Blood Stem Cell Transplantation for the Treatment of Older Patients With Acute Myelogenous Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Blood Stem Cell Transplantation for the Treatment of Older Patients With Acute Myelogenous Leukemia (NCT00623935), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Relapse Free Survival at 1 Year.

2. Clinical Question

3. Trial Design

This is a Phase 2, non-randomized, single-group study with no masking. The registry record lists 56 enrolled patients and a completed study. The recorded start was 2007-03, and primary completion was 2013-06. The sponsor is University of Michigan Rogel Cancer Center. These design details describe the registered study; they do not supply evidence about the size or precision of the primary outcome.

The study concerns hematopoietic stem cell transplantation for older patients with AML. Its primary objective describes patients older than 55 years in CR or PR undergoing a 7-8/8 HLA-matched unrelated donor transplant. The regimen descriptions distinguish between remission groups: patients in CR were assigned FluBu2, described as reduced intensity, while patients in PR were assigned FluBu4, described as full intensity. The registry does not report the numbers treated in each remission group or clarify how the differing regimen descriptions relate to the primary objective's wording about a reduced-intensity regimen.

The record states that 54 patients were treated. One died before transplant, and one did not undergo transplant. Four patients were inevaluable for the primary outcome: three were less than one year post-transplant when the abstract was written, and one failed to engraft. These statements describe who contributed to endpoint evaluation, but they do not establish the complete analysis population or the handling of each person's follow-up in an outcome estimate.

Because allocation was not randomized and there is no like-for-like control comparison, the study is best read as an assessment of outcomes within a treated group, not as a randomized estimate of comparative treatment effect. The registry record does not report a detailed statistical analysis plan or the actual primary outcome result.

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: 56 patients were enrolled. 54 patients were treated (one died prior to transplant, one did not undergo a transplant) and 4 patients were inevaluable (3 patients were less than 1 year post transplant at the time the abstract was written and 1 failed to engraft).

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 Percentage of Participants With Relapse Free Survival at 1 Year, measured over 1 year.

The primary endpoint is the percentage of participants with relapse-free survival at one year. Relapse-free survival is a time-related outcome intended to reflect remaining alive without relapse over a defined follow-up period. The record identifies the endpoint and timeframe, but it does not state the operational event definition, including how relapse and death were handled in the calculation.

A one-year endpoint gives a fixed-time summary that can be communicated as a percentage. The accompanying 95% confidence interval, when reported, would describe the statistical uncertainty around the estimated percentage. It would not describe the range of outcomes for individual patients, nor would it account automatically for limitations such as incomplete follow-up or selection into treatment.

The endpoint is relevant to the study objective because the registry frames the study around survival without relapse after transplant. However, the primary estimate, confidence interval, and details of the endpoint analysis are not reported in the registry record. The endpoint's name alone therefore does not establish the observed rate, how precisely it was estimated, or whether every treated participant contributed equally to its calculation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as the percentage of participants with relapse-free survival at one year and lists a 95% confidence interval as its dispersion measure. It does not report the estimate, interval limits, or the statistical procedure used to calculate them. The method used for the primary analysis is not reported in the registry record.

What does a confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the method used to construct it. For a percentage, a narrower interval indicates greater statistical precision, while a wider interval indicates greater uncertainty. The interval is not a guarantee that the true value lies within its endpoints, and it does not describe the range of individual patient outcomes. Because no endpoints or estimate are posted, the precision of this study's primary result cannot be assessed.

What does a percentage at a fixed time require?

In general, a fixed-time percentage depends on how participants who have not reached the target follow-up time or who have incomplete outcome information are handled. A time-to-event approach can account for different follow-up durations, while a simple proportion requires a clearly defined denominator and outcome status. The registry names a one-year percentage but does not report whether it used a time-to-event estimator, a simple proportion, or another method. The treatment of censoring and missing endpoint information is also not reported.

What do the design labels imply?

Non-randomized allocation means treatment assignment was not recorded as random. A single-group design does not supply a concurrent randomized comparison group. In general, these features limit the ability to separate outcomes associated with treatment from differences in patient characteristics, prognosis, or other aspects of care. They also mean that a within-study outcome percentage should not be interpreted as a randomized comparison of strategies. The record does not report adjustment methods that might address measured differences between groups.

