Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation (NCT01319851), a na na study. The primary outcome is Feasibility of Alefacept Pre-conditioning, Measured by Number of Subjects With Full Donor Engraftment.

2. Clinical Question

The study addressed a proposed challenge in transplantation: a recipient sensitized to donor-cell proteins after transfusions may have immune memory cells that contribute to graft rejection. The registry’s rationale describes alefacept as a drug intended to selectively deplete such cells, and the pilot study was intended to begin assessing its use in a low-dose conditioning regimen. That rationale is not itself evidence that sensitization was changed or that rejection was prevented in this study.

The enrollment was 3, and the study status is terminated. Those details set a narrow context for interpreting the project: it is a small pilot record rather than a controlled estimate of comparative treatment effects. The registry record does not report the primary outcome count, participant-level disease breakdown, or a comparator-based estimate.

3. Trial Design

This was a single-group, open-label study: the registry lists a single-group model and masking as none. Allocation is listed as NA, consistent with the absence of a randomized allocation between treatment arms. The listed intervention was alefacept, and the enrollment was 3. The study phase is listed as NA.

The intended participants were children with non-malignant diseases who had been multiply transfused and were undergoing allogeneic hematopoietic stem cell transplantation. The registry lists a broad set of conditions, including inherited blood disorders, immune deficiencies, and marrow failure conditions. It does not report how the enrolled participants were distributed among these diagnoses, their baseline characteristics, or the eligibility criteria in detail.

The intervention description specifies intravenous alefacept at 0.5 mg/kg/dose. The first dose was split across days -40 and -39; the remaining doses were scheduled on days -33, -26, -19, and -12. The registry describes this as weekly dosing for 5 doses. The study concerned adding alefacept to a low-dose conditioning approach, but detailed conditioning components are not reported in the registry record.

The recorded start was 2010-09, and primary completion was 2013-09. The status is terminated. The registry record does not report why the study was terminated, whether all planned follow-up was completed, or whether termination changed the planned analyses.

There is no control arm against which to assess the effects of alefacept. A single-group study can describe what was observed among its participants, but it cannot separate an intervention effect from other influences using a concurrent randomized comparison. The registry record does not report a statistical plan, a sample-size justification, or interim analyses. Those omissions make it important to distinguish the stated study aim from evidence about comparative efficacy or safety.

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.

Before assignment: One subject with Fanconi Anemia (FA) received fludarabine (Flu) 25 mg/m2 on days -10 to -5 and cyclophosphamide (Cy) 10 mg/kg on days -5 to -2. The other two subjects received Flu 25 mg/m2 on days -6 to -1, Cy 50 mg/kg on day -2, and low-dose total body irradiation(TBI; 200 cGy) on day -1.

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 Feasibility of Alefacept Pre-conditioning, Measured by Number of Subjects With Full Donor Engraftment, measured over Two years post-transplant.

The primary endpoint is described as feasibility measured by the number of subjects with full donor engraftment. It is a participant count, and its timeframe is two years post-transplant. The registry description says participants received alefacept before transplantation and were followed for at least two years after transplantation to assess successful engraftment.

Engraftment is relevant to the study’s stated rationale because the investigators sought to determine whether alefacept could be incorporated into a lower-dose conditioning regimen while addressing the concern of graft rejection. In a pilot study, a feasibility endpoint can help describe whether the intended clinical process and outcome were observed in the enrolled group. It does not, by itself, establish that alefacept caused the outcome or that it is better than another regimen.

The endpoint’s result is not reported in the registry record. Although enrollment is listed as 3, the record does not give the number who achieved full donor engraftment, the participant-level follow-up status, or an uncertainty estimate for this endpoint. It also does not define the operational criteria used to classify full donor engraftment. These missing details prevent a reader from determining the observed feasibility result from the registry record alone.

The record lists secondary outcomes concerning regimen-related toxicity, neutrophil engraftment, donor chimerism, and acute and chronic graft-versus-host disease. These outcomes offer additional descriptions of transplantation outcomes and complications, but their results are not reported in the registry record. Their presence does not substitute for the missing primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a single-group pilot, the central statistical description would ordinarily be the number of participants meeting the endpoint, together with the number assessed and a measure of uncertainty. The registry identifies the primary outcome as a participant count for full donor engraftment, but the observed count and an uncertainty estimate are not reported in the registry record. Thus, there is no posted primary estimate to interpret statistically.

What does a participant count describe?

A count records how many participants met a specified outcome definition. A count alone is not a rate or a comparative effect. To interpret a count, a reader needs its denominator, the outcome definition, and information about whether all enrolled participants were assessed. The registry gives enrollment of 3, but does not report the primary outcome count or assessment details. No endpoint percentage or rate can therefore be inferred from the record.

For binary outcomes, such as whether a participant experienced an event, a proportion can summarize the observed frequency in a defined group. In small samples, that proportion can be unstable: a change in one participant’s status can materially alter the estimate. A confidence interval expresses uncertainty around an estimate under a statistical model; it is not a range that guarantees where the underlying value lies. No confidence interval for the primary endpoint is reported in the registry record.

