Non-Myeloablative Allogeneic Stem Cell Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Non-Myeloablative Allogeneic Stem Cell Transplantation (NCT00525876), a non-randomized na study. The primary outcome is Overall Survival at 100 Days Post Transplant (Number of Surviving Participants).

2. Clinical Question

The study's stated aims were to determine the safety and efficacy of the conditioning regimen and to identify factors associated with response and durable remission. The outcome recorded as primary is narrower than those broad aims: it is a count of participants alive at a specified post-transplant time. The registry record does not give a result for that count, nor does it describe results for response or durable remission.

Because treatment assignment was non-randomized, any comparison between donor groups may reflect differences in who received each transplant type, as well as differences in the transplant approach. The record does not describe how participants were assigned or whether the groups were comparable before transplantation. The clinical question can therefore be described from the stated outcome and groups, but the registry record does not support a causal comparison or a conclusion about the regimen's effect.

3. Trial Design

The registry describes a completed, non-randomized, parallel study sponsored by M.D. Anderson Cancer Center. The listed enrollment is 49. The study start is recorded as 2005-01 and primary completion as 2010-09. The phase is not reported in the registry record. Masking is listed as none. These design features describe how the registry classifies the study; they do not establish that treatment assignment or outcome assessment followed any particular procedure beyond what is stated.

The arm descriptions distinguish matched sibling transplantation from Allo MUD & MM transplantation. The latter is described as matched unrelated donor or mismatched sibling donor transplantation. The record says cyclophosphamide and fludarabine were used in conditioning, with rituximab included in the regimen. In the matched sibling description, cyclophosphamide 750 mg/m^2 is listed for Day -3, after fludarabine 30 mg/m^2 on Days -5 and -3. In the Allo MUD & MM description, cyclophosphamide 1000 mg/m^2 is listed for Day -3, after the same stated fludarabine schedule. The rituximab descriptions and remaining regimen details are incomplete in the registry record, so a full account of the regimens cannot be reconstructed.

Non-randomized allocation matters when interpreting group outcomes. The record does not explain the allocation process, whether clinical features influenced donor selection, or whether any adjustment was planned for differences between groups. As a result, arm-level outcome differences, if reported elsewhere, would not by themselves separate treatment-group effects from selection or other group differences. The registry record also does not report a statistical analysis plan. Its listed primary outcome is overall survival expressed as the number of participants alive 100 days after transplantation, with analysis described as per protocol.

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: Out of the 49 participants enrolled, 13 were excluded, not assigned to part of the two intervention study groups.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analysis was per protocol.

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 Overall Survival at 100 Days Post Transplant (Number of Surviving Participants), measured over 100 days post transplant.

The primary endpoint is the number of participants living at day 100 following non-myeloablative allogeneic stem cell transplantation. It is a count, not a reported survival percentage, time-to-event estimate, or comparison between groups. The endpoint description links the outcome to transplantation prepared with rituximab, cyclophosphamide and fludarabine, and identifies participants with advanced or recurrent mantle cell lymphoma.

A fixed-time survival outcome can provide a clinically interpretable snapshot of survival after a defined treatment event. It asks whether participants are alive at the specified time, rather than estimating how long each participant survives over a longer period. In general, a fixed-time count must be read in relation to the population assessed and the number with outcome data; those denominators and the observed count are not reported for the primary outcome in the registry record.

The record states that the primary analysis was per protocol. It does not explain the per-protocol criteria, how participants were handled if they did not receive the planned transplant or conditioning, or how missing survival status was treated. It also gives no primary endpoint estimate, confidence interval, or test result. Thus, the endpoint is clearly named and defined, but its observed value and precision cannot be evaluated from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives a limited description of statistical methods. It labels the primary outcome as a number of participants, specifies day 100 after transplant as the timeframe, and says the analysis was per protocol. It does not report the statistical test, an estimation method, a confidence interval, a model, covariate adjustment, or an analysis plan. Statistical concepts can help clarify what these omissions mean, but they cannot fill in methods that the record does not describe.

What does a count outcome represent?

A count outcome reports how many people met a defined condition. Here, the condition is being alive at day 100 after transplant. A count is easiest to interpret alongside the population assessed and the denominator eligible for the outcome assessment. Without those details, a count cannot by itself describe the proportion alive in a group. The registry does not report the primary outcome count or its denominator, so neither a group-level survival proportion nor a comparison can be read from this entry.

In general, a count can also be presented as a rate or converted to a proportion if the relevant denominator is defined. Those are different summaries, and they should not be substituted for one another without the required data. The outcome description specifies a number of surviving participants, not a rate, risk ratio, or time-to-event estimate.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimate under a specified statistical method. It indicates a range of values compatible with the data and method, rather than guaranteeing that the true value lies within that range. Its width is affected by factors such as the amount of information available and the variability of the outcome. The registry record reports no confidence interval for the primary outcome, so its precision cannot be assessed.

