Allogeneic Transplantation From Related Haploidentical Donors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Allogeneic Transplantation From Related Haploidentical Donors (NCT00185692), a na phase 2 study. The primary outcome is Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning.

2. Clinical Question

3. Trial Design

This was a completed phase 2 study sponsored by Stanford University. The registry lists a start date of 2000-08 and primary completion of 2010-12. Enrollment was 16. The design is classified as single-group, allocation as not applicable, and masking as none. Those classifications indicate that the registry does not describe a randomized, masked comparison between intervention arms.

The transplant approach involved positively selected CD34+ hematopoietic cells from a related haploidentical donor, with a non-myeloablative conditioning regimen involving total lymphoid irradiation and antithymocyte globulin. The arm description gives a sequence of conditioning and additional medicines. It lists cyclosporine and mycophenolate mofetil, while the intervention list also includes G-CSF, Solumedrol, acetaminophen, and diphenhydramine. The registry does not report enough detail to infer how each listed intervention was administered to every participant.

The study purpose was to evaluate feasibility and safety. The primary outcome concerns donor-cell engraftment, and the secondary outcome concerns risk of acute graft-versus-host disease of grades 2-4 from transplant through day 90 post-transplant. The primary outcome description specifies assessment of engraftment by day 90, while its listed timeframe is 100 days. That difference in stated timing is part of the registry record; additional clarification is not reported.

Because there is one study group, outcomes can describe what was recorded among participants receiving this approach, but the design cannot directly distinguish the effects of the transplant regimen from other influences. The registry record does not report a statistical analysis plan, analysis populations, outcome estimates, or results for the primary and secondary outcomes. No comparative conclusion can be drawn from a concurrent control contrast because none is described.

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 Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning, measured over 100 days.

The primary endpoint is a participant count for donor-cell engraftment after haploidentical CD34+ selected blood stem-cell transplantation. The registry defines an event as donor-cell engraftment greater than 95% by day 90 after transplant. The outcome timeframe is listed as 100 days, so the record contains two related but not identical descriptions of when the primary endpoint is assessed.

Engraftment is relevant to this transplant approach because the procedure depends on donor-derived blood-forming cells becoming established. As a general statistical concept, a binary endpoint records whether each participant meets a specified event definition, and a count reports how many meet it. The interpretation depends on the event definition, assessment window, and the participants included in the analysis. The registry record does not report the number who achieved engraftment, the number assessed, or an estimate of the proportion achieving the endpoint.

The endpoint is registered as a count rather than a time-to-event measure. Although the description gives a day-based assessment, it does not report a time-to-engraftment analysis. The registry also does not explain how missing assessments, competing events, or deviations from the specified threshold were handled. Those details matter when interpreting an observed count, but they are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are difficult to assess because the registry record does not report a detailed analysis plan or analyses. The study is classified as single-group, with allocation not applicable and masking none. The registry lists two outcome measures and zero analyses. These registry entries describe what is recorded; they do not reveal whether additional analyses were conducted outside the registry record.

What does a single-group outcome estimate describe?

In general, an outcome count in a single-group study describes the participants who were observed under the study approach. For a binary endpoint, each participant is classified according to whether the event definition was met, and the count records the number meeting it. A proportion could also be reported, but its interpretation depends on the denominator: the participants enrolled, the participants assessed, or another explicitly defined analysis population. The registry record does not report the primary endpoint count or its denominator, so neither an outcome proportion nor its precision can be assessed.

A single-group result is not a randomized treatment contrast. Without a concurrent comparator, the study cannot estimate the difference between outcomes under the transplant regimen and outcomes under another intervention. General statistical adjustment cannot create the missing randomized comparison, and the registry does not describe an adjusted analysis. Any observed outcome would therefore need to be interpreted as a description of this study group, rather than a causal comparison.

How should uncertainty be understood?

In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the method used. Its width depends on factors including the amount of information available and the variability of the observations. A confidence interval for a binary endpoint would require a reported event count and denominator, along with a specified method. The registry record does not provide the primary event count, denominator, or interval. Precision for the primary endpoint therefore cannot be evaluated from the registry entries reported.

A p-value would address compatibility between observed data and a specified null hypothesis under a statistical model; it would not state the probability that a treatment works. For this study, the registry record reports no primary-outcome p-value or hypothesis test, and the listed number of analyses is zero. No significance conclusion should be inferred from the design description or enrollment figure.

What do the planning assumptions mean?

