T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts (NCT00368355), a non-randomized phase 2 study. The primary outcome is Engraftment Rate After Transplant.

2. Clinical Question

The clinical question is whether engraftment was observed after this transplant approach, and how the registry characterized that outcome. The posted record also lists early post-transplant toxicities, severe graft-versus-host disease (GVHD), acute GVHD, and chronic GVHD as secondary outcomes. It describes the concern that haploidentical transplantation can involve GVHD, transplant failure, and delayed immune recovery, but those general concerns are not themselves results of this study.

The two device groups offer a descriptive view of participants whose grafts were processed using different devices. They do not establish a randomized device comparison. The registry record does not describe how device assignment was decided or provide information that would establish comparable groups. Accordingly, the central question is about the reported outcomes in this study, not proof that one device or treatment strategy is better than another.

3. Trial Design

This is a phase 2 study sponsored by Baylor College of Medicine. The registry records the study as completed, with enrollment of 46, a start date of 2000-04, and primary completion in 2015-11. It lists non-randomized allocation, no masking, and a single-group model. At the same time, the record presents two device groups: CLINIMACS and ISOLEX. These registry descriptions should be read together without treating the groups as randomized arms.

Both group descriptions include conditioning with Ara-C, cyclophosphamide, Campath-1H, and total body irradiation, followed by a T-cell-depleted stem cell infusion processed with the named device. The registry summary describes use of a close relative’s stem cells when a perfectly matched donor was unavailable and the disease did not permit enough time to identify another donor. The listed conditions span malignant, hematologic, and immune-related diagnoses, so the enrolled population was clinically varied.

The primary endpoint was engraftment rate after transplant, expressed as a percentage of participants and assessed over 28 days. The registry defines the evaluable population in relation to transplant and the observation period: a participant was evaluable if they underwent transplant and either completed 28 days of observation or engrafted. It also notes that one participant in the CLINIMACS group did not undergo transplant and one in the ISOLEX group died 5 days after transplant. The remaining population description is incomplete in the registry record, and a final evaluable count is not reported in the registry record.

The registry lists 7 outcome measures and 0 analyses. It does not report the allocation procedure, a protocol-defined statistical plan, or details of any planned comparison between device groups. A sample-size justification is not reported in the registry record. Because allocation was non-randomized and the record characterizes the model as single-group, differences between the device groups should be interpreted descriptively, with potential group differences and treatment-selection processes unresolved.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: A participant is evaluable for engraftment if the participant underwent transplant and either completed 28 days observation or engrafted. Of the 46 participants at baseline, one in CLINIMACS group did not undergo transplant and one in ISOLEX group died 5 days after transplant.Thus, 2 participants were not included in the analysis.

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.

Population: Participants who had their donor stem cells processed using the ISOLEX or CliniMACS CD34 Reagent System and started preparative regimen were included in this analysis.

6. Primary Endpoint

The registry lists the primary outcome as Engraftment Rate After Transplant, measured over 28 days.

The primary endpoint measures whether hematopoietic engraftment occurred after transplant. The registry expresses the measure as a percentage of participants and defines engraftment as the first day absolute neutrophil counts exceeded 0.5 X 10^9/ml. The specified timeframe is 28 days. The record’s evaluability definition includes participants who underwent transplant and either completed 28 days of observation or engrafted.

Engraftment is a clinically relevant early transplant outcome because it captures recovery of blood-cell production after graft infusion. In general, a clearly defined endpoint makes it possible to apply the same event rule across participants and to specify what counts as reaching the outcome. The threshold and time window make the endpoint more concrete than a broad statement that blood counts recovered. This is a general explanation of endpoint design, not a claim about the outcome observed in this trial.

The registry record does not report the number or percentage of participants who engrafted, nor does it report the stated confidence interval. Therefore, the endpoint’s observed frequency and statistical precision are not reported in the registry record. The available description also does not establish whether all participants were assessed in the same way beyond the stated evaluability rule. One participant in the CLINIMACS group did not undergo transplant, and one in the ISOLEX group died 5 days after transplant; the registry’s partial population text identifies these cases but does not give a completed evaluable denominator.

Since the result itself is absent, no conclusion about the observed engraftment rate can be drawn from the primary endpoint entry. The endpoint definition explains what was intended to be measured; it does not substitute for the missing outcome estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint measure?

