Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen (NCT02199041), a na phase 2 study. The primary outcome is Number of Participants With Neutrophil Engraftment.

2. Clinical Question

The primary objective was to estimate donor-derived neutrophil engraftment by day +42 after transplant in this clinical setting. This is an estimation question in a single-group Phase 2 study, not a randomized comparison of two transplant strategies. The registry also identifies secondary objectives concerning malignant relapse, event-free survival, and overall survival at one year, along with acute and chronic graft versus host disease, secondary graft failure, transplant-related mortality, and transplant-related morbidity during the first 100 days.

The record describes the intended population as participants with high-risk hematologic malignancies without the specified donor options. It does not provide the primary endpoint result, detailed participant characteristics, or an analysis population for that endpoint. Therefore, the registry record does not establish how many enrolled participants achieved engraftment by the target day, or how precisely that incidence was estimated.

3. Trial Design

This was a Phase 2, single-group study sponsored by St. Jude Children's Research Hospital. The registry lists an enrollment of 24 and a status of terminated. The study started on 2014-07-11, and primary completion is listed as 2017-05-23. The reason for termination is not reported in the registry record. Allocation is recorded as not applicable, and masking as none.

The treatment strategy combined T cell depleted haploidentical peripheral blood stem cells with an unrelated umbilical cord blood transplant after a total lymphoid irradiation-based preparative regimen. The treatment description lists cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, G-CSF, mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion were prepared using the CliniMACS System. These details describe the registered treatment; they do not establish how consistently each component was delivered to each participant.

Because this is a single-group study, its primary endpoint is an estimate of the observed engraftment count or incidence in the treated group, rather than a treatment effect relative to a concurrent randomized group. The record identifies no assigned comparator arm. The separate blood donor group in the adverse event information should not be interpreted as a control arm for clinical efficacy: the registry explicitly notes that the groups are not a like-for-like control comparison.

The stated primary endpoint concerns neutrophil engraftment through day +42. Secondary outcome descriptions include relapse, event-free survival, overall survival, acute and chronic graft versus host disease, secondary graft failure, transplant-related mortality, and transplant-related morbidity. The corresponding outcome results and analysis details are not reported in the registry record. In particular, the record does not describe an analysis plan, interim analyses, or a sample-size justification. The listed enrollment is not by itself evidence that the study achieved a prespecified statistical precision or power target.

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: The 12 enrolled blood donors did not undergo transplantation and are therefore not included in the results reported here.

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 Number of Participants With Neutrophil Engraftment, measured over Until day 42 post-transplant.

The primary endpoint is the number of participants with neutrophil engraftment by day +42 post-transplant. The definition requires an absolute neutrophil count of at least 0.5 x 10^9/L (500/mm^3) on three consecutive laboratory values taken on different days. The values may reflect recovery derived from either donor, and the engraftment date is defined as the date of the first of those three values. This operational definition sets a specific threshold, repetition requirement, and time point for classifying engraftment.

Neutrophil recovery is an early transplant outcome. Counting participants who meet a prespecified recovery definition by a fixed time allows the study to describe how often this milestone was reached in the enrolled treatment group. It does not, by itself, measure longer-term survival, relapse, graft-versus-host disease, or transplant-related morbidity. Those outcomes are listed separately as secondary outcomes, with distinct follow-up periods.

The registry record gives the endpoint definition and timeframe, but not the observed count of participants who met it. It also does not report an endpoint estimate, a confidence interval, or a denominator for the endpoint analysis. Consequently, the endpoint can be described conceptually, but its observed frequency and statistical precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary outcome is a participant count: the number meeting a defined neutrophil engraftment criterion by day +42. A count is a direct description of how many people satisfy a rule. When a count is interpreted as an incidence or proportion, the denominator matters as well: it should be clear which participants were eligible for assessment and had sufficient follow-up. The registry record gives an enrollment of 24 but does not report the number meeting the endpoint or the endpoint analysis denominator. Enrollment and endpoint-evaluable population are not necessarily interchangeable.

What does the endpoint definition do?

The definition requires an absolute neutrophil count of at least 0.5 x 10^9/L (500/mm^3) on three consecutive laboratory values obtained on different days. Requiring repeated values makes the outcome depend on sustained laboratory evidence rather than a single reading. The date is assigned to the first qualifying value in the consecutive sequence. The registry permits recovery derived from either donor. A clear definition supports consistent classification, but it does not tell the reader how many participants met the definition or how missing laboratory measurements were handled.

What can a single-group estimate show?

In a single-group study, an endpoint count or incidence describes outcomes in the group receiving the registered approach. It does not provide a randomized contrast with another transplant strategy. General statistical principle: a comparison group helps separate an intervention-associated difference from other differences between patients and their care. Without a randomized comparator, this record cannot estimate a randomized between-group treatment effect. The separate blood donor category in the adverse event data is not a like-for-like control comparison.

How should uncertainty be understood?

