A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies (NCT01036009), a non-randomized phase 2 study. The primary outcome is Relapse at 2 Years Post-transplant..

2. Clinical Question

The study’s stated aim is to assess whether immune modulation can achieve full donor chimerism and whether that outcome may be associated with reduced relapse risk. Its brief summary describes this as a hypothesis, not as an established finding. The registered primary outcome is relapse at 2 years post-transplant; full donor chimerism is part of the study’s objective and intervention approach, but is not the listed primary outcome.

The question is clinically consequential because relapse after transplant is the outcome the study seeks to address. Statistically, however, the record does not provide the observed relapse count, an estimate comparing groups, or an uncertainty interval. It therefore does not allow a reader to quantify relapse occurrence or the precision of a treatment contrast from the registry results.

3. Trial Design

This is a phase II study with non-randomized allocation, no masking, and a parallel model. The registry lists enrollment as 43 and status as completed. The study start is recorded as 2009-10 and primary completion as 2014-07. The sponsor is University of California, San Francisco.

The two groups differ by their recorded clinical circumstances and management. Group I is observation for patients with full donor chimerism and no evidence of MRD. These patients continue clinical monitoring for acute and chronic graft-versus-host disease and relapse until 3 years post-transplant, with repeat chimerism testing at 12 and 24 months post-transplant. Group II receives withdrawal of immunosuppression and donor lymphocyte infusions between days 60-365 post-transplant, or until full donor chimerism is achieved. The group also has clinical monitoring and repeat chimerism testing as in Group I.

Because allocation is non-randomized, these groups should not be treated as interchangeable arms of a randomized trial. In particular, the Group I description specifies full donor chimerism and no evidence of MRD, while Group II is defined by the intervention approach. Differences in outcomes, if available, could reflect differences in these circumstances as well as the intervention. The registry explicitly cautions that this is not a like-for-like control comparison.

The primary outcome is relapse at 2 years post-transplant. Listed secondary outcomes are survival at 2 years post-transplant and the incidence of acute and chronic GVHD. The registry also records six outcome measures, but a complete description of every measure is not available in the information recorded for this analysis. The number of outcome analyses is listed as zero; no analysis results are available 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.

Before assignment: 5 eligible patients relapsed/died before assignment to a study arm

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 Relapse at 2 Years Post-transplant., measured over 2 years post transplant..

The primary endpoint is the number of participants with relapse at 2 years post-transplant. The registry defines relapse as >5 % blasts in bone marrow. This is a binary event outcome: each participant is classified according to whether the defined event occurred during the stated timeframe. The record does not report the number of relapses or the number assessed for this endpoint.

In general, relapse is a direct clinical outcome for a study whose stated objective is to reduce relapse risk after transplant. A fixed follow-up time makes the time point of interest explicit, but interpretation still depends on knowing how many participants were evaluated, how many experienced relapse, and how missing follow-up was handled. Those details are not reported in the registry record.

The registry’s brief summary discusses full donor chimerism as an objective and a possible link to leukemia-free survival. That hypothesis should be distinguished from the registered primary outcome: the listed endpoint measures relapse, not achievement of full donor chimerism or leukemia-free survival. Results for the primary endpoint are not reported in the registry record, so neither the observed event frequency nor an estimate of its uncertainty can be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a phase II, non-randomized, parallel study with no masking. It does not report a detailed statistical analysis plan. The number of outcome analyses is listed as zero, and the registry does not report an analysis population, a primary-outcome estimate, or inferential results. The methods concepts below are general explanations for interpreting clinical trial statistics; they should not be taken as a description of analyses performed in this study unless the registry specifically records them.

What does a binary outcome measure?

The primary outcome is recorded as the number of participants with relapse, with relapse defined as >5 % blasts in bone marrow at 2 years post-transplant. General explanation: a binary outcome records whether an event occurred or did not occur for each participant. A count of events is easiest to interpret alongside the number of participants evaluated. Without that denominator, the count alone does not describe an event frequency. Neither the relapse count nor its denominator is reported in the registry record.

What would a group comparison require?

General explanation: an unadjusted comparison of binary outcomes typically uses event counts and denominators for each group to estimate how outcomes differ. An effect estimate describes the direction and magnitude of a contrast; a confidence interval describes the uncertainty around that estimate under the method’s assumptions. A p-value, when used, addresses compatibility between the observed data and a specified null hypothesis. These quantities answer different questions and should not be treated as substitutes for one another.

For this study, no primary-outcome counts, group contrast, confidence interval, or p-value are reported in the registry record. More fundamentally, the groups are non-randomized and are not described as like-for-like. General explanation: a numerical contrast between non-randomized groups may be confounded when factors related to group membership also relate to the outcome. Statistical adjustment can address measured factors under suitable assumptions, but it cannot guarantee removal of unmeasured confounding. The registry does not report an adjustment strategy.

