Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine (NCT00595127), a na na study. The primary outcome is Incidence & Quality of Engraftment & Hematopoietic Reconstitution.

2. Clinical Question

In clinical terms, the study was intended to examine whether selected stem cells could take and grow after the described conditioning approach, whether those cells could engraft without graft-versus-host disease, and what side effects occurred. The registry lists 21 participants enrolled and describes the trial as completed. Those details establish the scale and status of the study, but they do not establish how many participants engrafted, how engraftment was assessed, or what happened to individual participants over follow-up.

Because the trial has no control group, its primary question is a descriptive one: what outcome was observed in this group under the study approach? It cannot, by itself, estimate how outcomes would have differed under another treatment or without the intervention. The mismatch between the stated transplant focus and the arm description also limits certainty about which intervention the record attributes to participants.

3. Trial Design

The registry describes a completed, single-group pilot trial sponsored by Memorial Sloan Kettering Cancer Center. Its enrollment is 21, its allocation is listed as NA, and its masking is NONE. The phase is listed as NA. These registry fields describe a study without a randomized allocation or a masked comparison. The start is recorded as 2001-06 and primary completion as 2013-05.

The title concerns hematopoietic stem-cell transplantation for patients with Fanconi anemia who lack a genotypically identical donor, using total body irradiation, cyclophosphamide and fludarabine. The listed interventions are cyclophosphamide, fludarabine and total body irradiation. The brief summary describes low-dose total body irradiation and cyclophosphamide with fludarabine, and says the study was intended to assess stem-cell engraftment, graft-versus-host disease and side effects.

There is an important inconsistency in the record: its arm description calls the study open-label and single-arm but describes an intravenous 131I-8H9 injection preceded by unlabeled 8H9. That description does not match the transplant-focused title and listed interventions. The record does not explain the discrepancy, so the arm description should not be silently treated as a detailed account of the transplant regimen.

A control group, random allocation, and a direct treatment comparison are not reported. The protocol, eligibility criteria beyond the stated donor circumstance, participant characteristics, and details of treatment delivery are not reported in the registry record. The sample-size justification and any interim-analysis plan are also not reported in the registry record. The pilot designation and enrollment describe the study but do not supply those missing design details.

With a single group, the study can describe outcomes among enrolled participants if outcome data are available. It cannot separate effects of the study approach from other influences through a concurrent control comparison. In this record, the primary outcome result is not reported, so even a descriptive estimate of engraftment cannot be stated.

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:

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 Incidence & Quality of Engraftment & Hematopoietic Reconstitution, measured over 8 years.

The primary outcome is titled “Incidence & Quality of Engraftment & Hematopoietic Reconstitution.” Its measure is the number of patients who engrafted, with participants as the unit and an 8 years timeframe. This is a count endpoint: it is intended to record how many participants experienced the specified event rather than to report a continuous measurement.

Engraftment is relevant to the stated purpose because the study aimed to determine whether selected stem cells could take and grow after transplantation. Hematopoietic reconstitution is also named in the outcome title, indicating an interest in recovery of blood-forming function. However, the registry description of the measure says only “Number of patients who engrafted.” It does not define criteria for engraftment, specify how its quality was assessed, or explain how reconstitution was incorporated into the count. Those details are not reported in the registry record.

A count can be useful for describing whether the event occurred in the study group. For interpretation, a count needs a clear denominator and a defined assessment period; the record gives enrollment of 21 and an outcome timeframe of 8 years, but does not report the primary outcome count. Consequently, the observed proportion, uncertainty around the outcome, and any comparison with a prespecified target cannot be described from this record.

In general, an endpoint is most informative when its definition and assessment rules are clear before outcomes are interpreted. The registry’s broad outcome title and brief measure description leave uncertainty about what constituted engraftment and how the title’s reference to quality was operationalized.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are easiest to interpret when the outcome definition, analysis population, comparison, and uncertainty measure are all clear. The registry record gives some design and outcome metadata, but it does not report a primary-outcome analysis. The explanations below distinguish general statistical principles from details documented for this trial.

What does a single-group design estimate?

In general, a single-group study can describe outcomes among the participants who receive the study approach. For a binary event such as engraftment, an analysis might report the number with the event and the number assessed. The event count is the numerator; the assessed participants form the denominator. A confidence interval can express uncertainty around an estimated event frequency. The registry record reports enrollment of 21 but does not report the engraftment count, the number assessed for the endpoint, or a confidence interval.

Without a concurrent comparison group, a single-group study cannot directly estimate a treatment difference against a control. Even if an event frequency were available, it would describe this group rather than establish what would have happened to comparable participants under another approach. This is a design limitation, not a problem that can be resolved simply by choosing a different statistical test.

What does the primary outcome description tell us?

