Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs (NCT00957931), a na phase 2 study. The primary outcome is Count of Participants With Stable Engraftment Post Hematopoietic Cell Transplantation (HCT).

2. Clinical Question

The registry record describes a pilot study of hematopoietic cell transplantation for people with high-risk sickle cell disease or other non-malignant red blood cell disorders, including thalassemia and Diamond-Blackfan anemia. Its summary focuses on patients without matched sibling donors and describes the use of unrelated-donor marrow or umbilical cord blood. The actual donor source used for each participant is not reported in the registry record.

The intervention combines transplantation with mesenchymal stromal cells. The official title calls the cells haplo-identical, while the listed interventions identify bone marrow transplantation and mesenchymal stromal cells. The registry record frames the clinical challenge as achieving engraftment while managing graft-versus-host disease and other complications. These are aims in the study description, not demonstrated findings.

3. Trial Design

This is a completed phase 2 study with a single-group model and an enrollment of 6. The registry record lists no allocation procedure and no masking. The study start is recorded as 2009-03, and primary completion as 2013-08. These design details describe the registry entry; they do not establish how every study procedure was carried out.

The listed interventions are bone marrow transplantation and mesenchymal stromal cells. The official title describes a reduced-intensity preparative regimen and haplo-identical mesenchymal stromal cells. The summary says that transplantation would use matched but unrelated marrow or umbilical cord blood, but the actual donor source and participant-level treatment details are not reported in the registry record. The arm description contains no further details.

A single-group design can describe outcomes among participants receiving a study intervention, but it cannot directly estimate how those outcomes compare with a concurrent untreated or alternative-treatment group. With no random allocation or comparator, differences from other populations or historical experience would also be vulnerable to differences in patient selection, care, and follow-up. No such comparison is reported in the registry record.

The primary outcome is a count of participants with stable engraftment, assessed up to one year. Secondary outcomes named in the record include overall survival and disease-free survival at six months and one year following transplantation. The record lists five outcome measures but provides no analysis results. Its status is completed; completion status alone does not establish that an endpoint was met or that outcomes were favorable.

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:

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 Count of Participants With Stable Engraftment Post Hematopoietic Cell Transplantation (HCT), measured over Up to 1 year.

The primary endpoint counts participants with stable engraftment after hematopoietic cell transplantation, with assessment up to one year. The registry definition requires an absolute neutrophil count (ANC) >500 cells /µL for 3 consecutive days and a platelet count >50,000 for one week without transfusion; stable engraftment is subsequently measured by the percentage of donor cells.

Engraftment is a clinically relevant transplant outcome because it indicates whether donor-derived blood-forming cells have become established. The specified blood-count criteria make the initial definition more explicit than a general judgment that a graft has taken. The subsequent donor-cell measure adds information about the origin of blood cells after transplantation. The record does not report how that later measure was incorporated into the endpoint assessment or how many participants met the full definition.

The endpoint is expressed as a count, not as a time-to-event measure or a continuous laboratory value. Interpreting a count requires knowing the number assessed and how participants with incomplete follow-up or unavailable measurements were handled. Those details, along with the observed primary endpoint count, are not reported in the registry record. The definition explains what the outcome was intended to capture; it is not itself evidence that stable engraftment occurred.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a count endpoint and lists no analyses. Statistical interpretation therefore begins by separating the outcome definition from an observed result: the definition is present, but the primary count and its uncertainty are not reported in the registry record. General statistical concepts can explain what would be needed to interpret such an outcome without implying that a particular method was used in this study.

What does a participant count represent?

A count of participants meeting an endpoint records how many people satisfy the stated criteria during the assessment period. To interpret it, a reader also needs the number eligible for assessment and the rules used for people whose outcome is unknown. A count alone does not show the proportion of the enrolled group unless its denominator is clear. The registry record gives enrollment as 6, but does not report the primary endpoint count, the assessed denominator, or how missing endpoint observations were handled.

For a binary outcome such as whether stable engraftment occurred, an estimate of the underlying event probability is uncertain, especially when the observed group is small. A confidence interval is a statistical range that communicates this uncertainty under an analysis model; it is not a guarantee about an individual outcome. No confidence interval for stable engraftment is reported in the registry record. Without an observed count and a defined analysis population, the precision of the primary result cannot be evaluated.

Why does the design matter?

The study is listed as single-group, with allocation not applicable and no masking. General interpretation of a single-group study focuses on outcomes observed among participants who received the study regimen. It does not provide a direct estimate of the contrast between that regimen and a concurrent comparator. A result from a separate group or another period could differ because of patient characteristics, clinical practice, follow-up, or other factors; those differences cannot be isolated by this design alone.