How should time and follow-up be considered?

The primary endpoint is specified at 2 years post-transplant. Group I is described as monitored for relapse and acute and chronic GVHD until 3 years post-transplant, with repeat chimerism testing at 12 and 24 months. Group II has monitoring and repeat testing as in Group I. General explanation: an outcome assessed at a fixed time requires clarity about whether participants were observed through that time and how incomplete follow-up was treated. Time-to-event methods can use information about when events occur and account for differing observation times under defined assumptions. The registry does not report whether a time-to-event analysis was used for relapse, how censoring was handled, or how participants without complete follow-up were treated.

What is the role of the planning illustration?

The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. It specifies that non-time-to-event illustrations are expressed as participants per arm. These are planning assumptions, not results from the trial and not evidence of observed power. The registry does not report a design justification or the sample-size assumptions used when the trial was planned. The illustration should therefore be understood as a separate planning exercise, not as the original protocol’s documented rationale.

General explanation: sample-size planning asks how much information a future study might need to detect an effect under chosen assumptions. It depends on the assumed effect, variability or event rate, allocation, significance level, and desired power. If an assumed effect comes from an observed estimate, uncertainty in that estimate matters: an unstable estimate may not be a reliable planning target. A planning calculation cannot show that a completed study had a particular probability of detecting its true effect after the fact. No observed-power conclusion is warranted from the information in the registry record.

How should event counts and dispersion be understood?

The primary outcome is a participant count, not a continuous measurement. General explanation: count outcomes often have variability that increases with their mean. If the variability exceeds what a simple count model assumes, this is called over-dispersion; ignoring it can make uncertainty estimates too small. Whether over-dispersion is relevant depends on the particular outcome and model. The registry does not report a count model or a dispersion assessment for the primary outcome, and no such modeling should be inferred from the endpoint’s count format alone.

In summary, the registered design and endpoint can be described, but the analysis methods and primary-outcome results needed for an inferential interpretation are not reported in the registry record. General statistical concepts clarify what those missing elements would ordinarily contribute; they do not fill in the absent trial-specific results.

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 I: Observation", "Group II: Intervention")
n      <- c(17, 26)
events <- c(6, 4)
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 I: Observation  17  6  35.3  14.2  61.7  17.3  58.7  17.3  59.0
ARM  Group II: Intervention  26  4  15.4  4.4  34.9  6.2  33.5  6.3  33.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and names survival at 2 years post-transplant, acute GVHD incidence, and chronic GVHD incidence as secondary outcomes. Relapse at 2 years post-transplant is listed as the primary outcome. The record does not report a multiplicity strategy, such as whether secondary outcomes were intended to be confirmatory or how error rates across multiple tests would be handled.

General explanation: assessing several outcomes or conducting several statistical tests increases the chance that at least one result may appear notable by chance if each test is interpreted independently. A prespecified testing hierarchy or adjustment can help address this issue, but no such plan is reported in the registry record. Since outcome analyses are listed as zero and results are not reported, there are no posted inferential results to evaluate for multiplicity.

The registry does not report missing-data counts, reasons for missingness, imputation methods, or sensitivity analyses. It also does not specify the analysis population for the primary endpoint, such as which participants were included in its denominator. These details matter because incomplete follow-up can affect an event count and the interpretation of a fixed-time outcome. General explanation: methods for missing data rely on assumptions about why values are missing; different assumptions can lead to different conclusions.

The record therefore does not support a judgment about the handling of missing outcomes, the composition of the analysis population, or adjustment for multiple comparisons. These are reporting gaps, not evidence that any particular method was or was not used in practice.

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: intervention-related-death (3.8%).

The registry records serious and other adverse-event fields for both groups. For Group I, the at-risk counts and affected counts are each recorded as 0. Because the at-risk count is 0, those entries do not establish a zero event rate or permit a meaningful safety comparison with Group II. The registry records 26 at risk for each adverse-event category in Group II, with 1 affected for serious events and 9 affected for other events.

The record lists “intervention-related-death” among the top serious terms at 3.8%. That entry is a registry-listed term and percentage; the denominator and further details needed to interpret it are not reported in the registry record. The death-count fields are not populated with a reported value. The listed term and percentage should not be used to infer a death count or a comparative risk.

General explanation: adverse-event counts describe recorded events or affected participants within the registry’s reporting categories. They do not by themselves establish that an intervention caused an event. The record does not explain whether the serious and other categories are mutually exclusive, how events were attributed, or how the reported percentage was calculated. These figures should therefore be read as limited registry safety entries, not as a complete comparative safety analysis.

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

The record establishes that a phase II study examined withdrawal of immunosuppression and donor lymphocyte infusions after allogeneic transplant for pediatric hematologic malignancies. It specifies a primary endpoint of relapse at 2 years post-transplant and gives the relapse definition as >5 % blasts in bone marrow. It also describes two non-randomized groups and lists survival and GVHD outcomes.