The endpoint is the percentage of participants with hematopoietic engraftment after transplant. The registry defines engraftment by the first day absolute neutrophil counts exceeded 0.5 X 10^9/ml, within a 28-day timeframe. In general, an endpoint definition tells readers which events count and when they are assessed. A threshold-based definition can improve consistency, because participants are evaluated against a stated criterion rather than an informal impression of recovery. The definition does not, by itself, show how many participants met that criterion.

The record says a participant was evaluable for engraftment if transplant occurred and the participant either completed 28 days of observation or engrafted. This rule combines an observation-duration condition with an event-based condition: someone who engrafted could be evaluable without completing the full observation window. The record notes one participant in the CLINIMACS group did not undergo transplant and one in the ISOLEX group died 5 days after transplant. The population description is truncated after those details, and a final evaluable denominator is not reported in the registry record.

What does a confidence interval contribute?

In general, a confidence interval describes the statistical uncertainty around an estimated quantity. For a percentage, it gives a range of values compatible with the observed data under the interval’s method and assumptions. A narrower interval usually indicates greater precision, while a wider interval indicates greater uncertainty. A confidence interval is not a guarantee that the true value lies within its limits, and it does not correct for biased group assignment, incomplete follow-up, or a poorly defined endpoint.

The endpoint entry names a 95% confidence interval, but the interval limits and point estimate are not reported in the registry record. As a result, no statement about the engraftment estimate’s precision is possible. The interval method is also not reported in the registry record. No recalculated estimate is appropriate without the primary outcome count and denominator.

Why does the design matter for comparisons?

Random allocation is a general method for balancing known and unknown participant characteristics between treatment groups, on average. In a non-randomized study, group membership may be related to clinical characteristics, timing, availability, or other factors. Unless those factors are measured and addressed appropriately, an observed group difference can reflect those differences rather than the intervention itself. The allocation process and any adjustment strategy are not reported in the registry record.

Here, the record describes non-randomized allocation and a single-group model, while also listing CLINIMACS and ISOLEX device groups. It specifically warns that the arms are not a like-for-like control comparison. Thus, group-specific counts can be described, but the record does not support treating the groups as exchangeable controls or attributing a difference to device processing. A formal comparative analysis, including any adjustment for baseline differences, is not reported in the registry record.

How should binary outcome counts be read?

For an outcome recorded as a percentage of participants, the basic descriptive information is the number meeting the outcome and the number eligible for assessment. The percentage depends on both. In general, the denominator must be understood before comparing percentages, especially when some participants did not undergo transplant, died early, or had incomplete observation. The registry’s partial evaluability description matters for exactly this reason. Since the engraftment count and completed denominator are absent, the primary percentage cannot be checked or reconstructed.

Safety entries also need their denominators interpreted carefully. The registry gives serious and other adverse event counts alongside numbers at risk for each device group. These support a description of how many participants were recorded as affected within the reported group. They do not provide person-time, event timing, or a full account of repeated events. In general, a participant count and an event count are not interchangeable: one participant may experience more than one event, while a participant-level affected count records whether the participant had at least one event under the registry’s coding rule.

What does over-dispersion mean in general?

Over-dispersion is a general statistical issue that arises when outcome variability is greater than a model assumes. If a model understates variability, standard errors can be too small and confidence intervals too narrow. This concept can matter for count outcomes or clustered data, but the primary endpoint is described as a participant percentage. The registry does not report a statistical model or any assessment of over-dispersion, so no claim can be made that it was relevant to or addressed in this study.

What can planning illustrations say?

In general, a sample-size calculation can illustrate how many participants might be needed under stated assumptions about the effect to detect, significance level, allocation, and statistical method. Such a calculation is prospective planning, not a measure of what the completed study achieved. A planning illustration based on an observed effect is especially dependent on the observed estimate and can be unstable when that estimate is uncertain. It is not observed power and cannot replace a confidence interval or an analysis of the trial’s outcome.

The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. Those assumptions are described as an illustration and not as the trial’s own design. The registry record does not report the trial’s sample-size justification or a statistical analysis plan. Since the primary effect estimate is not reported, planning quantities should not be interpreted as evidence about the outcome.