The recorded primary measure is a number of patients who engrafted, and the timeframe is 8 years. The title also refers to the quality of engraftment and hematopoietic reconstitution. General statistical practice requires operational definitions for such outcomes: the criteria for counting an event, the time at which it is assessed, and the handling of participants without an assessment. These definitions are not reported in the registry record. The record therefore does not support a judgment about whether an analysis would have captured the full outcome concept in the title.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the method. Its width reflects statistical uncertainty; it does not account for every possible source of bias, such as unclear outcome definitions or incomplete follow-up. No confidence interval for engraftment is reported in the registry record. A p-value, if available, would address compatibility with a specified statistical null hypothesis, not the size or clinical importance of an outcome. No primary-outcome p-value or hypothesis test is reported.

For binary outcomes, methods may differ in their assumptions and in how they behave with small samples or sparse events. General methods can use exact calculations or approximations, but an appropriate choice depends on the prespecified question and data structure. The registry record does not report a statistical analysis plan, the method used for the primary endpoint, or any model assumptions. It is therefore not possible to attribute a particular inferential method to the trial.

What do the sample-size assumptions mean?

The registry describes sample-size figures as planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such figures are planning illustrations, not observed power. They do not establish that the trial was designed with those assumptions, and the record explicitly distinguishes them from the trial’s own design. The hypothetical two-arm equal-allocation setup also does not match the registry’s single-group design. The trial’s sample-size justification is not reported in the registry record.

In general, sample-size planning depends on the outcome, the effect the design is intended to detect, the chosen error rates, allocation, and analysis method. An illustration based on an observed effect is especially dependent on that effect estimate and should not be read as evidence that a study had a particular probability of finding a result. No observed primary effect is reported in the registry record, so the underlying outcome estimate cannot be independently interpreted from the record.

What can safety summaries show?

Safety summaries count participants or events according to the registry’s reporting categories. They can describe what was recorded in the study group, but they do not by themselves establish that a treatment caused an event. In general, event counts and percentages need clear definitions, denominators, and rules about whether a participant can contribute more than one event. The serious-event terms in the record are percentages, but the registry does not explain their calculation or provide event-level details. Their interpretation should therefore remain descriptive.

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("Cyclophosphamide and Fludarabine")
n      <- c(21)
events <- c(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  Cyclophosphamide and Fludarabine  21  19  90.5  69.6  98.8  71.1  97.3  70.8  97.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analyses. It does not report whether the primary outcome was tested using a formal hypothesis, whether secondary outcomes were analyzed, or whether multiple comparisons were planned. The protocol and statistical analysis plan are not reported in the registry record. Without that information, it is not possible to determine whether multiplicity was addressed or how any statistical significance threshold would have been applied.

In general, multiplicity arises when researchers evaluate several outcomes, timepoints, subgroups, or statistical comparisons. Repeated testing can increase the chance of at least one apparently notable result under a null hypothesis. Prespecified testing strategies can manage that issue, but no such strategy is described in the registry record. The record’s single listed outcome measure does not establish that no other outcomes were assessed; it only describes what is registered in the available outcome information.

The record does not report missing primary-outcome data, the number of participants assessed at the endpoint, or how participants lost to follow-up were handled. It also does not describe an analysis population, such as whether the analysis included all enrolled participants or only those with an evaluable outcome. These details are not reported in the registry record. In general, missing outcomes can affect an event count and may bias an estimate if the likelihood of missingness is related to the outcome or participant status. The direction and size of any such effect cannot be determined without information about missingness and the analysis approach.

Because the outcome timeframe is 8 years, clarity about follow-up and endpoint ascertainment would be important for understanding who contributed to the result. The registry does not report those details, and no primary-outcome result is available to assess. There is therefore no basis in the registry record for reconstructing multiplicity adjustments, missing-data methods, or analysis-population rules.

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: hypoxia (9.5%), cardiovascular, other (4.8%), diarrhea (peds/bmt) (4.8%), dyspnea (4.8%), hemorrhage, other (4.8%).

The registry’s safety group is titled Cyclophosphamide and Fludarabine. It lists 21 participants at risk for serious adverse events and 5 participants affected. For other adverse events, it lists 21 at risk and 21 affected. These are participant counts as recorded; they should not be treated as a comparison between treatment groups because the study is registered as single-group.

The listed serious adverse-event terms are Hypoxia at 9.5%, Cardiovascular, other at 4.8%, Diarrhea (PEDS/BMT) at 4.8%, Dyspnea at 4.8%, Hemorrhage, other at 4.8%, and Infection w.out neutropenia at 4.8%. These are the reported percentages, not independently calculated rates. The registry does not specify whether a participant could appear under more than one term, the time period for these summaries, or the precise denominator used for each term.

In general, a serious adverse event is a safety reporting category, not proof that an intervention caused an event. These summaries describe events recorded in the study group; they do not establish comparative risk or attribute causation. The record also does not report event timing, participant-level details, or a control group. The mismatch between the transplant-focused description and the arm description referring to 131I-8H9 is relevant when interpreting which treatment the safety group represents.