General statistical principle: an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval expresses a range of values compatible with the data and analysis under its assumptions; it does not guarantee that the true value lies within the interval. For a participant count or incidence, precision depends on both the number of observed events and the number of participants contributing to the estimate. The registry record does not report the primary endpoint estimate or an interval, so its precision cannot be assessed.

Why do analysis details matter?

For a time-limited endpoint, the analysis should make clear how participants who die, withdraw, have incomplete laboratory data, or otherwise lack assessment are treated. Different approaches can yield different interpretations of an endpoint. The registry record does not report endpoint-specific missing-data procedures, analysis populations, or an analysis plan. These details should not be inferred from the endpoint definition or the listed enrollment.

The secondary outcomes involve different concepts and follow-up periods. Relapse, event-free survival, and overall survival are listed at one year after transplantation; acute and chronic graft versus host disease are described during the first 100 days, as are secondary graft failure, transplant-related mortality, and morbidity. These outcomes are not interchangeable with the primary engraftment endpoint. The record lists the outcome measures but does not report their results, estimands, or detailed statistical methods.

What does the registry say about planning?

The registry record does not report a sample-size justification or statistical analysis plan. The stated enrollment of 24 should therefore be read as a registry enrollment figure, not as evidence that a particular power or precision target was met. General statistical principle: power is a design property tied to a specified effect, variability or event rate, significance level, and analysis method. A calculation based on an observed effect is a planning illustration and is not observed power; it cannot establish that the original study was adequately planned. The specific assumptions and output for a sample-size illustration are not reported in the registry record.

The record reports no analyses in its analysis information. That absence means no inferential results can be evaluated from the posted information: there are no reported hypothesis tests, adjusted estimates, or confidence intervals to interpret. It does not establish whether analyses were performed outside the registry. The sponsor's analysis, if recorded elsewhere, is not described in this record.

Finally, adverse event counts should be interpreted as descriptive safety information. General statistical principle: an event occurring after treatment is not automatically caused by treatment. Attribution requires clinical and analytic context, and group counts alone do not supply that evidence. Here, the registry lists affected participants and deaths for the treatment and blood donor groups, but does not provide a causal assessment or a valid comparative efficacy design using those groups.

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("Treatment")
n      <- c(12)
events <- c(11)
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  Treatment  12  11  91.7  61.5  99.8  64.6  98.5  64.0  98.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and multiple secondary outcomes. The primary outcome is the number of participants with neutrophil engraftment by day +42. Secondary outcomes concern relapse, event-free survival, overall survival, acute and chronic graft versus host disease, secondary graft failure, transplant-related mortality, and transplant-related morbidity. Testing or estimating many outcomes can raise multiplicity concerns, because repeated statistical tests may increase the chance of at least one apparently notable result. Whether and how that issue was addressed is not reported in the registry record.

The record does not report an analysis plan, a hierarchy among secondary outcomes, an adjustment for multiple comparisons, or interim analyses. No inferential analyses are reported. It is therefore not possible to determine which outcomes, if any, were treated as confirmatory, or how uncertainty was handled across outcomes. The secondary outcomes should be read as registered objectives, not as evidence of observed effects.

The registry gives an enrollment of 24 but does not state the number included in each outcome analysis. It does not report endpoint-specific denominators, missing-data rules, or how participants with incomplete follow-up were handled. These omissions matter for interpreting a count and its uncertainty, particularly for outcomes with specified follow-up periods. The reason for termination is also not reported in the registry record. No assumptions about why the study ended or how missing data were handled can be made from the listed status alone.

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: hypotension (8.3%), pericardial effusion (8.3%), thrombotic thrombocytopenic purpura (8.3%), fever without neutropenia (8.3%), weight loss (8.3%).

For the treatment group, the registry lists 12 participants at risk for serious adverse events and 5 affected. For other adverse events, it lists 12 at risk and 12 affected. The treatment group also has 6 deaths listed. For blood donors, 12 are listed at risk for serious adverse events and 0 affected; the other adverse event category lists 12 at risk and 0 affected, with 0 deaths. These are group-level counts, not evidence that events were caused by the transplant regimen.

The registry lists Hypotension, Pericardial Effusion, Thrombotic Thrombocytopenic Purpura, Fever without Neutropenia, Weight Loss, and Diarrhea among the serious adverse event terms, each at 8.3%. The record does not provide additional event-level context in the information reported, such as timing, severity beyond the serious-event classification, recurrence, or attribution. The percentages should not be treated as comparative risk estimates between treatment and blood donors.

The blood donor group is not a like-for-like control group, so its counts should not be used to estimate an intervention effect or to make a direct safety comparison. The registry record does not report a causal assessment of deaths or adverse events. These figures are descriptive safety information, and the small listed group sizes limit how broadly they can characterize risk.

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

The registry record establishes that the study was designed to estimate donor-derived neutrophil engraftment by day +42 after a combined haploidentical peripheral blood stem cell and unrelated umbilical cord blood transplant approach. It also specifies a laboratory definition for engraftment and lists several secondary outcomes. These are useful descriptions of what investigators intended to evaluate.

