HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies (NCT00145626), a na phase 2 study. The primary outcome is One-year Survival.

2. Clinical Question

The study asked whether infants with high-risk hematologic malignancies who received a haploidentical transplant regimen would be alive one year after transplantation. The treatment approach combined a conditioning regimen that excluded total body irradiation, a T-cell-depleted stem cell graft from an HLA-nonidentical family donor, and a later infusion of donor natural killer cells. The registry describes the aim as evaluating one-year survival; it does not report the numerical survival estimate.

This is a question about outcomes after a treatment strategy in a selected group, rather than a direct test of whether the strategy is better than a specific alternative. Without a comparator, any survival estimate would describe the observed study group and would not, on its own, isolate the treatment's effect from other explanations.

3. Trial Design

The registry lists this as a Phase 2, single-group study with no masking and no allocation to comparative arms. Its status is completed. The listed enrollment is 40; the record does not clarify in the primary-outcome entry how many participants contributed to the survival analysis. The study began in 2004-05 and had a primary completion date of 2015-03.

The intervention centered on allogeneic stem cell transplantation using cells from an HLA-nonidentical family donor. The registry describes donor cells as depleted of T lymphocytes ex vivo using the CliniMACS CD34+ selection system. It also describes an infusion of donor natural killer cells after transplant, purified using a CliniMACS process. Chemotherapy and antibodies are listed among the interventions, along with the device and transplantation procedure.

There is one arm, called Study Participants. This design can describe outcomes among participants who received the study treatment, but it does not create a contemporaneous control group. Because allocation is listed as not applicable, treatment assignment was not randomized between study arms. The registry's stated objective is to evaluate one-year survival in infants with high-risk hematologic malignancies receiving the treatment strategy.

The listed secondary outcomes cover transplant-related adverse outcomes, including regimen-related mortality, engraftment failure, fatal acute graft-versus-host disease, and chronic graft-versus-host disease. Other secondary outcomes concern factors that may relate to one-year survival, including donor age, CD34 dose, natural killer cell dose, and disease status at transplantation. The registry record does not report results for these outcomes in the registry record for this analysis, nor does it describe how the factor analyses were conducted.

The study's single-group structure is central to interpreting its evidence. It can document outcomes in the treated group, but cannot directly compare those outcomes against an untreated group or a different transplant strategy. Its findings would also pertain to the selected population enrolled in the study, not automatically to every child with a hematologic malignancy.

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: 19 stem cell recipients were enrolled, and 5 were excluded. Two participants did not have natural killer cell infusions due to donor was unable to donate enough CD34+ cells or CD56+ cells for infusion, 1 participant became ineligible because they turned 2 years old prior to start of therapy, 1 withdrew and 1 expired.

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.

Population: All evaluable participants are included.

6. Primary Endpoint

The registry lists the primary outcome as One-year Survival, measured over One year after transplant.

The primary endpoint is one-year survival after transplant, expressed as a percentage of participants. In the registry's description, this is the Kaplan-Meier estimate of survival one year after transplantation for infants with high-risk hematologic malignancies receiving the specified transplant regimen and subsequent donor natural killer cell infusion. The registry record does not report the estimate itself.

Survival is a time-to-event outcome: the event of interest is death, and the analysis considers how long participants remain alive after the defined starting point. A Kaplan-Meier estimate is commonly used for this kind of outcome because it can incorporate follow-up that ends at different times. Participants whose later survival status is not observed may contribute information up to the time they were last known to be alive, under the method's assumptions. General explanation: this approach depends on appropriate handling of incomplete follow-up; the registry does not report the details of follow-up or censoring for this analysis.

A one-year time point makes the endpoint clinically interpretable as survival at a specified interval after transplant. It does not, by itself, explain why survival may differ among participants or establish that the treatment caused an observed outcome. In a single-group study, the estimate would describe survival in the treated cohort. Comparison with another strategy would require suitable comparative evidence, which this registry design does not supply.