Masking concerns whether people involved in a study are kept unaware of treatment assignment. The registry lists masking as none. That design label does not establish whether outcome assessment was subjective or whether assessment was influenced by knowledge of treatment. The primary endpoint uses specified blood-count criteria, but the record does not describe adjudication, monitoring, or safeguards for outcome assessment.

What can the planning illustration tell readers?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect, and that non-time-to-event illustrations refer to participants per arm for 80% power; time-to-event illustrations refer to total events. These are planning assumptions, not the design features of this single-group study. The observed effect and resulting planning values are not reported in the registry record, so their practical implications cannot be evaluated from the record.

In general, a sample-size calculation estimates the amount of information needed to detect a specified effect under stated assumptions. It is not evidence that a study had a given probability of success after the outcomes were observed. The record explicitly characterizes its illustration as planning based on the observed effect, rather than the trial’s own design. Such planning values are not observed power, and they cannot compensate for a missing endpoint result or create a valid comparator in a single-group study.

How should uncertainty and event counts be read?

For rare or uncommon outcomes, a small study can produce estimates with considerable uncertainty. A confidence interval, when reported, helps show the range of values compatible with the data and model. A narrow interval generally indicates greater precision than a wide one, but neither width nor statistical significance alone determines clinical importance. No interval estimates or tests are listed among the analyses in the registry record.

Adverse-event percentages also require attention to their denominator and event definition. A participant can experience more than one event, and a single category may include multiple episodes. General interpretation therefore distinguishes the number of affected participants from the number of events. The registry record reports the group-level counts and selected serious-event terms, but does not clarify whether the term percentages count participants or episodes, or whether terms overlap. The figures are descriptive and should not be summed into an overall event rate.

The registry record lists 0 analyses. This means that no analysis is reported in the record; it does not establish what analyses may have been conducted outside it. The statistical analysis plan, any interim analyses, and the methods used to estimate the named survival outcomes are not reported in the registry record. No unreported model, adjustment, or inferential procedure should be assumed.

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("Mesenchymal Stromal Cells")
n      <- c(6)
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  Mesenchymal Stromal Cells  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record names a primary endpoint and several secondary outcomes, including overall survival and disease-free survival at six months and one year after transplantation. Considering several outcomes raises a general multiplicity issue: if many statistical tests are conducted, the chance of at least one apparently unusual result can increase. Researchers may prespecify one primary question, adjust for multiple testing, or treat secondary findings as exploratory. The registry record does not report a multiplicity strategy or any testing hierarchy.

There are no analysis results listed in the record, so it is not possible to determine whether any multiplicity adjustment was applied or how multiple outcomes were interpreted. The record also does not report interim analyses or stopping rules. These details should not be inferred from the phase, completion status, or number of outcomes.

Missing data can affect both counts and survival outcomes. For the primary endpoint, a participant with no assessable engraftment status could be classified in different ways depending on the prespecified analysis plan; each approach answers a different question and can produce different estimates. The registry record does not state how missing measurements, withdrawal, or incomplete follow-up were handled, nor does it report the number of participants assessed for each endpoint.

Analysis populations are also not described. For example, a record might specify whether analyses include everyone enrolled, only those who began treatment, or only those with an observed endpoint. The registry record does not report such population definitions. Because enrollment is 6, knowing the denominator and handling of each participant is important for understanding the reported counts. No such participant-level accounting is reported.

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

Serious events with the highest arm-level rate: graft failure with autologous recovery (33.3%), cmv viremia (33.3%), sos (16.7%), ebv-ptld (16.7%), grade ii gvhd (16.7%).

The registry lists 6 participants at risk for serious adverse events and 6 affected in the mesenchymal stromal cell group. For other adverse events, it lists 6 at risk and 0 affected. It also records 4 deaths. These figures are counts, not a comparison with another treatment group, and they do not by themselves establish the cause of any event or death.

The selected serious-event terms are graft failure with autologous recovery and CMV viremia, each recorded as 33.3%; SOS, EBV-PTLD, Grade II GVHD, and Grade III acute GVHD, each recorded as 16.7%. The registry record does not clarify whether these percentages describe participants or event episodes, whether one participant could appear under multiple terms, or the observation window for the listing. They should not be added together as if they were distinct groups.

Serious adverse events and other adverse events are separate registry categories. The zero count for other adverse events does not mean there were no serious events; the record lists all 6 participants as affected by serious adverse events. Details such as event onset, duration, severity beyond the listed terms, attribution, and causes of death are not reported in the registry record.

