Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System (NCT00520130), a randomized phase 1, phase 2 study. The primary outcome is Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD).

2. Clinical Question

3. Trial Design

The registry classifies NCT00520130 as a randomized, parallel-group, unmasked phase I/II trial. Its recorded enrollment is 92. The study is listed as completed, with a start date of 2007-10-30 and a primary completion date of 2015-10-14. The sponsor is the National Cancer Institute (NCI).

The study addressed transplantation for people with advanced or high-risk cancers of the blood and immune system who did not have a suitable HLA-matched sibling donor. The official title describes targeted immune-depleting chemotherapy followed by reduced-intensity allogeneic hematopoietic stem cell transplantation using 8/8 and 7/8 HLA-matched unrelated donors. The brief summary says that all participants received chemotherapy before transplantation to treat the cancer and suppress immune function. It also describes evaluation of two different drug combinations for prevention of graft-versus-host disease (GVHD).

The randomized comparison was between the TMS regimen—tacrolimus, methotrexate, and sirolimus—and the cyclosporine arm, labeled AC in the arm description. The posted primary outcome is the percentage of participants with grade II–IV acute GVHD at 6 months. The registry also lists outcomes concerning more severe acute GVHD, toxicities, engraftment, survival, and treatment-related mortality.

The primary endpoint denominators are 39 in the TMS arm and 42 in the AC arm. The primary-outcome description notes that two of 44 patients who completed the AC arm were transplanted after the data-analysis cutoff and are not included. How those endpoint populations relate to all randomized participants, and the full participant flow through treatment and follow-up, are not reported in the registry record. The original sample-size justification and the trial's original statistical analysis plan are also 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.

Before assignment: There were 89 participants in the study. 3 patients enrolled and their cancers progressed prior to randomization so they were taken off study. 3 of these participants went back into remission with additional chemo and were re-enrolled on the protocol and randomized. They are counted twice in the enrolment (e.g. 92) but only once in the Started row.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

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.

Population: There were 89 participants in the study. 3 patients enrolled and their cancers progressed prior to randomization so they were taken off study. 3 of these participants went back into remission with additional chemo and were re-enrolled on the protocol and randomized. They are counted twice in the enrolment (e.g. 92) but only once in the Started row.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD), measured over 6 months.

The primary endpoint is the percentage of participants with grade II–IV acute graft-versus-host disease within 6 months. Acute GVHD is a complication involving an immune response against the transplant recipient. The registry says grading followed the 1994 Consensus Conference on Acute GVHD Grading criteria. The endpoint combines grade II, III, and IV events, so it represents a broader range of acute GVHD severity than an endpoint restricted to grade III–IV.

Reporting a percentage makes the observed event frequency comparable across arms with different denominators. The registry gives 42.0% in the TMS arm and 38.0% in the cyclosporine arm. Their 95% confidence intervals are 26.0% to 57.0% and 23.0% to 53.0%. Those intervals convey uncertainty about the underlying event percentages; they are not ranges containing a known proportion of individual participants.

This endpoint is relevant to the stated comparison because the trial evaluates two GVHD prophylaxis regimens after transplantation. It is not, by itself, a complete measure of the overall balance of benefits and harms, nor does it describe other outcomes such as survival, engraftment, or toxicity. Those outcomes require separate interpretation. The registry record identifies the assessment time as 6 months but does not report further detail about handling incomplete endpoint follow-up.

7. Results Posted in the Registry

• B - Cyclosporine (AC) Arm: 38.1% (16/42) versus 41.0% (16/39) on control; risk difference -2.9 percentage points (95% CI -24.2 to 18.4), risk ratio 0.93 (0.54–1.59); unadjusted two-proportion z-test p = 0.787.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • B - Cyclosporine (AC) Arm: 21.4% (9/42) versus 12.8% (5/39) on control; risk difference 8.6 percentage points (95% CI -7.6 to 24.9), risk ratio 1.67 (0.61–4.56); unadjusted two-proportion z-test p = 0.306.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B - Cyclosporine (AC) Arm and the control. The interval gives the range of effects that remain compatible with the data.

Toxicities

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • B - Cyclosporine (AC) Arm: 93.3% (42/45) versus 97.7% (43/44) on control; risk difference -4.4 percentage points (95% CI -12.9 to 4.1), risk ratio 0.96 (0.87–1.05); unadjusted two-proportion z-test p = 0.317.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B - Cyclosporine (AC) Arm and the control. The interval gives the range of effects that remain compatible with the data.