The sample-size assumptions describe a planning illustration based on an observed effect, not the original trial design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. This hypothetical setup differs from the actual single-group study. Such planning estimates are not observed power and do not indicate the probability that the completed study detected an effect. The registry record does not report the trial's own sample-size justification or design assumptions.

When planning illustrations are based on an observed effect, their values depend on the effect chosen as the planning target. The assumptions are not evidence that a treatment effect was established, and they do not remedy the absence of an outcome estimate or control group. No calculated planning values are described in the registry record, so no sample-size target or power estimate can be interpreted from the available record.

Why does the endpoint definition matter?

The primary endpoint uses a threshold: donor-cell engraftment greater than 95% by day 90. A threshold converts a measured biological quantity into an event classification. The classification can be clear only if the underlying measurement, threshold application, and assessment window are consistently specified. The registry also lists a timeframe of 100 days. The difference between that timeframe and the day 90 description should be retained rather than silently resolved. The registry record does not report whether one timing description takes precedence, how measurements close to the threshold were treated, or whether assessments outside the stated window were allowed.

The secondary endpoint is described as risk of acute graft-versus-host disease of grades 2-4 from transplant until day 90. In general, a risk estimate requires a defined population, follow-up window, event definition, and handling of participants who do not complete follow-up. The registry does not provide the secondary outcome result or those analysis details. It is therefore not possible to reconstruct a risk estimate from the outcome title alone.

How should safety counts be interpreted statistically?

Safety summaries can distinguish the number at risk from the number affected, but the interpretation depends on how adverse events are defined and collected. The registry lists a serious-event group with 16 at risk and 14 affected. It separately lists Death as a serious term at 87.5%, while the death count is not reported. The record does not specify whether the percentage uses the group at risk, participants affected, or another denominator, and no denominator should be inferred. It also does not report event timing, recurrent-event handling, or whether a participant could contribute more than one serious event.

In general, sparse event data can yield considerable uncertainty, but no interval can be described without a specified estimate and method. These reported safety entries should not be used to infer an unreported primary-outcome result. More broadly, statistical interpretation requires the estimate, its denominator, the analysis population, and the method; several of these are not reported in the registry record.

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("Transplantation of CD34+ Cells")
n      <- c(16)
events <- c(4)
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  Transplantation of CD34+ Cells  16  4  25.0  7.3  52.4  10.2  49.5  10.3  49.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures: donor-cell engraftment as the primary outcome and acute graft-versus-host disease of grades 2-4 as a secondary outcome. It reports zero analyses. No multiplicity strategy is reported in the registry record. It is therefore not possible to determine whether any adjustment for testing multiple outcomes or analyses was planned or used. A listed secondary endpoint should not be treated as confirmatory evidence when the analysis and results are not reported.

Missing-data handling is not reported in the registry record. The record does not state how participants without an engraftment assessment were handled, whether follow-up was complete, or what rules determined inclusion in the primary analysis. It also does not report imputation, sensitivity analyses, or reasons for missing assessments. Without those details, the denominator and potential effect of missing outcomes cannot be evaluated.

The analysis population is not reported in the registry record. Enrollment was 16, but the record does not say whether the primary endpoint analysis included everyone enrolled, only those who received transplantation, or another defined group. It also does not describe exclusions or deviations from the endpoint assessment window.

The registry does not report an interim-analysis plan, stopping boundaries, or a prespecified statistical analysis plan. Their presence or absence cannot be inferred from the phase or design labels. These omissions limit assessment of how the reported outcomes, if available, would relate to prespecified analyses and how selective reporting might be evaluated.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: death (87.5%).

The registry lists one serious adverse event group, titled CD34+ Selected Hematopietic Cells. It reports 16 participants at risk and 14 affected. The serious-event term Death is listed with 87.5%. A separate death count is not reported in the registry record.

These entries should be kept distinct. The affected count describes the registry's serious adverse event group, while the Death entry is a listed serious term with a percentage. The record does not explain the percentage denominator, provide event dates, define the serious-event collection window, or state how multiple events in one participant were handled. It also does not report whether the 14 affected participants experienced the listed Death term or other serious events.

Accordingly, the figures describe registry safety reporting, but they do not provide a complete account of event types, timing, or participant-level outcomes. The percentage should not be converted into a count, and the missing death count should not be inferred from the percentage. These safety entries do not supply the absent primary engraftment result.