The endpoint description names a Kaplan-Meier estimate but does not state a confidence interval or other measure of uncertainty, and no numerical survival result is reported in the registry record. Consequently, the precision of the one-year estimate cannot be assessed from the record information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group Phase 2 study and identifies one-year survival as its primary endpoint. The primary outcome is described as a Kaplan-Meier estimate. That information indicates the broad endpoint and method, but it does not give a complete statistical analysis plan. Details such as the survival analysis population, censoring rules, confidence interval method, or handling of incomplete records are not reported in the registry record.

What does a Kaplan-Meier estimate represent?

General explanation: the Kaplan-Meier method estimates the probability of remaining free of an event over time. For a survival endpoint, the event is death. The method uses the observed event times and accommodates participants whose follow-up ends before the study's final observation time. Those participants are generally censored at the point their outcome is no longer known: their observed follow-up contributes information up to that point, but their later status is not assumed to be known.

A survival estimate at a specified time point, such as one year, is read from the estimated survival curve. It is not necessarily the same as a simple count of participants known to be alive at that time divided by the total enrolled. That distinction can matter when participants have different follow-up durations or incomplete follow-up. The registry record does not state how many participants were censored, when follow-up ended for participants, or what rules were applied.

Why does uncertainty matter?

General explanation: a point estimate summarizes the data, while a confidence interval conveys statistical uncertainty around that estimate under the chosen analysis assumptions. A narrower interval indicates greater precision than a wider interval. The registry description names the Kaplan-Meier estimate but does not report the one-year estimate or its confidence interval. Without those results, neither the estimated survival level nor its precision can be assessed.

Precision depends on the amount and timing of observed follow-up and events, not only on the enrollment figure. The record lists enrollment as 40, but does not report the number included in the primary analysis or the number with outcome information at one year. It would therefore be inappropriate to infer precision from enrollment alone.

What can a single-group design establish?

General explanation: a single-group study can describe the outcomes observed among people who receive a treatment. It does not directly estimate the contrast between that treatment and an alternative, because no concurrent comparison group is present. In this study, allocation is recorded as not applicable and the model as single group. Thus, the design does not support a randomized between-group treatment-effect estimate.

Any observed survival would be influenced by the characteristics of the participants, the disease and its status, other aspects of care, and follow-up. Without a comparator, these influences cannot be separated from the effect of the treatment strategy by a direct randomized contrast. The registry also describes several treatment components, so an outcome cannot be attributed to a specific component from this design alone.

What is not specified about the analysis?

The registry record does not report the statistical plan in enough detail to determine the method used for confidence intervals, whether any adjusted analyses were planned, how incomplete follow-up was handled, or which analysis population was used. It does not report interim analyses or a sample-size justification. These omissions should not be filled by assuming customary procedures; different choices can affect how an estimate is calculated and interpreted.

The primary outcome is a time-to-event endpoint, while several named secondary outcomes concern event counts or percentages. General explanation: a binary event outcome can be summarized by the number or proportion of participants with the event, whereas a time-to-event analysis uses event timing and follow-up information. The registry identifies the primary endpoint as a percentage and also describes a Kaplan-Meier estimate. Since no numerical outcome result is available, there is no reported estimate to recalculate or compare with another summary.

How should safety percentages be read?

General explanation: a percentage is interpretable only in relation to its denominator, event definition, and observation period. A percentage can refer to participants with at least one event, reports of events, or another registry-defined quantity. The serious adverse event terms are listed with percentages, but the registry entries available do not specify the denominator or reporting convention for those percentages. They should therefore be read as registry-listed values, not as fully defined estimates of risk.

The safety fields separately report participants at risk and affected for serious and other adverse event groupings. Those counts do not supply the missing primary survival estimate. They also do not by themselves explain event severity, timing, recurrence, or attribution to the treatment. The registry lists several adverse event terms, but a list of terms and percentages is not a comparative safety analysis.

Finally, statistical results need to be read alongside study design and reporting completeness. Here, the record establishes the endpoint definition and general analysis approach, but does not report the survival estimate, its uncertainty, or key implementation details. No numerical conclusion about one-year survival or comparative treatment effects can be drawn from the endpoint description alone.