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("CLINIMACS Device", "ISOLEX Device")
n      <- c(17, 27)
events <- c(17, 27)
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  CLINIMACS Device  17  17  100.0  80.5  100.0  81.6  100.0  81.5  99.9
ARM  ISOLEX Device  27  27  100.0  87.2  100.0  87.5  100.0  87.7  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including engraftment as the primary endpoint and secondary outcomes concerning early post-transplant toxicities and GVHD. It records 0 analyses. The statistical plan for handling multiple outcomes is not reported in the registry record. In general, testing several outcomes can increase the chance of at least one apparently noteworthy result if no multiplicity strategy is specified. This general concern does not establish that such testing occurred in this study.

The record does not report whether any interim analyses were planned or performed, whether endpoints were ranked for interpretation, or whether a family-wise or other multiplicity adjustment was used. Those details are not reported in the registry record. With no outcome analyses or inferential results listed, there is no basis to assess how multiple testing may have been handled.

Missing-data methods are also not reported in the registry record. The primary endpoint population definition provides some information about evaluability, and the record notes that one participant in the CLINIMACS group did not undergo transplant and one in the ISOLEX group died 5 days after transplant. However, the available population text is incomplete and does not state a final denominator or explain how other incomplete observations were handled. It does not say whether missing outcomes were excluded, imputed, or treated in another way.

The record does not describe an intention-to-treat analysis or another named analysis population. Nor does it report whether adverse events were assessed in all enrolled participants or only those exposed to transplant, beyond the group-specific numbers at risk. These population definitions and handling rules are not reported in the registry record. Consequently, the completeness of outcome ascertainment and the relationship between the reported denominators and enrollment cannot be fully evaluated.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infection without neutropenia (55.6%), hemorrhage/bleeding with grade 3 or 4 thrombocytopenia (11.1%), catheter-related infection (11.1%), sgot (ast) (serum glutamic oxaloacetic transaminase) (7.1%), hypokalemia (7.1%).

The registry reports serious adverse events for 14 of 18 participants at risk in the CLINIMACS group and 15 of 28 at risk in the ISOLEX group. For other adverse events, it reports 13 of 18 and 23 of 28, respectively. Death counts are recorded as 2 in the CLINIMACS group and 4 in the ISOLEX group. These are group-level counts, not evidence that the device caused an event or death.

Among the leading serious adverse event terms, infection without neutropenia is listed at 55.6%. Hemorrhage or bleeding with grade 3 or 4 thrombocytopenia and catheter-related infection are each listed at 11.1%. SGOT (AST), hypokalemia, and hemorrhagic cystitis are each listed at 7.1%. The registry does not report the detailed denominator for these term percentages in the available record, or whether participants could contribute to multiple terms.

In general, safety counts describe what was recorded under the study’s reporting and coding procedures. Interpretation also depends on the event definitions, observation time, severity rules, and whether repeated events are counted. These details are not reported in the registry record. Because allocation was non-randomized and the record warns against treating the arms as like-for-like controls, the counts should not be read as a comparative risk estimate.

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

The record establishes that a completed phase 2 study enrolled 46 participants and examined a transplant approach involving intensive conditioning followed by T-cell-depleted stem cell infusion. It identifies engraftment rate after transplant as the primary endpoint, defines the event using an absolute neutrophil count threshold, and specifies a 28-day timeframe. It also lists secondary outcomes related to toxicity and GVHD and reports descriptive adverse event counts for the CLINIMACS and ISOLEX groups.

Those details describe the study’s aim and recorded outcomes, but the central primary result is not reported in the registry record. There is no reported engraftment percentage, event count, or confidence interval to establish the observed rate or its precision. The record therefore cannot show how often engraftment occurred within the endpoint window or how uncertain that estimate was. The description of the endpoint is not a substitute for the endpoint result.

The record also does not establish a causal comparison between device groups. Allocation was non-randomized, the model is recorded as single-group, and the registry cautions that the arms are not a like-for-like control comparison. Differences in the safety counts cannot be attributed to the device without adequate design and analysis information. The allocation process, group comparability, adjustment methods, and comparative analyses are not reported in the registry record.

In general, a trial result is most informative when the outcome definition, denominator, estimate, uncertainty, and analysis population are all clear. The registry supplies some design and endpoint definitions but not the primary estimate or a full analysis account. The safety counts are useful as descriptive registry entries, but the record does not provide the details needed to establish event rates over time or compare risk fairly between groups.