Those details do not establish whether relapse was more or less frequent, whether survival differed, or whether the intervention changed any outcome. The registry does not report the primary-outcome result or results for the listed secondary outcomes. No comparative effect estimate or uncertainty interval is available. The study’s stated hypothesis about full donor chimerism and leukemia-free survival must not be mistaken for a finding.

The non-randomized group structure is important. Group I is described as having full donor chimerism and no evidence of MRD, while Group II receives the intervention. The registry explicitly notes that the arms are not a like-for-like control comparison. General explanation: observed differences in non-randomized groups can arise from differences in group membership, clinical status, or other factors as well as from an intervention. The design description alone cannot separate those possibilities.

The recorded adverse-event entries offer only limited information: Group II has reported at-risk counts and affected counts, while Group I has zero at-risk counts in these fields. The listed serious term and percentage do not provide a complete safety comparison or establish causation. The outcome and safety information should therefore be interpreted within the bounds of what the registry actually records.

In practical statistical terms, the record describes the question and study structure more fully than it documents the results. It does not support a conclusion about the size, direction, or precision of an effect. An absent result is neither evidence of benefit nor evidence of no effect.

14. Why This Trial Matters Statistically

This trial raises a useful statistical issue: a biologically motivated intervention can be difficult to evaluate when the comparison groups are formed without randomization. The study’s stated aim concerns immune modulation and donor chimerism after transplant, while the registered primary endpoint is relapse at 2 years post-transplant. Keeping the proposed mechanism, intermediate objective, and clinical endpoint distinct is essential when interpreting a trial.

The group definitions make the comparison especially important to handle cautiously. Observation is described for patients with full donor chimerism and no evidence of MRD; the intervention group is described by immunosuppression withdrawal and donor lymphocyte infusions. The registry notes that the arms are not a like-for-like comparison. General explanation: treatment contrasts are most directly interpretable when groups differ mainly in the assigned intervention. When assignment is non-randomized, measured and unmeasured differences can complicate causal interpretation.

The record also illustrates why outcome definitions and reporting completeness matter. It defines relapse using a bone marrow blast threshold and fixes the primary endpoint at 2 years post-transplant, but does not report the event count, denominator, or estimate. Without those, readers cannot assess the outcome frequency or its precision. The same distinction applies to the listed secondary outcomes: naming an outcome does not report its result.

Finally, the adverse-event entries show why denominators and category definitions are indispensable. A zero at-risk count cannot be read as a zero-risk finding, and a listed term and percentage without a reported denominator cannot establish comparative safety. These are general lessons in interpreting clinical registry records, grounded in the specific limits of this study’s reporting.

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 primary limitation for interpretation is that the registry record does not report the primary relapse result. It also does not report group-specific relapse counts, denominators, a comparative estimate, or its uncertainty. The listed secondary outcomes have no reported results in the registry record.

The non-randomized allocation and the different descriptions of the groups limit causal interpretation. Group I is defined by full donor chimerism and no evidence of MRD, while Group II receives withdrawal of immunosuppression and donor lymphocyte infusions. The registry expressly cautions that the arms are not a like-for-like control comparison. No adjustment approach is reported.

The analysis population, missing-data handling, follow-up completeness for the primary endpoint, and approach to multiple outcomes are not reported in the registry record. Although the record specifies a primary outcome time point and provides monitoring details for the groups, it does not say how incomplete observation was handled in the analysis.

Safety information is also limited. Group I has no participants recorded as at risk in the adverse-event fields, and the registry does not explain the denominator for the listed 3.8% serious-event term. Death-count fields do not contain a reported value. The record does not give enough context to make a full safety comparison.

These limitations describe what the registry entry does not document; they do not show that analyses or procedures were absent from the completed study. The registry record does not report a detailed statistical analysis plan, design justification, or interim-analysis information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies — NCT01036009.
• Registry record last updated 2016-06-23; status last verified 2016-05.
• Results first posted 2014-10-31.
• 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

NCT01036009 is a completed phase II, non-randomized, parallel study sponsored by University of California, San Francisco. It records enrollment of 43, a study start of 2009-10, and primary completion in 2014-07. The study concerns withdrawal of immunosuppression and donor lymphocyte infusions following allogeneic transplant for pediatric hematologic malignancies.

The primary outcome is relapse at 2 years post-transplant, defined as >5 % blasts in bone marrow. The registry describes observation for patients with full donor chimerism and no evidence of MRD and an intervention group receiving immunosuppression withdrawal and donor lymphocyte infusions. Allocation is non-randomized, and the record cautions that the arms are not a like-for-like comparison.

Survival at 2 years post-transplant and acute and chronic GVHD incidence are listed as secondary outcomes. Primary and secondary outcome results are not reported in the registry record. The adverse-event entries include limited counts and a serious-event term, but do not support a complete comparative safety interpretation.