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

The record establishes that a completed, single-group phase 2 pilot enrolled 6 participants and planned to assess stable engraftment up to one year after transplantation. It also records serious adverse-event counts, selected serious-event terms, and deaths. These registry entries describe the registry entry; they do not establish that the transplantation approach achieved its stated aims or that any outcome was caused by the intervention.

The most important interpretive gap is the absence of a reported primary endpoint count. The endpoint definition is specific, but without the observed count and the number assessed, the frequency of stable engraftment cannot be determined. The secondary survival outcomes are named but their results are also not reported. Completion status is an administrative study status, not a clinical result.

The safety counts should be considered alongside the small enrollment and the lack of a comparator. They signal that serious events and deaths were recorded in the study group, but the registry does not provide sufficient detail to attribute these events, assess their timing, or compare their frequency with another strategy. The percentages for individual event terms likewise do not establish whether terms overlap or reflect distinct participants.

In general, an observed outcome in a single group cannot answer the counterfactual question of what would have happened to the same participants under a different approach. A controlled comparison can help estimate such a contrast, subject to its own design and assumptions. No controlled comparison is reported. The record therefore supports cautious description of the design and recorded safety information, but not a conclusion about comparative benefit, harm, or effectiveness.

14. Why This Trial Matters Statistically

This study is statistically notable because its central endpoint is explicitly defined while its observed result is absent from the registry record. The distinction matters: an endpoint definition tells readers what was intended to be measured, whereas an outcome count is needed to judge what was observed. Without that count, neither the event frequency nor its precision can be assessed.

The single-group design is another central feature. It allows outcomes among enrolled participants to be described, but offers no randomized comparison and no concurrent control group. The registry record marks allocation as not applicable and masking as none. These are important boundaries on what the data could establish, even if the primary outcome result were available.

The enrollment of 6 also makes transparent denominators especially important. In a small study, each participant can materially affect the observed count. Reporting the number assessed, the handling of missing outcomes, and individual event overlap would help readers understand how the group-level summaries were formed. Those details are not reported in the registry record.

Finally, the entry includes planning assumptions for sample-size illustrations, but describes them as based on the observed effect rather than the trial’s own design. They should not be confused with a prospective justification for this pilot or evidence that it had sufficient power. The statistical contribution of the record is therefore primarily descriptive: it identifies the question, operational endpoint, design constraints, and some safety counts, while leaving the main efficacy result and inferential analysis unavailable.

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 observed stable-engraftment count. It also does not provide the number assessed for that endpoint, participant-level follow-up, or the handling of unobserved outcomes. The endpoint definition alone cannot establish how many participants met it.

The study has no comparator and no random allocation, so the record cannot support a direct estimate of the difference between this regimen and another approach. The enrollment of 6 further limits the amount of information available for describing outcomes and safety. The listed counts should be understood as observations in this group, not stable estimates of outcomes in a broader population.

Secondary survival results are not reported, despite the outcomes being named. The record does not report the timing or causes of the 4 deaths, or how death was handled in the disease-free survival outcome. It also does not explain whether the serious-event percentages represent participants or episodes, whether event categories overlap, or the duration over which safety was assessed.

Other details relevant to interpretation are not reported in the registry record: the actual donor source for participants, detailed treatment delivery, the statistical analysis plan, analysis populations, missing-data methods, multiplicity handling, and interim analyses. The listed planning assumptions do not resolve these omissions and are not the trial’s own design justification. These limitations mean that the record supports a limited descriptive reading, rather than a complete assessment of efficacy, safety attribution, or comparative effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs — NCT00957931.
• Registry record last updated 2018-08-06; status last verified 2018-07.
• Results first posted 2018-08-06.
• 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

NCT00957931 is a completed phase 2, single-group pilot with enrollment of 6. It concerns hematopoietic cell transplantation for high-risk sickle cell disease and other non-malignant red blood cell disorders, with mesenchymal stromal cells listed as a co-treatment. Allocation is marked not applicable and masking is none.

The primary outcome is a count of participants with stable engraftment, assessed up to one year and defined using neutrophil and platelet criteria followed by donor-cell measurement. The observed primary outcome count is not reported in the registry record. Named secondary outcomes include overall survival and disease-free survival at six months and one year.

The safety listing records 6 of 6 participants affected by serious adverse events, 0 of 6 affected by other adverse events, and 4 deaths. No analyses are listed. The record does not report outcome estimates, uncertainty intervals, or a comparative treatment effect.