Allogeneic Hematopoietic Stem Cell Transplantation With Reduced Intensity Pre-transplant Conditioning for the Treatment of High-risk Hematological Malignancies (V3): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Allogeneic Hematopoietic Stem Cell Transplantation With Reduced Intensity Pre-transplant Conditioning for the Treatment of High-risk Hematological Malignancies (V3) (NCT01139164), a na phase 2 study. The primary outcome is To Determine the Treatment-related Mortality Rate of Allogeneic Stem Cell Transplants Using Reduced-intensity Conditioning Regimens Within 1st 100-days..

2. Clinical Question

The clinical question is therefore descriptive: what treatment-related mortality was recorded among participants receiving transplantation with these conditioning regimens? Because regimens were assigned according to diagnosis and there was no randomized control group, the study design does not isolate the effect of reduced-intensity conditioning from differences in diagnosis, regimen, or other participant characteristics. The registry also identifies engraftment and transplant morbidity as secondary outcome topics, but does not provide numerical findings for them in the posted record.

3. Trial Design

The registry describes a phase 2, single-group, non-randomized study sponsored by the Medical University of South Carolina. It lists 78 enrolled participants and three drug intervention labels: Regimen A, Regimen B, and Regimen C. The brief summary says patients were assigned to one of the three regimens depending on diagnosis. Although the registry presents regimen groups, it does not describe a randomized allocation process or a like-for-like control comparison; allocation is marked not applicable.

The study concerns allogeneic hematopoietic stem cell transplantation with reduced-intensity pre-transplant conditioning for high-risk hematological malignancies. The registry lists the start as 2010-06, primary completion as 2014-09, and status as terminated. It does not report why the study was terminated. The listed dates describe the registry record and do not establish the duration of follow-up for each participant.

The brief description states that follow-up was intended to continue for the remainder of each patient’s life. It describes daily visits to the transplant team initially, followed by frequent visits for up to 6 months, with later visits adjusted according to the patient’s condition. These statements describe the planned follow-up approach in the brief summary; actual attendance, completeness of follow-up, and follow-up duration by participant are not reported in the registry record.

The primary outcome concerns the number of deaths before day 100. The registry also lists engraftment rate and morbidity as secondary outcome topics. It reports three outcome measures overall but does not provide their full numerical results in the posted record. No analysis results are listed. The registry record does not report the statistical analysis plan, a sample-size justification, or the reason the study ended.

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: For regimen B, only the subjects who participated in study intervention were analyzed for outcome measures.

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: Subjects who were enrolled to the study.

6. Primary Endpoint

The registry lists the primary outcome as To Determine the Treatment-related Mortality Rate of Allogeneic Stem Cell Transplants Using Reduced-intensity Conditioning Regimens Within 1st 100-days., measured over 8 years.

The primary endpoint is titled as the treatment-related mortality rate for allogeneic stem cell transplantation using reduced-intensity conditioning within the first 100 days. Its measure is the number of subject deaths prior to day 100, with participants as the unit. This is a binary-outcome framing at the participant level: a participant either has the specified event within the stated period or does not. The registry describes the measure as a count rather than giving a rate estimate or a time-to-event analysis.

Early mortality is a clinically relevant outcome in a transplantation study because it captures deaths occurring soon after treatment. That is a general explanation of why an early mortality endpoint may be used, not a claim about the trial’s findings. The registry record does not provide a numerical count, an estimated rate, a confidence interval, or a comparison for this primary outcome.

There is a reporting mismatch within the registry: the endpoint title and description specify deaths before day 100, but the timeframe field says 8 years. The record does not explain whether the longer timeframe applies to another aspect of outcome collection or is an entry error. The intended primary measure is therefore best described using its title and explicit measure description, while noting that the timeframe field is inconsistent. The population description also says that, for Regimen B, only participants who took part in the study intervention were analyzed for outcome measures. Further details on the analysis population are not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with identifying the design and the quantity the endpoint is intended to measure. This registry describes a phase 2, single-group, non-randomized study. Its primary measure is the number of participants who died before day 100, rather than a comparison between randomized groups. Counts can describe how many events were recorded in a defined group, but interpretation of a count also depends on the group being analyzed, event ascertainment, and the period over which participants were observed.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified analysis. A point estimate alone does not show how precise an estimate is. For a binary outcome, an analysis might report an event proportion with a confidence interval, but the registry record does not provide such an estimate for the primary endpoint. No confidence interval can be inferred from the posted primary outcome information.

Why does the study design matter?

Random allocation is a design method intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. This study is not described as randomized. The brief summary says the regimen depended on diagnosis, so clinical differences across regimen groups may be linked to the treatment assignment. Consequently, differences in their observed outcomes would not establish that the regimen itself caused the differences. The registry explicitly cautions that the arms are not a like-for-like control comparison.

For a non-randomized study, descriptive reporting can still characterize observed events in the enrolled group. It cannot, without additional assumptions and suitable analyses, separate the contribution of treatment from differences in who received each regimen. The registry record does not report adjusted estimates, the covariates that might have been considered, or an analysis plan. No claim about confounding adjustment can therefore be made.