Early Treatment Related Mortality

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • B - Cyclosporine (C) Arm: 0.0% (0/42) versus 2.6% (1/39) on control; risk difference -2.6 percentage points (95% CI -7.5 to 2.4); unadjusted two-proportion z-test p = 0.296.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B - Cyclosporine (C) Arm and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address different aspects of GVHD, toxicity, engraftment, survival, and treatment-related mortality. Their overall pattern does not provide a uniformly precise comparison that changes the interpretation of the primary result. The more severe acute GVHD endpoint is directionally higher in the cyclosporine arm, while the posted comparison remains uncertain. Toxicity is reported in both adverse-event groups, and early treatment-related mortality counts are sparse. These outcomes have different definitions, denominators, and follow-up windows, so they should not be collapsed into one overall effect.

The secondary findings are related to the primary question because GVHD prophylaxis and transplant complications are part of the same treatment setting. But they do not simply confirm or overturn the grade II–IV acute GVHD result. The severe-grade endpoint is a subset of the primary severity range, while toxicity and mortality capture other outcomes. Engraftment and survival address still other clinical dimensions. Results for several listed secondary outcomes are not reported in the registry record.

Unadjusted secondary results carry less weight because the trial reports multiple outcomes and the registry does not report a multiplicity adjustment or a hierarchy for interpreting them. General statistical principle: when many hypotheses are tested, the chance of at least one apparently notable result due to random variation can increase. An isolated secondary p-value is therefore not equivalent to a single prespecified primary test. The registry lists 18 outcome measures, but does not describe a correction strategy or identify which secondary findings were intended to support confirmatory conclusions.

The secondary outcomes can still be useful descriptively. They show which outcome domains were tracked and provide context for the transplant experience recorded by the study. However, differences in outcome definitions, populations, and observation periods make broad claims across them inappropriate. A full assessment would require detailed analysis methods, participant-level follow-up information, and the complete results for all planned outcomes, which are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD)
• Toxicities
• Days to Engraftment of Neutrophils
• Days to Engraftment of Platelets
• Days to Engraftment of Lymphocytes
• Overall Survival
• Early Treatment Related Mortality
• Percentage of Participants With Late Treatment Related Mortality

9. Statistical Interpretation

10. Statistical Methods Explained

Statistical interpretation starts with the outcome definition and the groups being compared. The primary outcome is binary at the participant level: a participant either met the grade II–IV acute GVHD definition within 6 months or did not. The registry presents the event percentage in each arm, its 95% confidence interval, and an unadjusted comparison between arms.

What does a percentage describe?

A percentage describes the observed share of participants in an arm who experienced the specified event, using the listed arm denominator. It is a summary of the participants included in that particular endpoint analysis, not automatically of everyone enrolled or randomized. Here, the primary endpoint lists 39 participants in TMS and 42 in AC. The endpoint description specifically notes two AC-arm patients transplanted after the data-analysis cutoff were not included. Other details about the primary analysis population are not reported in the registry record.

Percentages are useful for describing event frequency, but they do not by themselves quantify how precisely the underlying frequency is known. That is why the registry also reports confidence intervals. Comparisons also need to account for uncertainty: two observed percentages can differ numerically even when the data do not clearly distinguish their underlying rates.

How should the confidence interval be read?

A 95% confidence interval is a statistical range constructed by a method that, under its assumptions, would cover the true underlying parameter in 95% of repeated samples. It does not mean there is a 95% probability that this particular interval contains the true value. Nor does it describe the range of outcomes for individual participants. In this trial, the primary confidence intervals are wide, signaling that the event percentages are estimated with limited precision.

What does the unadjusted comparison add?

The registry comparison is labeled a risk difference. In general, a risk difference expresses the difference between event proportions in two groups, with the sign depending on the order of subtraction. The posted unadjusted p-value for the primary comparison is 0.787. A p-value measures how unusual data at least as incompatible with a specified no-difference model would be if that model and the analysis assumptions held. It is not the probability that the no-difference model is true, and it does not measure the size or clinical importance of a difference.

An unadjusted comparison is not adjusted for other participant or clinical characteristics. Random allocation is intended to support a fair comparison, but an unadjusted result does not show whether baseline balance was achieved, and the registry record does not give a baseline table or adjusted primary analysis. The record also does not report a detailed statistical plan, so the prespecified status of this analysis and any planned covariate adjustments are not reported in the registry record.

Why distinguish endpoint severity and timing?

Grade II–IV acute GVHD and grade III–IV acute GVHD are related but distinct outcomes. The latter is limited to more severe grades and therefore has a different event frequency and a different statistical precision. The primary outcome is assessed at 6 months; the severe-grade secondary outcome is also assessed at 6 months. Neither should be substituted for the other when interpreting the trial question.

Other outcomes use different definitions and follow-up periods. Toxicities are recorded as participants with toxicities over a timeframe of 103 months and 22 days. Early treatment-related mortality is defined as occurring at or before 28 days after transplantation. Engraftment, survival, and late treatment-related mortality are also listed among secondary outcomes. These measures do not share a common denominator or time window by definition, and their estimates should not be compared as though they were repeated measures of the primary endpoint.

