Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies (NCT01427881), a na phase 2 study. The primary outcome is Chronic GVHD Requiring Systemic Immunosuppressive Treatment.

2. Clinical Question

3. Trial Design

This was a phase II, completed, single-group study sponsored by Fred Hutchinson Cancer Center. The registry lists 43 participants as enrolled. The recorded start was 2011-09 and the primary completion was 2014-06. These dates describe the record’s study timeline; they do not supply the follow-up status or analysis date for each participant.

The study addressed prevention of chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation in patients with hematological malignancies. Its intervention of interest was cyclophosphamide administered after transplant as prophylaxis. The treatment arm is described as including total-body irradiation, peripheral blood stem cell transplantation, and cyclophosphamide prophylaxis. Other listed interventions include cyclosporine, fludarabine phosphate, busulfan, and allogeneic hematopoietic stem cell transplantation. The detailed arm description is incomplete in the registry record, so the complete regimen and its variation between patients cannot be established from that description.

With one group and no masking, the design is suited to describing outcomes among treated participants, but it does not isolate the effect of cyclophosphamide from other aspects of transplantation, supportive care, or patient characteristics. There is no like-for-like control arm in the record. Therefore, a difference from the design target or from an external benchmark would not by itself establish a treatment effect.

The primary endpoint was planned for assessment at 1 year after transplantation. The registry describes a target reduction in cumulative incidence from approximately 35% to approximately 15%, and states that a sample size of 42 patients provides 90% power under a one-sided 5% type-1 error for that goal. This is a planning statement, not an observed result or a measure of the achieved power. The primary endpoint result itself is not reported in the registry record.

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

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 Chronic GVHD Requiring Systemic Immunosuppressive Treatment, measured over At 1 year after transplantation.

The primary endpoint was chronic graft-versus-host disease requiring systemic immunosuppressive treatment, expressed as a percentage of patients and assessed at 1 year after transplantation. The registry specifies that chronic disease would be defined by National Institutes of Health criteria. Requiring systemic treatment makes the endpoint more focused than counting every possible symptom or finding: it captures chronic graft-versus-host disease considered to warrant treatment. It remains an endpoint defined by both clinical criteria and a treatment decision.

The endpoint is framed as cumulative incidence. In general, cumulative incidence describes the probability of an event occurring over a stated period while recognizing that other events may prevent the event of interest from occurring or being observed. The registry record does not report which competing events were incorporated, the precise estimator, or the handling of censoring. Those details matter for interpreting a cumulative-incidence estimate.

The registry identifies a 95% confidence interval as the measure of dispersion for the endpoint. In general, a confidence interval communicates the statistical uncertainty around an estimated event proportion; a narrower interval indicates greater precision under the method used. Neither the primary point estimate nor its confidence interval is reported in the registry record. Thus the endpoint definition and intended assessment time are available, but the frequency and precision of the observed primary outcome cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s main statistical feature is its single-group design. In a single-group study, outcomes are observed among participants receiving the study approach, rather than contrasted with an assigned concurrent control group. This can describe the frequency of outcomes in the enrolled group, but it cannot remove differences in patient characteristics, clinical care, or time that might explain an apparent contrast with an external benchmark. General statistical interpretation therefore distinguishes an observed event proportion from a causal treatment effect.

What does the endpoint estimate represent?

The primary endpoint is a percentage of patients with chronic graft-versus-host disease requiring systemic immunosuppressive treatment at 1 year after transplantation. In general, a percentage summarizes how common an event was in a defined group and period. For this endpoint, the numerator would concern qualifying chronic disease and the denominator would depend on the analysis population and follow-up rules. The registry record does not provide the endpoint count, denominator used in the primary analysis, or estimate. The 43 enrolled participants should not automatically be assumed to be the analysis denominator.

The endpoint is described as cumulative incidence. In general, cumulative incidence estimates the probability of an event by a given time in the presence of events that can preclude the event of interest. The exact estimator, definition of competing events, and censoring approach are not reported in the registry record. Consequently, the method used to produce any cumulative-incidence estimate cannot be evaluated from the available information.

How should the confidence interval be read?

The registry names a 95% confidence interval for the primary endpoint. Generally, a confidence interval shows the range of values reasonably compatible with the data under the specified statistical procedure. It describes uncertainty in an estimate; it is not a range containing a fixed proportion of individual outcomes, and it does not by itself show whether an effect is clinically important. Precision depends on factors such as the amount of information observed and the method used. Here, neither the estimate nor its interval is reported in the registry record, so neither the outcome level nor its precision can be assessed.