How should the endpoint’s time period be read?

The primary outcome title and description specify deaths before day 100. The separate timeframe entry says 8 years. These entries do not align, and the registry does not explain the discrepancy. A time period matters because an event count depends on when events are considered eligible for inclusion. The explicit definition points to the first 100 days, but the inconsistency should remain visible rather than being silently resolved. The record also does not report participant-level follow-up or whether all participants had complete ascertainment through the endpoint period.

What do the adverse-event counts represent?

For Regimen A, the record lists 4 participants at risk and 0 affected by serious adverse events. For Regimen B, it lists 67 at risk and 32 affected. For Regimen C, it lists 7 at risk and 0 affected. These are counts as recorded for the groups, not estimates from a comparative model. The record gives no confidence intervals or inferential tests for these counts. A zero count in a group does not demonstrate that the underlying risk is zero; in general, event estimates based on limited observations can remain uncertain even when no events are observed.

The listed percentages for specific serious adverse-event terms are descriptive. The record does not specify the denominator for those percentages in the posted information, or whether terms can overlap for one participant. These percentages should therefore be read as registry-reported term frequencies, not as a partition of all adverse events.

What does over-dispersion mean in general?

Over-dispersion is a general issue in count-data analysis. It occurs when observed variability is greater than a model’s assumptions allow, which can make standard errors too small if the model is not suitable. It can matter when analyzing recurrent event counts or other count outcomes. The registry record does not report a count model, recurrent-event analysis, or an over-dispersion assessment, so this concept cannot be tied to a specific analysis in this study.

What can planning calculations establish?

Sample-size planning calculations are illustrations of how many participants might be needed under stated assumptions; they are not observed outcomes and are not observed power. The record’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a fraction of an observed effect. The record does not report the study’s own sample-size justification. Because the study itself is single-group and non-randomized, those generic two-arm planning assumptions should not be mistaken for the trial design. No planning values are stated in the registry information.

Recalculated results, when available, are simple unadjusted calculations from posted summary statistics and are not substitutes for a sponsor’s analysis. The registry record does not list analyses for the primary outcome, so there is no sponsor analysis or recalculated estimate to compare in this case.

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("Group 1: Regimen A", "Group 2: Regimen B", "Group 3: Regimen C")
n      <- c(4, 65, 7)
events <- c(0, 18, 0)
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  Group 1: Regimen A  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Group 2: Regimen B  65  18  27.7  17.3  40.2  18.3  39.6  18.3  39.6
ARM  Group 3: Regimen C  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome concerning treatment-related mortality and secondary outcome topics concerning engraftment and transplant morbidity. It reports three outcome measures overall but does not provide numerical results for those measures in the posted record. The registry record does not report whether a formal multiplicity procedure was used, how outcome families were defined, or whether any outcomes were designated as exploratory. When several outcomes are examined, multiplicity can increase the chance of at least one apparently notable finding by chance; whether and how that issue was addressed is not reported.

The record lists no analysis results. It does not report an interim analysis plan, stopping boundaries, or whether any interim efficacy or safety review took place. The study status is terminated, but the reason for termination is not reported. Termination alone does not establish that a particular safety, efficacy, or operational issue occurred.

Missing-data handling is also not reported. The brief summary describes intended follow-up, including visits initially and continued follow-up for the remainder of a participant’s life, but it does not give actual follow-up completeness or explain how unavailable outcome information was handled. The record does not state whether participants lost to follow-up were excluded, counted, or handled through another method.

The population description specifies that, for Regimen B, only subjects who participated in the study intervention were analyzed for outcome measures. The registry does not further explain the analysis population for the other regimens, the number excluded from any analysis, or the treatment of participants who did not receive intervention. These omissions limit assessment of whether the reported counts use consistent analysis populations across the regimen groups.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: gvhd (22.4%), respiratory failure (3.0%), respiratory arrest (3.0%), gastrointestinal hemorrhage (3.0%), nausea (3.0%).

The registry lists serious adverse-event counts by regimen group. Regimen A has 4 participants at risk and 0 affected; Regimen B has 67 at risk and 32 affected; Regimen C has 7 at risk and 0 affected. The listed count for other adverse events is 0 affected in each group, with the same group-specific numbers at risk. These are descriptive counts, not estimates from a randomized comparison.

The specific serious adverse-event terms reported include GVHD at 22.4%, respiratory failure at 3.0%, respiratory arrest at 3.0%, gastrointestinal hemorrhage at 3.0%, nausea at 3.0%, and altered mental status at 1.5%. The registry does not report the denominator used for these percentages in the posted information. It also does not say whether an individual could be included under multiple terms, so the listed percentages should not be summed or treated as distinct shares of participants.

In general, adverse-event counts describe events recorded under the study’s reporting procedures; they do not alone establish that an intervention caused an event. The registry information does not give event timing, severity details beyond the serious-event classification, exposure duration by regimen, or comparative safety analyses. The counts should therefore be read as recorded safety information, without treating differences between these non-randomized groups as causal evidence.