What the record does not establish is the observed primary outcome. The number of participants with neutrophil engraftment is not reported in the registry record, and neither an endpoint denominator nor a measure of precision is given. Accordingly, readers cannot assess the observed engraftment frequency from this information. The listed enrollment of 24 does not fill that gap.

The single-group design also means the study is not a randomized comparison against another transplant strategy. Even if an outcome estimate were available, it would describe this treated group and would not by itself show what would have happened under an alternative approach. The registry specifically notes that the blood donor group is not a like-for-like control comparison. Safety counts should likewise be read descriptively rather than as proof of treatment causation.

The secondary outcomes are named, but their results are not reported in the registry record. Therefore, this record does not establish results for relapse, event-free survival, overall survival, graft-versus-host disease, graft failure, transplant-related mortality, or morbidity. The study's terminated status does not explain the circumstances or determine the interpretation of its outcomes. Its reason for termination is not reported in the registry record.

In general, statistical estimates describe the data available under a study's design and analysis assumptions; they do not automatically establish causality or generalize beyond the studied population. Here, the missing endpoint results and analysis details make even the descriptive efficacy interpretation unavailable. The record can be used to understand the question and registered design, but not to draw a conclusion about the observed engraftment outcome or comparative treatment effects.

14. Why This Trial Matters Statistically

This study raises a design and measurement question in a specialized transplant setting: whether donor-derived neutrophil engraftment can be estimated by a defined early post-transplant time point after a combined graft approach and total lymphoid irradiation-based preparative regimen. The endpoint is stated with a laboratory threshold, a requirement for consecutive values, and a timing rule. Such definitions matter statistically because they determine how participants are classified and what an endpoint count represents.

The registry also illustrates the distinction between a study objective and a result. The primary objective is clearly stated, but its observed outcome is not reported in the registry record. Without the outcome count, denominator, and uncertainty, readers cannot evaluate the estimate the study set out to produce. An enrollment figure alone cannot answer the endpoint question or indicate how precise an estimate would be.

Design is equally important. A single-group Phase 2 study can characterize outcomes in the treated group, but it does not provide a randomized comparison with another strategy. That distinction is particularly important when interpreting clinical outcomes and safety counts. The blood donor group listed for adverse events is not a like-for-like control group, so its counts cannot supply the missing efficacy comparison.

Finally, multiple secondary objectives and safety summaries make transparent reporting of analysis populations, missing data, and uncertainty valuable. Those details are not reported in the registry record. The statistical lesson is not that the study's approach succeeded or failed, but that a carefully specified endpoint and a listed enrollment do not replace posted outcome estimates and their context.

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 central limitation for statistical interpretation is that the registry record does not report the primary endpoint result. It specifies the number of participants with neutrophil engraftment as the outcome but gives no count, endpoint denominator, incidence estimate, or confidence interval. The registered enrollment of 24 does not identify how many participants had evaluable laboratory follow-up through day +42.

The study is single-group and has no randomized comparator. This means the design cannot establish a randomized treatment effect relative to another transplant strategy. The registry notes that allocation is not applicable and that the blood donor group is not a like-for-like control comparison. The donor group should not be treated as an alternative clinical arm.

The record lists multiple secondary outcomes but does not report their results or analysis methods. It does not describe how missing outcomes were handled, how analysis populations were defined, whether outcomes were adjusted for multiplicity, or whether interim analyses occurred. The reason for the terminated status is not reported in the registry record. These missing details prevent evaluation of the completeness and uncertainty of the outcome evidence.

The safety information is also limited to group counts and selected serious adverse event terms. The record does not provide causal attribution, event timing, or enough context to use the blood donor group as a comparison. These counts therefore describe the registry's safety summaries, rather than demonstrating the cause of events or deaths. The stated enrollment and outcome objectives should not be mistaken for a complete statistical report of the trial's results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen — NCT02199041.
• Registry record last updated 2018-02-07; status last verified 2017-08.
• Results first posted 2018-02-07.
• 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

NCT02199041 is a Phase 2, single-group study of a combined T cell depleted haploidentical peripheral blood stem cell and unrelated umbilical cord blood transplant approach using a total lymphoid irradiation-based preparative regimen. The registry lists an enrollment of 24, status as terminated, a start date of 2014-07-11, and primary completion on 2017-05-23. The reason for termination is not reported in the registry record.

The primary outcome is the number of participants with neutrophil engraftment by day +42, defined by an absolute neutrophil count of at least 0.5 x 10^9/L (500/mm^3) for three consecutive laboratory values on different days. The endpoint result is not reported in the registry record. Secondary outcomes include relapse, event-free survival, overall survival, graft-versus-host disease, secondary graft failure, transplant-related mortality, and transplant-related morbidity; their results are also not reported.

Safety data list 5 of 12 treatment-group participants affected by serious adverse events, 12 of 12 affected by other adverse events, and 6 deaths. The corresponding blood donor counts are 0 of 12, 0 of 12, and 0 deaths. The registry states that these groups are not a like-for-like control comparison.