How should planning assumptions be read?

In general, a sample-size calculation estimates how many participants a future study might need under stated assumptions. It is a planning illustration, not an observed result and not a measure of the study's observed power. The record's planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; they also describe the effect to detect as a stated fraction of the observed effect. These assumptions do not change the registered study's single-group, non-randomized design, and the record does not report a detailed statistical plan or a sample-size justification for the trial itself.

Over-dispersion is a general concern when variation in data exceeds what a statistical model assumes. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. The registry does not identify an over-dispersion model or report whether this issue applies to the primary endpoint. Given the lack of a posted outcome estimate and analysis method, no trial-specific conclusion about over-dispersion is possible.

What information is needed to reproduce the analysis?

A reproducible endpoint analysis would require a clear outcome definition, the number of participants included, follow-up and censoring rules, handling of missing observations, and the estimator and confidence-interval method. The registry record does not report these details. It also does not report an interim analysis or a statistical plan specifying hypothesis tests, adjustment variables, or analysis populations. Those omissions prevent independent verification of the primary endpoint calculation from the registry information 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("Fludarabine Plus Busulfan")
n      <- c(50)
events <- c(28)
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  Fludarabine Plus Busulfan  50  28  56.0  41.3  70.0  42.3  68.8  42.2  68.9

11. Multiplicity, Missing Data and Analysis Populations

The record lists two outcome measures: the primary endpoint, percentage of participants with relapse-free survival at one year, and a secondary outcome, percentage of participants alive at one year. Neither outcome's estimate is reported in the registry record. The record also lists zero analyses, so it does not provide outcome analysis results or describe how the outcomes were statistically tested.

Multiplicity arises in general when several outcomes, time points, subgroups, or statistical tests are examined. Without an adjustment or a prespecified hierarchy, repeated testing can increase the chance of a false-positive finding. Whether any multiplicity adjustment was planned or applied is not reported in the registry record. The presence of a primary and secondary outcome alone does not establish which inferential procedures were used.

Missing-data handling is also not reported. The primary-outcome description states that four patients were inevaluable: three were less than one year post-transplant when the abstract was written, and one failed to engraft. The record does not specify how these patients were handled in the endpoint calculation, whether any other outcome information was missing, or whether incomplete follow-up was addressed with censoring or another method. The reasons given do not establish that missingness was unrelated to outcome.

The record distinguishes enrolled, treated, and inevaluable patients, but it does not define an intention-to-treat, per-protocol, or other analysis population. It also does not report how the one patient who died before transplant or the one who did not undergo transplant was handled for the primary endpoint. These details are important for understanding the denominator and scope of any outcome estimate, which is itself not posted.

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 (5.4%), anorexia (5.4%), nausea (5.4%), diarrhea (3.6%), vomiting (3.6%).

The registry records one Fludarabine Plus Busulfan safety group, with 56 participants at risk for serious adverse events and 21 affected. For other adverse events, 56 were at risk and 16 were affected. These are reported group counts; the record does not specify whether participants could be counted in both categories or provide further detail on the definitions and collection periods.

The listed serious adverse-event terms include Fever, Anorexia, and Nausea, each at 5.4%; Diarrhea and Vomiting, each at 3.6%; and Syncope (fainting) at 3.6%. These percentages are presented as term-specific registry figures. The record does not provide corresponding counts for each term, and the figures should not be added together because a participant may have experienced more than one event. The registry does not report deaths in this safety grouping.

These data describe reported safety events in the study group. With no like-for-like control comparison, they do not quantify how event frequency differs from another treatment. The safety record does not provide enough detail to assess event attribution, timing, severity grading beyond the serious/non-serious grouping, or completeness of collection.

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

The registry record establishes that a Phase 2 study evaluated stem cell transplantation in older patients with AML and identifies one-year relapse-free survival as its primary endpoint. It also records enrollment, treatment, and reasons why some patients were considered inevaluable. These registry entries help define the study's scope, but they do not supply the primary outcome result.

Without the one-year relapse-free survival estimate and its 95% confidence interval, the posted record does not show the observed rate or how precisely it was measured. The secondary one-year alive outcome is also named without a reported estimate. It is not possible to characterize either outcome's magnitude from the registry information.