A test result and an estimate answer different questions. A test may assess compatibility with a particular null hypothesis, while an estimate describes the size and direction of an outcome or contrast. A p-value alone, if available, would not give the magnitude or precision of an effect. In this record, neither a p-value nor an effect estimate is reported for the primary outcome.

Why does non-randomized allocation matter?

In general, random allocation helps balance both measured and unmeasured characteristics between groups on average. Non-randomized allocation does not ensure that balance. Differences between groups may arise because of participant characteristics, donor availability, clinical choices, or other factors. These are general considerations, not claims about what happened in this study: the registry does not describe the allocation process or the characteristics used in choosing a transplant group.

Statistical adjustment can sometimes address measured differences, but it cannot automatically resolve unmeasured confounding. The registry record does not report adjusted analyses, covariates, matching, weighting, or another approach to account for group differences. The record's warning that the groups are not a like-for-like control comparison is therefore central to interpreting any possible group contrast.

What does per-protocol analysis mean in general?

In general, a per-protocol analysis evaluates participants who meet criteria for receiving or completing the planned study treatment. The specific criteria vary by study and must be stated to know who is included. The registry labels its primary analysis per protocol but does not define the criteria, list the analysis population, or explain how departures from the protocol were handled. It also does not explain whether all participants with missing day-100 status were excluded, included under an assumption, or handled by another method.

Different analysis populations can answer different questions. An analysis of participants according to treatment assignment, when such assignment exists, differs conceptually from an analysis limited to protocol adherence. With non-randomized allocation, the usual randomized assignment framework does not apply in the same way. No further analysis population is described in the registry record.

How should the planning assumptions be read?

The record describes planning illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation and a normal approximation. The illustration is framed around detecting a stated fraction of the observed effect. These are planning assumptions, not a reported statistical analysis plan for the completed trial. The record does not report a planned target effect, a sample-size justification used by the investigators, or an interim-analysis plan.

Sample-size illustrations indicate what might be needed under their assumptions; they do not describe the precision actually achieved in a completed study. They are never observed power. The primary effect needed to anchor the stated illustration is not reported in the registry record, so the planning assumptions cannot be used to infer the study's observed result or its evidential strength.

For count outcomes involving events, general statistical methods may need to account for variation beyond a simple model's assumptions. Over-dispersion means that observed variability is greater than a model expects; ignoring it can make uncertainty estimates too small. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report such a model or a dispersion assessment, and the primary endpoint is described as a survivor count rather than an event-count rate.

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("Matched Sibling Transplant", "Allo MUD & MM")
n      <- c(16, 20)
events <- c(16, 19)
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  Matched Sibling Transplant  16  16  100.0  79.4  100.0  80.6  100.0  80.5  99.9
ARM  Allo MUD & MM  20  19  95.0  75.1  99.9  76.4  99.1  76.2  98.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the number of participants alive at 100 days post transplant, and reports no analyses. It does not state whether additional outcomes were prespecified in a protocol or analysis plan, nor does it describe a testing hierarchy or any adjustment for multiple comparisons. The broad study aims include safety, efficacy, response and durable remission, but the registry entry does not provide corresponding analysis results. It is therefore not possible to determine from this record how multiplicity across outcomes or subgroup analyses was addressed.

In general, testing many outcomes or comparisons can increase the chance of finding an apparently notable result by chance. Methods such as prespecifying a primary outcome or adjusting for multiple testing can address aspects of this concern, but the registry record does not say which, if any, were used beyond identifying the primary outcome. No interim analyses or stopping rules are reported.

Missing-data handling is also not reported. The primary outcome is defined at a fixed time after transplant, but the entry does not state how participants without known day-100 status were treated. It does not describe follow-up completeness, censoring, imputation, sensitivity analyses, or reasons for missing outcome information. Such details matter because an analysis can be affected if missing status is related to prognosis or treatment experience.

The primary outcome population is described as per protocol. The record does not give the criteria for that population or report a separate analysis in another population. It also does not state how participants who did not follow the intended regimen were handled. As a result, the population represented by the stated primary analysis cannot be fully assessed from the registry record.

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: allergic reaction (6.2%), encephalitis (6.2%), aspergillus infection (6.2%), prolonged hospitalization due to graft vs host disease (6.2%), cmv pneumonia (6.2%).

The safety entry reports serious and other adverse events separately for the transplant groups. For Matched Sibling Transplant, the serious adverse event count is 3 among 16 participants at risk, and the other adverse event count is 15 among 16 at risk. For Allo MUD & MM, the serious adverse event count is 2 among 20 participants at risk, and the other adverse event count is 20 among 20 at risk. These are descriptive registry counts; they are not adjusted comparisons.

The listed serious adverse event terms include Allergic Reaction, Encephalitis, Aspergillus Infection, Prolonged Hospitalization due to Graft vs Host Disease and CMV Pneumonia, each reported as 6.2%, and Shortness of Breath, reported as 5.0%. The record does not clarify whether participants could contribute to more than one term or how each percentage was calculated. The terms should not be assumed to be mutually exclusive, nor should the percentages be interpreted as risks over a specified follow-up period without further information.