Why does the single-group design matter?

A single-group study measures outcomes among participants who received the intervention, but it does not directly estimate the difference between intervention and control groups. Without a concurrent comparison group, observed outcomes may reflect the intervention, the underlying condition, transplantation and conditioning, follow-up practices, or other factors. This is a general limitation of uncontrolled designs, not a claim about what caused any particular outcome in this study.

Random allocation can support a fair comparison by balancing prognostic factors across groups on average. This study lists allocation as NA and its model as single-group, so a randomized contrast is not available. The study is also listed as having no masking. The registry record does not report whether outcome assessment used other safeguards against subjective judgment.

What can the safety counts tell a reader?

The adverse-event entry reports participants at risk and affected for serious and other events in the alefacept group. These counts are descriptive observations, not estimates of excess risk relative to a comparator. A serious-event term may also be recorded for more than one participant or alongside another term; without participant-level information, term counts should not be assumed to represent mutually exclusive people or events. The registry lists stomatitis and chronic graft-versus-host disease as top serious terms, each at 66.7%, but does not provide further detail on the percentage calculation or event-level overlap.

Over-dispersion is a general concern when counts vary more than a statistical model expects. For a very small group, the record does not offer enough information to assess a count model or estimate how much variability exceeds a model assumption. More generally, rare or severe outcomes can be difficult to characterize precisely in small studies, even when the events are clinically important.

How should planning illustrations be read?

The sample-size illustrations are planning calculations based on the observed effect, not the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is stated as a fraction of the observed effect. For time-to-event outcomes, the illustrations express the total number of events, using the Schoenfeld approach; other illustrations express participants per arm. These are hypothetical planning quantities for a future comparison, not outcomes observed in this study and not evidence of observed power.

Because the registry record does not report the primary endpoint result or a comparison effect, the planning illustrations cannot be interpreted as validating the present study’s design or as evidence that a future study would reproduce an effect. A planning calculation depends on its assumptions, including the effect targeted. It does not establish that the assumed effect is credible, nor does it replace a protocol-based sample-size justification. The registry record does not report such a justification.

What is absent from the analysis record?

The registry reports zero analyses. It does not report a statistical analysis plan, a model for the primary endpoint, a method for calculating uncertainty, or a prespecified approach to missing observations. It is therefore not possible to attribute any particular inferential method to the investigators. General statistical descriptions above explain how such results are often interpreted; they are not a statement that the study used those methods.

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("Alefacept")
n      <- c(3)
events <- c(3)
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  Alefacept  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry reports seven outcome measures: the primary full-donor-engraftment endpoint and secondary outcomes concerning regimen-related toxicity, neutrophil engraftment, donor chimerism, and acute and chronic graft-versus-host disease. It reports zero analyses, and results for the primary and secondary outcomes are not reported in the registry record.

When a study examines multiple outcomes, the chance of at least one apparently unusual result can increase if many statistical tests are conducted. This is the general issue of multiplicity. Possible approaches include identifying a primary outcome in advance, using a testing hierarchy, or adjusting inference across outcomes. The registry identifies a primary endpoint but does not report a multiplicity strategy or statistical plan, so it is not possible to determine how multiple outcomes were handled.

Missing-data handling is also not reported in the registry record. The record does not state whether all enrolled participants completed follow-up, whether any endpoint assessments were unavailable, or how missing outcome information would be treated. The primary outcome description refers to follow-up for at least two years after transplantation, but this does not establish that every participant had complete follow-up or that the endpoint result was available for everyone.

Analysis populations are not defined in the registry record. It does not state whether analyses were intended to include all enrolled participants, only those who underwent transplantation, or another specified group. Because the primary outcome count and analysis denominator are not reported, the reader cannot assess how the endpoint was analyzed or whether exclusions affected its interpretation.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stomatitis (66.7%), chronic graft versus host disease (66.7%).

The alefacept group’s adverse-event entry lists 3 at risk and 2 affected for serious events, and 3 at risk and 2 affected for other events. These are category-specific figures. They do not indicate whether the same participants were affected in both categories, so they should not be added together or interpreted as a count of distinct participants.

The listed top serious terms are stomatitis and chronic graft-versus-host disease, both reported as 66.7%. These percentages are registry entries; the record does not provide event-level detail, timing, duration, or enough information to determine whether the terms overlapped in participants. The deaths field is not reported in the registry record, which should not be interpreted as a reported count of zero.

These figures describe events recorded for participants in a single-group study. They do not establish that alefacept caused the events, and without a comparator they cannot quantify how event frequency differs from another treatment or from the background risks associated with the disease and transplantation. Given the small enrollment, the figures should be read as observations from this pilot rather than precise estimates of safety in a broader population.

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

The registry record establishes that a pilot study was conducted to examine alefacept before allogeneic hematopoietic stem cell transplantation in children with non-malignant diseases who had been multiply transfused. It records a single-group design, enrollment of 3, a terminated status, and a primary endpoint focused on the number of participants with full donor engraftment. It also records selected adverse-event figures.