What does the planning statement say?

The endpoint description says that a sample size of 42 patients provides 90% power to observe a reduction in cumulative incidence from approximately 35% to approximately 15% at 1 year, with one-sided 5% type-1 error. This is a design statement based on the stated target. In general, power is the probability of detecting a specified effect under assumptions when that effect is present. It is not a description of what happened in the enrolled group, and it does not indicate the probability that a treatment is effective. The enrollment listed in the record is 43, but the primary outcome and analysis population are not stated. The design statement cannot substitute for an outcome estimate.

A separate planning illustration may use assumed effects and statistical conventions to show sample-size requirements. Such figures are planning aids, not observed study findings. They do not change the single-group nature of this trial and cannot create a treatment comparison absent from the design. If a recalculated value differs from the sponsor’s own analysis, the sponsor’s analysis takes precedence; no primary endpoint analysis is reported in the record to compare against.

Why does over-dispersion matter generally?

For count or rate outcomes, over-dispersion means the observed variability exceeds what a simple statistical model assumes. Ignoring it can make uncertainty estimates too small and confidence intervals too narrow. This is a general consideration for count-based analyses, not a reported feature of this study’s primary endpoint. The registry record does not specify a model for the primary endpoint, so it does not establish whether over-dispersion was relevant or how it was addressed.

Statistical analysis also depends on clear definitions of the analysis population, outcome timing, and handling of incomplete observations. Those elements determine who contributes to an estimate and how partial follow-up is used. They are not reported in the registry record. Without them, the primary result cannot be reconstructed or independently checked from the information available.

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 (TBI, PBSCT, and Cyclophosphamide GVHD P")
n      <- c(43)
events <- c(7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment (TBI, PBSCT, and Cyclophosphamide GVHD P  43  7  16.3  6.8  30.7  8.1  30.0  8.2  30.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including donor engraftment; acute graft-versus-host disease at different grades; duration of systemic immunosuppressive treatment; persistent or recurrent malignancy; non-relapse mortality; overall survival; disease-free survival; and hematologic recovery. Considering multiple outcomes creates a multiplicity issue: the more statistical questions assessed, the greater the chance that at least one result may appear noteworthy by chance. In general, a prespecified hierarchy or multiplicity adjustment can help control interpretation, but the statistical plan and any such approach are not reported in the registry record.

The record lists 10 outcome measures and no analysis entries. That does not establish that no analyses were conducted; it means analysis details and estimates are not available in the registry record. The primary outcome estimate, confidence interval, and secondary outcome results are not reported in the information available.

Missing-data handling is also not reported in the registry record. This matters because outcome assessment at 1 year may depend on follow-up completeness, censoring rules, and how participants without an observed assessment are treated. The analysis population and the number contributing to the primary endpoint are not reported. No assumption about missing outcomes, exclusions, or imputation can therefore be made.

In general, a complete interpretation would require the prespecified analysis population, outcome definitions, methods for censoring and competing events, and any sensitivity analyses for incomplete follow-up. Whether these procedures were specified or applied is not reported in the registry record.

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: graft failure/poor graft function (100.0%), infection/fever (30.2%), gvhd (14.0%), disease recurrence/mrd (9.3%), headache (4.7%).

The registry reports a treatment group with 43 participants at risk for serious adverse events and 22 affected, and 43 at risk for other adverse events and 40 affected. These are separate registry counts. Participants may have experienced events in both categories, so the counts should not be added to describe a number of unique people. The record also reports 11 deaths; it does not state in the available information whether these deaths were attributed to treatment or to a particular cause.

The listed serious-event terms include graft failure/poor graft function at 100.0%, infection/fever at 30.2%, GVHD at 14.0%, disease recurrence/MRD at 9.3%, headache at 4.7%, and bradycardia at 2.3%. The denominator and counting rules for these term-level percentages are not reported in the registry record. In particular, the 100.0% entry should not be taken to mean that all enrolled participants experienced that event.

Adverse-event counts describe reported events within this group. With no control group, they do not estimate an excess risk compared with another treatment strategy. Event attribution, timing, and detailed grading are not reported in the registry record, limiting interpretation of how these events relate to the study intervention.