Deaths are not reported in the safety entry. The registry does not state the method of adverse event collection, severity grading, exposure time, or attribution to treatment. Because the study was non-randomized, the group figures do not establish that differences in event counts were caused by the transplant approach.

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

The record establishes that a completed, non-randomized study was registered for people with advanced or recurrent mantle cell lymphoma undergoing allogeneic stem cell transplantation with a rituximab-containing nonablative conditioning regimen. It identifies overall survival at 100 days after transplant as the primary outcome and describes the analysis population as per protocol. It also records safety counts for the named transplant groups.

It does not report the primary survival count, an estimate of survival, uncertainty around an estimate, or a statistical test. Therefore, the posted results do not show the observed day-100 survival outcome. No conclusion about the size, direction, or precision of a primary effect can be drawn from the registry entry. The lack of a reported result should not be read as evidence of no effect, no difference, or an unfavorable result.

The safety counts and serious adverse event terms provide descriptive information, but they do not establish comparative safety. The groups were not randomized, and the registry cautions that they are not like-for-like controls. The entry also lacks details about baseline characteristics, allocation, follow-up and event ascertainment that would be needed to assess how comparable the group summaries are.

General statistical interpretation depends on clearly identifying the outcome, analysis population, denominator, estimate and uncertainty. Here, the outcome definition and a per-protocol label are present, but the primary numerical result and key analysis details are absent. The registry record can therefore describe the study question and some reported safety data, but it cannot support a quantitative conclusion about the primary endpoint or a causal treatment comparison.

14. Why This Trial Matters Statistically

This study is statistically instructive because it makes clear that a named primary endpoint is not the same as a reported result. The record defines survival as the number of participants alive at day 100 after transplant, yet does not give the observed count or an estimate. Without those values, readers cannot assess the outcome's magnitude or precision. A clearly stated endpoint helps frame the question, but analysis results are necessary to answer it.

The non-randomized design also underscores the distinction between describing outcomes and attributing them to treatment. Comparisons between transplant groups can be influenced by how participants entered each group and by differences in their characteristics. The registry explicitly warns that the arms are not a like-for-like control comparison. That qualification should guide interpretation even when descriptive safety figures are available.

The entry illustrates why denominators and analysis populations matter. The primary analysis is labeled per protocol, while the safety summaries report their own at-risk counts. These descriptions do not establish that the same populations were assessed, and the registry does not explain the per-protocol criteria or missing-data handling. Clear reporting of analysis populations would help readers understand whom each result represents.

Finally, planning assumptions and completed-study results have different roles. Planning illustrations can show how sample-size requirements depend on assumptions, but they cannot stand in for an observed effect or its uncertainty. The registry's stated assumptions should not be mistaken for a trial analysis plan, and planning calculations are not observed power. The record demonstrates the importance of separating design information, outcome definitions, descriptive safety reporting and inferential results.

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.

Several important details are absent from the registry record. It does not report the primary day-100 survival count, its denominator, an effect estimate, a confidence interval or a test result. Although the analysis is described as per protocol, the criteria defining that population are not given. The record also does not explain missing outcome handling, follow-up completeness, or whether participants who did not receive the planned transplant were included in any analysis.

The non-randomized allocation limits interpretation of comparisons between the transplant groups. The registry does not describe how allocation occurred, provide baseline characteristics for assessing comparability, or report adjustment for potential confounding. The arm regimen descriptions are incomplete, so the full treatment approaches cannot be evaluated from the entry. The phase is not reported in the registry record.

Safety reporting is also limited. The registry provides at-risk and affected counts and a list of serious adverse event terms with percentages, but does not describe event ascertainment, grading, exposure time, attribution, overlap between terms, or the basis for the listed percentages. Death counts are not reported in the safety entry.

The registry lists one outcome measure and no analyses, and it does not report a statistical analysis plan, multiplicity strategy, interim analyses or sample-size justification. These omissions constrain assessment of both the primary result and the robustness of any planned comparisons. They are limitations of what can be interpreted from the registry record and do not establish that the information was absent from other study documents.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Non-Myeloablative Allogeneic Stem Cell Transplantation — NCT00525876.
• Registry record last updated 2011-12-07; status last verified 2011-11.
• Results first posted 2011-12-07.
• 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

NCT00525876 is a completed, non-randomized, parallel study sponsored by M.D. Anderson Cancer Center. The record lists enrollment of 49, a start date of 2005-01 and primary completion in 2010-09. It concerns non-myeloablative allogeneic stem cell transplantation for advanced or recurrent mantle cell lymphoma, using a rituximab-containing conditioning regimen. The registry identifies matched sibling and Allo MUD & MM transplant groups and states that the primary analysis was per protocol.

The primary outcome is the number of participants alive at 100 days after transplant. Its observed result and statistical analysis are not reported in the registry record. Safety counts and serious adverse event terms are listed, but the record does not provide enough detail to treat the groups as a randomized comparison or fully assess event ascertainment. The phase is not reported in the registry record.