as a lack of evidence of hematopoietic recovery by day +35, with specified blood-count thresholds and confirmation by a biopsy showing low marrow cellularity. It also describes graft failure after initial myeloid engraftment followed by a sustained drop in the absolute neutrophil count, independent of listed causes. Death before neutrophil engraftment is treated as a competing risk in the described assessment.

Engraftment is relevant because it indicates recovery of blood-cell production after transplantation. The endpoint is used to assess whether donor-derived hematopoiesis becomes established, while a graft-failure measure captures failure or loss of that recovery. In general, a competing risk is an event that prevents the event of interest from subsequently being observed; accounting for it can make an incidence estimate more appropriate than treating such an event as ordinary follow-up loss. The registry record does not report the primary endpoint estimate or its confidence interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It describes the primary endpoint, notes a 95% Confidence Interval as the dispersion measure, and states that death before neutrophil engraftment was treated as a competing risk. It does not report a numerical primary estimate, confidence interval bounds, or the analysis method used to obtain them. The explanations below describe general statistical concepts; they do not establish which unreported methods were used in this study.

What does a confidence interval communicate?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical procedure. A narrow interval indicates greater precision than a wide interval, while an interval’s location indicates the range of values compatible with the estimate and method. It is not a guarantee that the true value lies within the interval, nor does it correct for bias from study design, outcome measurement, or missing information. The registry identifies a 95% confidence interval for the primary endpoint but does not report its bounds, so the precision of the estimate cannot be assessed.

Why does competing risk matter for engraftment?

In general, a competing event prevents the event of interest from occurring or being observed afterward. Death before engraftment is the competing event named in this endpoint description. If deaths were instead treated as if participants remained able to engraft, an incidence estimate could misrepresent the probability of observing engraftment or graft failure in the presence of death. A cumulative-incidence approach can account for competing events, but the registry’s wording alone does not establish the estimator or model used. It reports no numerical estimate or method details.

How should an event percentage be read?

For an outcome expressed as a percentage of participants with an event, the numerator is the number of participants meeting the outcome definition and the denominator is the relevant group under analysis. In general, interpretation depends on both: the percentage alone does not reveal how many observations contributed or how uncertainty was estimated. The registry’s primary outcome title uses a percentage, but it does not post the observed primary percentage or its event count. The enrollment figure should not be assumed to be the analysis denominator for every outcome.

What can be learned from a single-group design?

A single-group study can describe outcomes observed among participants receiving the study intervention. Without a concurrent randomized comparator, it cannot separate treatment effects from other explanations such as differences in participant characteristics, disease status, clinical care, or follow-up. Non-randomized comparisons, if made among groups, may also reflect why participants entered those groups. The registry’s risk-group descriptions are incomplete, and the record does not explain how interventions were allocated. Thus, the design should be read as observational evidence about outcomes in the recorded treatment setting, not as a randomized estimate of comparative effects.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, not the original trial design. The stated illustration assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the stated planning quantity is the total number of events using the Schoenfeld approach; for other outcomes, it is participants per arm. These are planning conventions, not observed results or observed power.

The registry record does not report the illustration’s resulting sample-size values, an observed effect for use in that calculation, or a sample-size justification for the actual study. In addition, a two-arm planning illustration does not match the registered single-group design. It therefore should not be interpreted as evidence that the study was designed or powered for a particular comparison. No conclusion about whether the enrolled study was adequately sized can be drawn from the assumptions alone.

What is not reported about the analyses?

The registry record does not report a statistical analysis plan, model specifications, handling of censoring, covariate adjustment, or analysis populations. It does not describe methods for the secondary GVHD or survival outcomes. In general, these details affect the estimand, assumptions, and precision of an analysis. Without them, the outcome definitions cannot be translated into a reproducible account of the statistical analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment Group")
n      <- c(87)
events <- c(74)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment Group  87  74  85.1  75.8  91.8  76.1  91.1  76.1  91.0

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and secondary outcomes, but it does not report a statistical plan for controlling multiplicity across those outcomes. When a study evaluates several outcomes, the chance of obtaining an apparently notable result can increase if each is tested separately without a prespecified approach. This is a general statistical concern; the registry record does not state whether any adjustment, hierarchy, or other multiplicity strategy was used.

Numerical results for the primary endpoint and secondary outcomes are not reported in the registry record. The record does not provide outcome-specific denominators, missing-data counts, reasons for missingness, or rules for excluding participants from each analysis. It also does not describe whether participants were analyzed according to the original treatment assignment or another analysis population. Therefore, the extent and handling of missing data, and the relationship between enrollment and analyzed populations, are not reported in the registry record.

In general, missing observations can affect an estimate if the probability of being observed is related to the outcome. Different approaches to missing data rely on different assumptions, so an analysis method should be reported before its implications can be assessed. No such method is described in this registry record. The record also does not report interim analyses, stopping rules, or procedures for selecting which outcomes to emphasize. These omissions limit assessment of analysis transparency and the risk of selective reporting.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: sepsis (12.6%), respiratory failure (4.6%), epstein-barr virus infection (3.4%), hypoxia (3.4%), abdominal infection (2.3%).

The registry’s adverse-event entry lists a treatment group with 87 participants at risk for serious adverse events and 24 affected. For other adverse events, it lists 87 at risk and 0 affected. It records 18 deaths. These are the values recorded for the group; the registry record does not specify the safety reporting window or explain how deaths relate to the adverse-event categories.