The record does not report the primary endpoint result or results for the listed secondary outcomes. Therefore, it does not show how many participants achieved full donor engraftment, how the endpoint was distributed, or how outcomes varied by diagnosis. The missing outcome result cannot be interpreted as a positive or negative finding. Termination status alone also does not explain the study’s outcome or why it ended; the reason is not reported in the registry record.

The design cannot support a randomized comparison because it has no control group. Even if outcome results were available, outcomes in this group alone would not establish what would have happened under another regimen. The study’s rationale about transfusion-related sensitization and possible graft rejection describes the question motivating the work, not proof that alefacept changed sensitization or prevented rejection.

The adverse-event entries describe observations, not causal effects. They do not establish that alefacept caused stomatitis, chronic graft-versus-host disease, or any other event. Nor do they determine the comparative safety of the regimen. Small enrollment and missing participant-level detail further limit how broadly the entries can be interpreted.

The study can be understood as a pilot addressing feasibility in a high-risk transplantation context, but the registry record does not provide the outcome evidence needed to judge the primary question. It does not demonstrate benefit or lack of benefit, and it does not establish safety or lack of safety. Any stronger conclusion would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because it asks a focused feasibility question in a population and treatment setting described as challenging, while using a single-group pilot design. Such a design can be useful for documenting whether a process was undertaken and for observing outcomes that may inform later research. It is not designed to supply the same kind of comparative evidence as a randomized trial.

Its primary endpoint is stated as a participant count for full donor engraftment, which is a direct outcome relevant to the study’s rationale. But a useful endpoint definition must be paired with reported results and an interpretable denominator. The registry record does not report the endpoint result, its operational criteria, or an uncertainty estimate. That gap means the central feasibility question cannot be answered from the posted registry results.

The safety information also illustrates the difference between observed frequency and comparative risk. The record reports affected participants and serious-event terms, but a single group cannot establish whether events are more common than under an alternative regimen. Descriptive safety reporting remains important, particularly in transplantation, yet it should not be mistaken for a causal or comparative analysis.

The small enrollment makes precision especially important. A count from a small group can change substantially in relative terms when an individual outcome differs, so estimates require cautious interpretation and uncertainty information. No primary uncertainty estimate is reported. The registry’s planning illustrations are explicitly based on the observed effect and hypothetical two-arm assumptions; they are not evidence of power in this pilot or proof that a particular future sample size is adequate.

Finally, the absence of a reported analysis plan and outcome results limits reproducibility and critical appraisal. The record identifies the intended question and outcomes, but does not show how those outcomes were analyzed. This distinction matters: a well-motivated research question, an endpoint, and a safety listing are not substitutes for complete results and a transparent statistical analysis.

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 trial-specific limitation is that the registry record does not report the primary endpoint result. It also does not report results for the secondary outcomes, despite listing measures related to toxicity, engraftment, donor chimerism, and graft-versus-host disease. Without those results, the record cannot answer the stated feasibility question or provide a fuller account of transplant outcomes.

Enrollment was 3, and there was no concurrent comparator group. The study therefore offers limited scope for estimating outcome frequencies precisely and cannot provide a randomized comparison with another conditioning approach. The broad set of listed conditions also means the registry record does not establish how representative the enrolled group was of any one diagnosis or how outcomes might differ across conditions.

The record does not report baseline participant characteristics, detailed eligibility criteria, participant-level disease distribution, or the operational definition of full donor engraftment. It does not give the number assessed for the primary endpoint or clarify follow-up completeness. Although the endpoint description refers to follow-up for at least two years after transplantation, completion by each participant is not reported.

The status is terminated, but the reason for termination is not reported in the registry record. A statistical analysis plan, sample-size justification, interim analyses, analysis populations, missing-data procedures, and multiplicity handling are also not reported. The adverse-event listing lacks participant-level detail about event timing, duration, overlap, and attribution. These gaps constrain both outcome interpretation and assessment of how the study was conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation — NCT01319851.
• Registry record last updated 2017-07-27; status last verified 2017-07.
• Results first posted 2015-03-09.
• 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 record describes a pilot study of alefacept before allogeneic hematopoietic stem cell transplantation for multiply transfused children with non-malignant diseases. The study was single-group, had no masking, listed allocation and phase as NA, enrolled 3, and is marked terminated. The recorded start was 2010-09, with primary completion in 2013-09.

The primary endpoint was the number of participants with full donor engraftment, with a timeframe of two years post-transplant. The registry record does not report the result. It lists secondary outcomes involving toxicity, neutrophil engraftment, donor chimerism, and graft-versus-host disease, but does not report their results or analyses.

The alefacept group’s serious-event entry lists 2 affected among 3 at risk; its other-event entry also lists 2 affected among 3 at risk. Stomatitis and chronic graft-versus-host disease are each listed among the top serious terms at 66.7%. These figures are descriptive and do not establish causation or comparative safety.