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

The registry record identifies a clinically specific transplant strategy and a primary question about donor-cell engraftment. It also records that the study was completed, phase 2, single-group, and open-label. The study purpose was to evaluate feasibility and safety in older patients or those with medical co-morbidities and indolent hematologic malignancies. These details describe the study's scope, not its outcome.

The record does not report how many participants achieved the primary engraftment endpoint, nor an estimate or measure of uncertainty. It therefore does not establish what the observed engraftment result was. The absence of a reported result should not be interpreted as either success or failure. The secondary acute graft-versus-host disease outcome is also listed without a result.

The single-group design means that any available outcome count would describe the experience of the study group, not a controlled difference between transplant approaches. The record does not include a comparator arm. It therefore cannot, on its own, show whether outcomes differ from those under another regimen or establish that the intervention caused a particular outcome.

The safety section records 16 participants at risk, 14 affected, and Death as a serious term at 87.5%, while the death count is not reported. The incomplete detail prevents a full interpretation of the safety profile or its timing. These entries should not be substituted for a systematic comparison of harms or for the missing primary endpoint result.

In statistical terms, the record is most informative about the question asked and the broad design used. It is not sufficient to quantify the primary outcome, assess its precision, evaluate missingness, or make comparative claims. The registry status of completed does not itself provide evidence about the direction or magnitude of an outcome.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between a clearly stated clinical endpoint and an interpretable result. The registry defines donor-cell engraftment using a threshold and a post-transplant assessment time, but does not report the endpoint count or an uncertainty estimate. Readers therefore need to separate the study's intended question from evidence about its observed outcome.

The design also matters. A single-group phase 2 study can describe feasibility and safety in the treated group, but it does not supply a concurrent contrast. That distinction is important when a registry entry is read as evidence for a particular transplant strategy: a group outcome, even when reported, is not the same as an effect relative to an alternative.

The timing descriptions emphasize the value of endpoint clarity. The primary outcome description specifies assessment by day 90, while the listed timeframe is 100 days. Without an explanation, that mismatch leaves uncertainty about the intended assessment window. The secondary outcome has its own stated period through day 90, but its result is also absent.

The safety entries are another useful statistical lesson. Counts at risk and affected, a serious term percentage, and a missing death count do not by themselves form a complete safety analysis. Denominators, definitions, timing, and event handling are needed to interpret such information responsibly. Overall, the record shows why design, endpoint specification, reporting completeness, and statistical uncertainty must be considered together.

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 primary limitation for interpretation is that the registry record does not report the primary outcome result. No engraftment count, denominator, proportion, interval, or test result is available in the record. The secondary outcome is also listed without a result. As a result, the central study questions cannot be answered from the reported outcome information.

The study is single-group and has no concurrent comparator. This limits interpretation to descriptive outcomes in the study group and prevents direct estimation of differences against another strategy. The registry also lists no masking, and does not report details that would allow assessment of how outcome ascertainment was conducted.

The primary endpoint has a timing ambiguity: its description says engraftment greater than 95% by day 90, while the timeframe is listed as 100 days. The registry does not explain the relationship between these statements. Further endpoint details, including assessment procedures and handling of missing or borderline measurements, are not reported in the registry record.

The analysis population and missing-data approach are not reported. Although enrollment was 16, the record does not state how many participants contributed to each outcome analysis. No detailed statistical analysis plan, multiplicity procedure, or interim-analysis information is reported. The registry lists zero analyses, which leaves no reported inferential results to evaluate.

Safety reporting is also limited. The record lists 16 at risk, 14 affected, Death at 87.5%, and no separately reported death count. It does not define the percentage denominator, describe the event collection period, or provide event-level detail. These omissions constrain both clinical and statistical interpretation of the safety entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Allogeneic Transplantation From Related Haploidentical Donors — NCT00185692.
• Registry record last updated 2019-12-04; status last verified 2015-01.
• Results first posted 2017-01-26.
• 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 phase 2 study sponsored by Stanford University, with enrollment of 16 and a single-group, unmasked design. It evaluated non-myeloablative hematopoietic cell transplantation using positively selected CD34+ cells from related haploidentical donors after total lymphoid irradiation and antithymocyte globulin conditioning. The primary endpoint was donor-cell engraftment greater than 95% by day 90, although the listed timeframe is 100 days. Acute graft-versus-host disease of grades 2-4 through day 90 was a secondary outcome. The registry record does not report either outcome result or a statistical analysis. Safety entries list 16 at risk, 14 affected, and Death as a serious term at 87.5%; the death count is not reported.