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

The registry establishes that a completed, single-group pilot study enrolled 21 participants and registered engraftment as its primary outcome, with a timeframe of 8 years. It also records selected adverse-event summaries. These details describe the study’s scope and the kinds of outcomes it intended to monitor.

The primary result itself is not reported in the registry record. There is no engraftment count or reported estimate of its quality, no confidence interval, and no primary-outcome analysis. As a result, the registry information cannot answer how many participants engrafted or how precisely an outcome frequency was estimated. Completion status does not substitute for outcome data.

Even with a reported result, the single-group design would support a description of outcomes among participants rather than a direct comparison with another approach. General statistical interpretation distinguishes an observed event frequency from a causal treatment effect: estimating a causal contrast requires a suitable comparison and assumptions that the study record does not establish. The absence of random allocation and a control group means the record does not provide a like-for-like treatment comparison.

The safety entries can be read as descriptive counts and terms in the registry’s designated group. They do not show whether events were caused by treatment, and the absence of a comparator prevents a direct comparative safety estimate. The record does not provide enough detail to reconstruct event timing or the calculation of each listed percentage.

Finally, the arm description conflicts with the transplant-focused title and intervention list by referring to 131I-8H9 and unlabeled 8H9. The registry does not explain this discrepancy. That uncertainty, combined with the absent primary outcome result and limited analysis details, means the record is informative about the registered study aims and design but insufficient to draw a conclusion about engraftment outcomes.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a registered research question and a reported result. The record names engraftment as the primary outcome and gives a timeframe, but does not report the event count or an analysis. A study can be marked completed without the registry record containing the outcome information needed to quantify its primary finding.

The design also illustrates the limits of descriptive evidence. A single group can provide information about outcomes among participants, but a treatment comparison requires a comparator. Without one, observed outcomes cannot be directly contrasted with outcomes under another approach. This distinction matters when readers encounter an outcome label or safety count and are tempted to interpret it as evidence of comparative effectiveness or harm.

The record’s sample-size assumptions are another useful distinction: the described planning illustrations use a hypothetical two-arm setup, while the registered study is single-group. Those illustrations are not the trial’s own design or observed power. They should not be used to infer that the study was powered for its registered primary outcome.

Finally, the discrepancy between the transplant focus and the arm description demonstrates why consistency across registry fields matters. Clear alignment among the trial title, interventions, arm description, outcomes, and analysis plan helps readers understand what was studied and how to interpret results. Here, the record leaves that alignment unresolved. Statistical interpretation must therefore account not only for sample size and design, but also for whether the treatment and outcome descriptions are sufficiently clear.

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 for interpreting outcomes is that the registry does not report the primary engraftment count or an analysis. It also does not report a confidence interval, test result, or analysis population. The enrollment of 21 provides context for the study’s size but cannot replace the missing endpoint result.

The study is registered as single-group, with allocation listed as NA and masking listed as NONE. No concurrent control group is reported, so the record cannot support a direct comparative estimate. The sample-size justification and statistical analysis plan are not reported in the registry record; neither are interim analyses, endpoint assessment criteria, or the handling of missing outcome data.

The outcome description is incomplete for interpreting the title’s full scope. It identifies a count of patients who engrafted over 8 years, while the title also refers to quality of engraftment and hematopoietic reconstitution. The record does not define those concepts or specify assessment rules. Follow-up and participant-level outcome ascertainment are also not reported.

There is a notable inconsistency between the transplant-centered title and intervention list and the arm description referring to an intravenous 131I-8H9 injection preceded by unlabeled 8H9. The registry does not explain the discrepancy. This makes it harder to identify what the arm description is intended to represent and to connect it confidently to the trial’s stated question.

The safety information is limited to summary counts and listed serious-event terms with percentages. The record does not report event timing, severity-grading procedures, whether participants could contribute multiple terms, or a control group. These limitations constrain interpretation of both the primary outcome and safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine — NCT00595127.
• Registry record last updated 2016-08-10; status last verified 2016-06.
• Results first posted 2016-08-10.
• 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 describes a completed pilot study sponsored by Memorial Sloan Kettering Cancer Center, with 21 participants enrolled. It is listed as a single-group study with no masking and allocation recorded as NA. The title and listed interventions concern transplantation for patients with Fanconi anemia using total body irradiation, cyclophosphamide and fludarabine.

The primary outcome is the number of patients who engrafted, with a timeframe of 8 years. The outcome count and primary analysis are not reported in the registry record. The record lists serious adverse events in 5 of 21 participants at risk and other adverse events in 21 of 21 participants at risk, along with serious-event terms and percentages.

The arm description refers instead to 131I-8H9 and unlabeled 8H9; the registry does not explain this discrepancy. A control group, analysis plan, missing-data approach, and sample-size justification are not reported in the registry record. The available information therefore describes the study’s registration and selected safety summaries but does not provide its primary engraftment result.