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

The study addresses a clinically important statistical problem: quantifying chronic graft-versus-host disease requiring systemic treatment after allogeneic peripheral blood stem cell transplantation. The registry defines the endpoint using National Institutes of Health criteria and sets the assessment at 1 year after transplantation. It also states a planning target of reducing cumulative incidence from approximately 35% to approximately 15%.

What the posted information does not establish is the observed primary outcome. The estimate and its 95% confidence interval are not reported in the registry record. It is therefore not possible to say how often the endpoint occurred in the study group, how precise an estimate was, or how the observed outcome compared with the stated design target.

The single-group design also limits what any event rate could mean. A rate among treated participants would describe their experience under the study approach, but would not by itself show what would have happened to comparable participants under a different prophylaxis strategy. Without a concurrent comparator, differences from an external reference can reflect differences in participants, treatment context, follow-up, or outcome ascertainment as well as treatment.

The design statement about power is a planning assumption, not evidence that the trial achieved a particular statistical result. Likewise, the adverse-event counts provide safety information about the group but do not establish comparative safety or causation. The registry record does not report the analysis population, missing-data approach, or detailed statistical methods needed to assess these issues further.

Accordingly, the record supports a clear account of the study’s purpose and design, but not a quantified conclusion about the primary endpoint. It cannot show from the posted results whether the planned goal was met or whether cyclophosphamide changed the risk of chronic graft-versus-host disease.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a design objective and an observed result. The registry states a specific primary endpoint, assessment time, and target reduction, as well as a planned sample size and power assumption. Yet the primary estimate and confidence interval are not reported in the registry record. Without those results, the central statistical question remains unanswered in the posted information.

It also demonstrates why a single-group design must be interpreted differently from a randomized comparison. A treated-group event frequency can be useful for describing outcomes in a defined transplant setting, but it does not estimate a contrast against an alternative strategy. Even a rate that appears to match a design target would not alone attribute that outcome to cyclophosphamide.

The study’s context adds further statistical considerations. The listed conditions cover a broad range of hematological malignancies, while outcomes such as chronic graft-versus-host disease depend on follow-up and clinical assessment. How the analysis handled variation in participants, competing events, and incomplete follow-up is not reported. These omissions affect the ability to judge precision and generalizability.

Finally, the safety counts show why denominators and event definitions matter. Group-level counts and term-level percentages are not interchangeable, and the term-level denominators are not reported. A careful statistical reading separates what the registry documents—design, endpoint definition, selected safety counts—from what it does not document: the primary efficacy estimate, uncertainty, and comparative effect.

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 most important limitation in interpreting the registry record is that the primary endpoint result is not reported. Although the endpoint definition, timeframe, and intended confidence interval are specified, no observed percentage or interval is available. The listed count of 43 enrolled participants does not reveal how many contributed to the primary endpoint analysis.

The single-group design has no concurrent control. As a result, the record cannot support a controlled estimate of the effect of cyclophosphamide relative to another prophylaxis strategy. The treatment context also includes transplantation and other listed interventions, and the available arm description does not establish which regimen elements every participant received.

The registry lists a broad range of hematological malignancies, but participant characteristics and disease-specific outcome information are not reported in the available record. The degree to which findings might apply across these conditions cannot be assessed. Follow-up completeness, missing-data rules, censoring, and competing-event methods are also not reported, despite the primary outcome being defined at 1 year.

The registry gives a design power statement but does not report the analysis methods, outcome estimates, or analysis population. No analysis entries are listed. The safety record includes adverse-event counts and term-level percentages, but does not report term denominators, detailed attribution, or timing in the available information. These limitations prevent assessment of the primary outcome’s magnitude, precision, and comparative interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies — NCT01427881.
• Registry record last updated 2017-05-19; status last verified 2017-05.
• Results first posted 2017-05-19.
• 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

This completed phase II study, sponsored by Fred Hutchinson Cancer Center, evaluated post-transplant cyclophosphamide for prevention of chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation in patients with hematological malignancies. It was a single-group study with 43 participants enrolled; the recorded start was 2011-09 and primary completion was 2014-06.

The primary endpoint was chronic graft-versus-host disease requiring systemic immunosuppressive treatment at 1 year, defined by National Institutes of Health criteria. The registry record does not report the primary estimate or its 95% confidence interval, and lists no analysis entries. It reports adverse-event counts for the treatment group, but lacks details needed for comparative safety interpretation. The design can describe outcomes in the treated group, but cannot establish a causal treatment contrast.