The design limits what could be concluded even if an outcome estimate were available. This was a non-randomized, single-group study, not a randomized comparison against another approach. An outcome in this group would describe the experience of the treated participants, but could not on its own show what would have happened to comparable patients under a different strategy. The different regimen descriptions for CR and PR do not establish a comparative result because subgroup outcomes and randomized assignment are not reported.

The safety figures indicate that adverse events were recorded, including serious events and selected serious-event terms. They do not establish comparative safety, and the record does not give sufficient detail to assess attribution or event ascertainment fully. The distinction between reported event counts and a causal treatment effect is important in an uncontrolled study.

Thus, the registry record is informative about study design and reporting gaps, but it does not support a numerical conclusion about relapse-free survival or a comparative conclusion about treatment. The absence of a posted result should be distinguished from evidence that the outcome was favorable or unfavorable.

14. Why This Trial Matters Statistically

This study raises a statistically important question: how to summarize a one-year outcome in a treated population when follow-up may be incomplete for some participants. The registry notes that three patients were less than one year post-transplant when the abstract was written. For a fixed-time endpoint, the analysis must make its handling of incomplete follow-up clear. The record does not report that method, so the effect of follow-up availability on the estimate cannot be evaluated.

The study also illustrates the difference between estimating an outcome and estimating a treatment effect. A single-group design can describe the observed outcome among participants, but a randomized comparator is generally needed to support a direct causal comparison between strategies. Non-randomized allocation and the different conditioning regimens described for CR and PR make it especially important not to treat subgroup outcomes as though they arose from a controlled comparison.

Reporting the estimate together with its confidence interval is essential for judging precision. The registry names the interval but does not post its limits or the underlying estimate. Without those results, readers cannot assess statistical uncertainty, compare the result with a benchmark, or evaluate whether the data are compatible with a wide range of possible outcome rates.

The record's safety counts provide another reminder that event totals and event percentages need context: definitions, follow-up windows, denominators, and attribution all affect interpretation. In this case, important details are not reported. The study is therefore statistically instructive both for the endpoint and design it describes and for the reporting information needed to interpret clinical outcomes responsibly.

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 limitation of the registry record for statistical interpretation is that the primary result is absent. The one-year relapse-free survival estimate and its 95% confidence interval are not reported, and the secondary one-year alive estimate is also not reported. No numerical efficacy conclusion can be drawn from the posted information.

The record does not describe the endpoint calculation in enough detail to reproduce it. It does not define the relapse-free survival event components, explain the handling of censoring or missing follow-up, or identify the estimator used. Four patients are described as inevaluable for the primary endpoint, but the record does not explain the analysis population or the endpoint handling for these patients and the patients who did not undergo transplant.

Generalizability and comparative interpretation are constrained by the design. Allocation was non-randomized and the model was single-group; there is no like-for-like randomized control comparison. The registry gives different regimen descriptions for patients in CR and PR but does not report subgroup sizes or outcomes. It also does not explain the relationship between these regimen descriptions and the primary objective's wording about reduced-intensity treatment in CR or PR.

Safety interpretation is limited by the lack of reported event definitions, collection windows, attribution details, and death counts. The record provides selected adverse-event percentages but not counts for each term. It does not report an interim analysis, statistical analysis plan, multiplicity handling, or sample-size justification. These omissions mean that the results and their statistical conduct cannot be independently assessed from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Blood Stem Cell Transplantation for the Treatment of Older Patients With Acute Myelogenous Leukemia — NCT00623935.
• Registry record last updated 2016-04-08; status last verified 2016-03.
• Results first posted 2014-07-17.
• 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 identifies NCT00623935 as a completed Phase 2, non-randomized, single-group study sponsored by University of Michigan Rogel Cancer Center. It lists 56 enrolled patients and 54 treated patients. The primary objective was one-year relapse-free survival after transplant for older patients with AML in CR or PR, with a 7-8/8 HLA-matched unrelated donor.

The record describes FluBu2 as a reduced-intensity regimen for patients in CR and FluBu4 as a full-intensity regimen for patients in PR. Four patients were considered inevaluable for the primary endpoint for reasons stated in the record. Serious and other adverse-event counts, plus selected serious-event terms, are reported. The primary estimate, its confidence interval, the secondary outcome result, and detailed analysis methods are not reported in the registry record.