The listed serious adverse-event terms include sepsis at 12.6%, respiratory failure at 4.6%, Epstein-barr virus infection at 3.4%, and hypoxia at 3.4%. Abdominal infection and lung infection are each listed at 2.3%. These percentages should be read as recorded event-term figures, not as evidence that the terms are mutually exclusive or that each represents a separate participant. The record does not give the corresponding term counts or explain the denominator used for each percentage.

Adverse-event reporting describes events observed and recorded during a study; it does not by itself establish that the intervention caused them. The record does not report attribution details, event timing, severity beyond the serious-event classification, or a comparative safety group. The counts and terms therefore provide limited descriptive safety information, not a controlled estimate of treatment-related risk.

13. What the Result Does, and Does Not, Mean

This record documents a completed study of combined haploidentical-cord blood transplantation in adults and children, with engraftment as the primary objective and GVHD and survival as secondary areas of interest. It gives a detailed description of the primary endpoint, including graft-failure criteria and treatment of death before engraftment as a competing risk. It also records adverse-event counts and selected serious-event terms.

However, the primary outcome estimate is not reported in the registry record. The title describes the percentage with neutrophil engraftment, while the endpoint description says cumulative incidence of graft failure was reported. The record does not include the estimate, its confidence interval bounds, or the event count. It also does not report numerical results for GVHD or survival. Thus, the registry record cannot establish the observed frequency or precision of these outcomes.

The non-randomized, single-group design does not support a like-for-like treatment comparison. Outcomes in the study group cannot be attributed to transplantation alone based on this record, and there is no randomized comparator from which to estimate a comparative effect. The listed safety events should likewise not be interpreted as proof of causation.

The record does not report enough detail to assess how treatment regimens were assigned, how risk groups were defined beyond the remission description, or which participants contributed to each outcome analysis. It also does not report a statistical analysis plan or missing-data methods. These gaps limit the strength and reproducibility of any interpretation. The evidence available from the registry is therefore primarily about the study’s design, its intended outcomes, and its recorded safety summary, rather than the magnitude of treatment outcomes.

14. Why This Trial Matters Statistically

This study raises statistical issues that are especially relevant to transplantation research. Engraftment is an event that occurs over follow-up, and the endpoint description explicitly recognizes that death before engraftment can prevent observation of the outcome. Treating death as a competing risk is conceptually important when estimating incidence because it distinguishes participants who remain at risk from those who can no longer experience the event.

The registry also illustrates why outcome labels and definitions need to be read together. The primary outcome title refers to neutrophil engraftment, whereas its description refers to cumulative incidence of graft failure. Those outcomes are related but not interchangeable. The description supplies operational criteria for failure, yet the record does not include a numerical result that clarifies the reported direction or magnitude of the primary endpoint.

Design is equally important. A non-randomized, single-group study can contribute descriptive information about participants treated in a clinical setting, but it cannot provide the protection against confounding that randomization offers in a comparative trial. Treatment regimens and risk-group descriptions are recorded, but the allocation details are not. This makes clear reporting of the population, intervention, analysis denominator, and outcome methods essential for interpretation.

Finally, transparent reporting of estimates and uncertainty is necessary to judge how informative an outcome is. A confidence interval is identified for the primary endpoint, but its bounds are not reported. The primary and secondary outcome values are also absent. Without those results, readers can understand the intended questions and some safety entries, but cannot evaluate the magnitude or precision of the clinical outcomes.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpreting this record is the absence of numerical primary and secondary outcome results. The primary endpoint’s title and description emphasize different but related quantities—engraftment and graft failure—and the record does not report an estimate or confidence interval that would clarify the posted result. Although the endpoint description includes failure criteria and competing-risk language, it does not identify the estimator or provide event counts.

The registered design is non-randomized and single-group, so there is no randomized comparator for a controlled estimate of comparative outcomes. The record lists multiple intervention components and describes a remission group, but the high-risk group descriptions are blank. It does not explain treatment allocation, how risk groups were determined, or how each regimen relates to those groups.

The registry does not report participant characteristics, outcome-specific analysis populations, missing-data handling, follow-up completeness, or a statistical analysis plan. It also does not report multiplicity procedures, interim analyses, or the methods used for secondary survival and GVHD outcomes. Safety reporting lacks a stated timeframe, attribution information, and details linking event-term percentages to counts or denominators. These omissions restrict assessment of precision, bias, and the scope of the safety summary.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Combined Haploidentical-Cord Blood Transplantation for Adults and Children — NCT00943800.
• Registry record last updated 2021-01-27; status last verified 2021-01.
• Results first posted 2020-10-27.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed, non-randomized, single-group study of combined haploidentical-cord blood transplantation for adults and children with leukemia, myelodysplastic syndrome, multiple myeloma, or lymphoma. Enrollment is listed as 87, and the sponsor is the University of Chicago. The primary objective concerns engraftment; secondary outcomes concern acute and chronic GVHD and survival at 2 years and 5 years.

The primary endpoint description defines graft failure and notes death before engraftment as a competing risk, but the numerical primary result and confidence interval are not reported in the registry record. Numerical GVHD and survival results are also not reported. Safety entries list 24 affected by serious adverse events among 87 at risk, 0 affected for other adverse events among 87 at risk, and 18 deaths, with selected serious-event terms and percentages. The record does not establish causal attribution or provide a randomized comparison.