Accordingly, the record supports a cautious account of what was planned and which events were listed, not a conclusion that the transplant approach or either processing device did or did not work. It also does not establish the comparative safety of the devices. The missing results and methodological details limit interpretation; they should not be filled in by inference from the study title, rationale, or group counts.

14. Why This Trial Matters Statistically

This study raises statistical issues common to clinical research where a complex intervention is evaluated in a small, clinically varied population and treatment allocation is not randomized. Participants had a range of listed conditions and received intensive conditioning as well as a T-cell-depleted stem cell infusion. Any observed outcome could reflect multiple aspects of care and participant characteristics, not only the graft-processing device. This makes clear separation of descriptive findings from causal claims especially important.

The registry’s combination of a single-group model, non-randomized allocation, and two reported device groups illustrates why design labels and arm descriptions need to be read together. Listing two groups does not make them randomized controls. Without an allocation explanation and evidence of comparability, group differences may have several interpretations. The registry itself cautions that the groups are not a like-for-like control comparison.

The primary endpoint is clearly defined in terms of an event threshold and assessment window, which is a useful feature for reproducible outcome assessment. Yet a well-defined endpoint cannot answer the clinical question without the observed estimate and its uncertainty. Their absence means that the main statistical result cannot be evaluated, even though the endpoint description is available.

The incomplete evaluability description also highlights how participant flow affects outcome interpretation. The record identifies one participant in each device group with a different reason for not fitting the usual observation pattern, but does not provide the final evaluable denominators or a full missing-data account. This makes it difficult to determine precisely which participants contribute to the primary outcome estimate.

Finally, the safety entries show why event counts require context: definitions, denominators, follow-up, and possible overlap all matter. In this record, those details are limited. The trial is therefore statistically instructive not because it supplies a complete efficacy comparison, but because it demonstrates how design, outcome reporting, and analysis transparency shape what readers can responsibly conclude.

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 engraftment result. It provides the endpoint definition and names a 95% confidence interval, but the estimate, interval limits, and event count are not reported in the registry record. This prevents assessment of the endpoint’s observed frequency and precision.

The study design information is also limited. Allocation is recorded as non-randomized, the model as single-group, and two device groups are nevertheless listed. The record warns that the arms are not a like-for-like control comparison. How participants came to receive one device or the other, whether baseline characteristics differed, and whether any confounding adjustment was used are not reported in the registry record.

The participant-flow account is incomplete. The record gives enrollment of 46 and identifies one CLINIMACS participant who did not undergo transplant and one ISOLEX participant who died 5 days after transplant. It does not provide the completed evaluable population count or a full account of other exclusions, loss to follow-up, or missing outcome data. The analysis population and missing-data methods are not reported in the registry record.

For safety, counts are available, but event definitions, timing, follow-up duration, recurrent-event handling, and the denominators underlying the listed serious-event term percentages are not fully described. No inferential analyses are recorded, so statistical comparison or adjustment cannot be assessed. A sample-size justification, interim-analysis plan, and multiplicity strategy are not reported in the registry record.

These limitations mean that the available information is descriptive and incomplete. They do not establish that outcomes were poor or favorable; rather, the record does not supply the information needed to evaluate the primary estimate or make reliable comparative claims.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts — NCT00368355.
• Registry record last updated 2020-01-21; status last verified 2020-01.
• Results first posted 2020-01-21.
• 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

NCT00368355 is a completed phase 2 study sponsored by Baylor College of Medicine, with enrollment of 46. The registry records non-randomized allocation, no masking, and a single-group model, while listing CLINIMACS and ISOLEX device groups. Both group descriptions include Ara-C, cyclophosphamide, Campath-1H, total body irradiation, and T-cell-depleted stem cell infusion.

The primary endpoint is engraftment rate after transplant, defined by the first day absolute neutrophil counts exceeded 0.5 X 10^9/ml, within 28 days. The primary outcome estimate and confidence interval are not reported in the registry record. Safety entries include group-specific serious and other adverse event counts, deaths, and selected serious adverse event terms.

The registry lists 7 outcome measures and 0 analyses. It cautions that the device groups are not a like-for-like control comparison. The final evaluable population, full missing-data handling, statistical plan, and sample-size justification are not reported in the registry record.