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("Study Participants")
n      <- c(14)
events <- c(7)
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  Study Participants  14  7  50.0  23.0  77.0  26.8  73.2  26.6  73.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures and 1 analysis. The primary outcome is one-year survival, and the named secondary outcomes include transplant-related adverse outcomes and factors that may affect one-year survival. The record does not describe a strategy for controlling the risk of false-positive findings when multiple outcomes or analyses are considered. It also does not identify a hierarchy among the secondary outcomes or explain how their results would be interpreted together.

General explanation: when multiple hypotheses are tested, the chance of at least one apparently noteworthy result can increase. Statistical approaches can address this issue, but the appropriate approach depends on the analysis plan and study aims. Since that plan is not reported in the registry record, it is not possible to determine whether any adjustment was used or intended. The registry entries also do not provide numerical secondary-outcome results to evaluate.

Missing-data details are not reported in the registry record. For the survival endpoint, the description names a Kaplan-Meier estimate, but does not describe follow-up completeness, censoring, or the number of participants contributing data at the one-year time point. These details affect interpretation of the estimate and its precision. The record does not state whether missing outcome information was addressed through additional analyses.

The analysis population is also not specified in the registry record. Although the registry lists enrollment as 40, it does not say how many participants were included in the primary analysis or whether all enrolled participants were analyzed. Consequently, the relationship between the enrollment figure and any outcome denominator cannot be determined. The registry record does not report a sample-size justification or interim analyses.

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: fever without neutropenia (56.2%), graft rejection (18.8%), hypoxia (18.8%), infection, staphylococcus aureus, blood (12.5%), seizure (12.5%).

The safety fields list 16 participants at risk and 15 affected for the serious adverse event grouping, and 16 participants at risk and 16 affected for the other adverse event grouping. These are registry-reported counts for the safety fields; they should not be added together or treated as the number analyzed for the primary survival outcome. The registry record does not explain the relationship between these safety denominators and the enrollment figure.

The registry also lists serious adverse event terms with percentages: fever without neutropenia, 56.2%; graft rejection, 18.8%; hypoxia, 18.8%; infection, Staphylococcus aureus, blood, 12.5%; seizure, 12.5%; and engraftment syndrome, 12.5%. The denominator and reporting convention for these percentages are not reported in the registry record. Without that information, the values should not be interpreted as directly comparable risks or as percentages of all enrolled participants.

These entries do not establish when events occurred, whether participants had more than one event, how events were attributed, or how long participants were followed for safety. The registry lists secondary outcomes concerning transplant-related mortality, engraftment failure, and graft-versus-host disease, but numerical results for those outcomes are not reported in the registry record. Safety entries are separate from the primary one-year survival result, which is also not reported in the registry record.

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

The record describes a study of a complex transplant strategy in infants with high-risk hematologic malignancies. Its primary question concerns survival one year after transplant, estimated using the Kaplan-Meier method. However, the numerical one-year survival result is not reported in the registry record. The record therefore does not allow readers to determine the observed survival estimate or its precision.

Even if a numerical estimate were available, this single-group study would describe outcomes among participants treated with the study strategy rather than provide a direct comparison with another approach. There is no randomized control group in the design. Accordingly, this study alone could not establish how outcomes would have differed under another treatment or isolate the causal contribution of the transplant regimen.

The intervention involves multiple components, including chemotherapy and antibodies, allogeneic stem cell transplantation with a T-cell-depleted graft, and a donor natural killer cell infusion. A single-group outcome would reflect the combined treatment and the circumstances of care; it could not determine which component accounted for an observed outcome. Nor would the study design establish that the same result would occur in a different patient group or setting.

The registry's listed enrollment is 40, but the primary analysis population and follow-up completeness are not reported in the registry record. The record also does not provide the confidence interval for the primary estimate. These gaps prevent assessment of the number contributing to the endpoint and the statistical uncertainty around it. Enrollment alone cannot substitute for these details.