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

The registry record establishes that a phase 2, non-randomized study of reduced-intensity conditioning before allogeneic hematopoietic stem cell transplantation enrolled 78 participants. It identifies three regimens and a primary outcome intended to count deaths before day 100. It also provides selected serious adverse-event counts and term percentages. These details describe the study and some reported safety information, but they do not amount to a complete statistical account of the primary outcome.

The primary death count and an estimated treatment-related mortality rate are not reported in the registry record. There is no reported confidence interval, test result, or comparative estimate for the primary endpoint. Therefore, the posted record cannot show how precisely the primary outcome was estimated or whether it differed from a reference value or another treatment. Missing numerical results should not be interpreted as zero events or as evidence of a favorable or unfavorable outcome.

The regimen groups do not serve as randomized controls. Since the brief description says regimen assignment depended on diagnosis, the groups may differ for reasons related to diagnosis and treatment selection. Even if outcome counts differ between groups, the record does not support attributing those differences to the regimen alone. The adverse-event counts are descriptive and should be interpreted in that same design context.

The registry’s endpoint timeframe entry also conflicts with its title and measure description: the latter specify the first 100 days, while the timeframe field says 8 years. The record does not resolve that discrepancy. Likewise, the status is terminated without a reported reason, and the available information does not explain whether follow-up or analyses were incomplete.

In general, statistical evidence needs both an estimate and information about its uncertainty, along with a design capable of supporting the intended comparison. For this study, the posted information supports a cautious description of design and selected event counts. It does not establish the size, precision, or causal meaning of the primary mortality outcome.

14. Why This Trial Matters Statistically

This study illustrates why design labels and analysis populations matter when interpreting clinical outcomes. The registry describes a single-group, non-randomized study while also listing three regimen groups. Those groups are not equivalent to randomized treatment arms: the brief summary says regimen assignment depended on diagnosis. Recognizing that distinction prevents descriptive group differences from being mistaken for causal treatment effects.

The endpoint definition also demonstrates the importance of checking consistency across registry entries. The title and measure description focus on deaths before day 100, while the timeframe field reports 8 years. Because the record does not explain the mismatch, the intended endpoint period cannot be reconciled with certainty from the posted information alone. Precise endpoint definitions are essential for interpreting event counts and deciding which observations belong in an analysis.

The record also separates study registration details from analyzable results. It lists enrollment, regimen-specific serious adverse-event counts, and selected adverse-event term percentages, but no primary outcome analysis. A reader cannot infer the treatment-related mortality result from enrollment or safety counts. This is a useful reminder that a registered outcome is not the same as a reported outcome estimate.

Finally, the population statement for Regimen B narrows the described analysis group to subjects who participated in the intervention, while comparable details for the other groups are not given. Clear reporting of analysis populations, missing data, and follow-up is necessary to judge how well observed counts represent all enrolled participants. These reporting issues are not merely administrative: they define what the statistics can and cannot support.

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 main trial-specific limitation is the absence of numerical primary outcome results in the registry record. Although treatment-related mortality before day 100 is identified as the primary measure, no death count, rate estimate, confidence interval, or analysis result is reported. The primary outcome therefore cannot be assessed for magnitude or precision from the posted information.

The study is non-randomized and single-group, with regimen assignment described as dependent on diagnosis. The regimen groups are not like-for-like control groups, and the record does not report adjusted analyses that might address differences between them. The group-specific adverse-event counts should not be interpreted as causal treatment comparisons.

The endpoint timeframe is internally inconsistent: the outcome title and description specify the first 100 days, but the timeframe field says 8 years. The registry does not explain this discrepancy. It also does not report the reason for termination, detailed eligibility criteria, participant characteristics by regimen, actual follow-up completeness, or how missing outcome data were handled.

For Regimen B, the population description says only participants who took part in the intervention were analyzed for outcome measures. Equivalent analysis-population details for Regimens A and C are not stated. The record also does not provide event timing or a denominator for the listed serious adverse-event term percentages. These reporting gaps constrain interpretation of both the endpoint and safety information.

Finally, the registry lists secondary outcome topics but no analysis results, and it does not report a statistical plan, multiplicity approach, interim analyses, or a sample-size justification. The termination status cannot, by itself, explain whether these omissions reflect incomplete reporting or another circumstance.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Allogeneic Hematopoietic Stem Cell Transplantation With Reduced Intensity Pre-transplant Conditioning for the Treatment of High-risk Hematological Malignancies (V3) — NCT01139164.
• Registry record last updated 2018-07-11; status last verified 2016-02.
• Results first posted 2016-03-10.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a phase 2, single-group, non-randomized study of allogeneic hematopoietic stem cell transplantation with reduced-intensity pre-transplant conditioning for high-risk hematological malignancies. It lists 78 participants enrolled and three regimens, with assignment described as dependent on diagnosis. The sponsor is the Medical University of South Carolina. The record lists the study start as 2010-06, primary completion as 2014-09, and status as terminated.

The primary outcome is the number of deaths before day 100, although its timeframe field says 8 years. The record does not provide a numerical primary outcome result or analysis. It lists engraftment and morbidity as secondary outcome topics and reports selected serious adverse-event counts and term percentages. The reason for termination, analysis plan, missing-data methods, and detailed analysis populations are not reported in the registry record.