Safety entries include participant counts and a list of serious adverse event terms with percentages. These entries are not a substitute for a full account of the primary endpoint or a comparative safety analysis. The denominator for the listed percentages and details about timing, recurrence, and attribution are not reported in the registry record.

The study's stated objective and outcome definitions make clear what it set out to assess. They do not demonstrate a particular survival outcome, a treatment benefit, or an absence of adverse outcomes. A result should be interpreted only when the registry reports the relevant estimate and its uncertainty, with due regard to the single-group design and incomplete analysis details.

14. Why This Trial Matters Statistically

This trial addresses a difficult statistical setting: an uncommon, serious disease population and a complex treatment strategy evaluated in a single group. The registry record identifies the target population, intervention, and one-year survival question, giving readers a framework for understanding what the investigators intended to assess. It also makes clear that the design is not a randomized comparison.

That distinction is important when interpreting outcomes. In a single-group study, observed survival can describe the experience of participants receiving the regimen, but it cannot directly show how that experience compares with another strategy. This matters especially when the treatment includes several elements, since the design does not isolate the effect of any one component.

The study also illustrates why reporting the endpoint definition is not enough to interpret a result. The registry specifies a Kaplan-Meier estimate for one-year survival, but the numerical estimate and its uncertainty are not reported in the registry record. Without those results, the intended statistical approach cannot answer the clinical question for readers. Reporting the analysis population and follow-up details would also help readers understand the basis and precision of an estimate.

Safety summaries require similar care. Counts and event-term percentages can be informative only when their denominators, definitions, and observation periods are clear. Here, the record includes safety counts and terms, but does not provide all information needed to interpret the listed percentages as defined risks.

Statistically, the study's value lies in the question it was designed to examine and the treatment setting it documents. Its evidential limits are equally important: no comparator, no reported primary survival estimate, and no complete account of analysis details in the registry record. Keeping those strengths and limits separate prevents an endpoint description or safety listing from being mistaken for a comparative treatment conclusion.

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 interpreting outcomes is that the registry record does not report the one-year survival estimate, even though survival is named as the primary endpoint and a Kaplan-Meier method is specified. It also does not report a confidence interval or other measure of precision. The outcome itself therefore cannot be described quantitatively in the registry record.

The study is listed as single group, with allocation not applicable and no masking. There is no concurrent control group in the registry design. Any outcome among the treated participants would be descriptive rather than a randomized estimate of the difference between treatment strategies. The design also cannot separate the contributions of chemotherapy and antibodies, transplantation, graft processing, and natural killer cell infusion.

The registry lists enrollment as 40, but does not report the primary analysis population or the number with relevant follow-up. It does not provide details about censoring, missing outcome information, follow-up duration beyond the endpoint definition, or the method used to quantify uncertainty. The sample-size justification and interim analysis details are not reported in the registry record.

The record names multiple secondary outcomes, but the registry entries available do not include their numerical results or describe how multiplicity was handled. Safety percentages are listed without a stated denominator or reporting convention. The safety fields do not fully describe event timing, recurrence, or attribution.

These limitations are specific to interpreting this registry information. They do not establish that an analysis was not performed; they mean that the relevant details are not reported in the registry record. The registry entries also do not allow conclusions about generalizability beyond the selected study population.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies — NCT00145626.
• Registry record last updated 2017-06-19; status last verified 2017-05.
• Results first posted 2015-12-14.
• 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 lists NCT00145626 as a completed Phase 2, single-group study with enrollment of 40. It concerns haploidentical stem cell transplantation and donor natural killer cell infusion for infants with high-risk hematologic malignancies. The primary endpoint is one-year survival after transplant, described as a Kaplan-Meier estimate.

The registry does not report the numerical primary survival estimate or its precision in the registry record. The design has no randomized comparator, and the primary analysis population and follow-up details are not specified. Safety fields list affected-participant counts and serious adverse event terms with percentages, but the denominator for those percentages is not reported in the registry record.