What can be concluded from a nonsignificant result?

General statistical interpretation: a large p-value does not establish equivalence, noninferiority, or no effect. Those conclusions require a design and analysis that specify an acceptable margin and assess uncertainty against that margin. Such a margin and analysis are not reported in the registry record. Here, the primary estimate is imprecise, so the data do not provide a precise answer about the difference between regimens.

Likewise, a small p-value would not by itself establish that a difference is clinically important. Statistical evidence, effect size, precision, outcome meaning, and study design all matter. This is especially relevant when many outcomes are examined: an isolated unadjusted result can arise by chance more readily across a collection of tests. The registry record does not report a multiplicity procedure.

Why do the endpoint denominators matter?

The primary analysis uses fewer participants than the recorded enrollment, and the registry gives a specific post-cutoff transplant explanation for two AC-arm patients. The record does not report whether all other enrolled participants were randomized, whether they received their assigned regimen, or how incomplete observations were treated. Without those details, readers should avoid assuming that the primary results are intention-to-treat estimates or that exclusions were unrelated to outcome. Those analysis-population details are not reported in the registry record.

11. Confidence Intervals and Precision

The primary estimates are 42.0% for TMS and 38.0% for cyclosporine. Their 95% confidence intervals extend from 26.0% to 57.0% and from 23.0% to 53.0%, respectively. These are broad intervals: the observed percentages are not precise estimates of a single underlying event frequency. The overlap is substantial, and the unadjusted comparison has p = 0.787. The posted results therefore leave considerable uncertainty about the direction and size of any underlying difference.

Confidence intervals should be interpreted as a measure of statistical precision, not as a guarantee that future participants will have outcomes within the interval. In general, greater precision produces a narrower interval, while limited information tends to produce a wider one. Precision depends on the amount and distribution of outcome information and on the estimation method. The registry record does not report enough methodological detail to assess all assumptions behind the intervals.

The primary denominator note also matters for precision and interpretation. The listed endpoint groups are 39 and 42 participants, and two AC-arm patients transplanted after the data-analysis cutoff are excluded according to the endpoint description. The record does not explain all population exclusions or report how missing outcome data were handled. Consequently, the intervals quantify uncertainty for the reported endpoint analysis, not necessarily for all enrolled participants.

A confidence interval that overlaps another arm's interval is not itself a formal test of the difference. The trial's unadjusted comparative result should be considered alongside the arm estimates and their uncertainty. Neither the intervals nor the p-value demonstrates equivalence; an equivalence conclusion would require an appropriate margin and design, which are not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial's original sample-size justification. The registry record does not report the original design assumptions or sample-size justification. These planning figures are participants per arm for the binary outcomes shown, not total event counts. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers an effect to detect expressed as a fraction of the observed effect.

The 80% power column describes the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column uses the same idea with a higher target chance of detection. Power is a planning property under assumed conditions; it is not the probability that the trial's conclusion is correct.

For the primary endpoint, planning for 100% of the observed effect gives 4,370 participants per arm for 80% power and 5,850 for 90% power. Planning for 75% of the observed effect gives 7,794 and 10,433 participants per arm. Planning for 50% of the observed effect gives 17,591 and 23,548 participants per arm. Smaller effects require more participants to detect under the same assumptions, which is why the figures increase as the effect fraction gets smaller.

These are not observed power estimates. They are hypothetical planning illustrations and should not be used to claim that the completed trial was adequately or inadequately powered without the original design rationale and a clearly specified target effect. The calculations also rely on assumptions that may not match the design or conduct of this complex transplantation trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.410; treatment proportion p₁ = 0.381; average p̄ = 0.396.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6915 = 1.3554.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6912 = 0.5817.
4. n = (1.3554 + 0.5817)² / (-0.0293)² = 4,369.7, rounded up to 4,370 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.41025641025641                          # control proportion
p1 <- 0.380952380952381                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(520130)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 4,370 (80% power), 5,850 (90% power)
 75% of observed effect: n per arm = 7,794 (80% power), 10,433 (90% power)
 50% of observed effect: n per arm = 17,591 (80% power), 23,548 (90% power)
power.prop.test: 4369.7 
Simulated power at n = 4,370 per arm: 0.804 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a broad set of outcomes, including acute GVHD at different severity thresholds, toxicities, engraftment, survival, and early and late treatment-related mortality. Examining multiple outcomes creates a multiplicity issue: even when there is no underlying difference, repeated testing can increase the chance of seeing one apparently unusual result. This is a general statistical concern, not evidence that any particular reported finding is false.

The registry record does not report a multiplicity adjustment, a hierarchy of secondary outcomes, or an analysis plan explaining how results across outcomes were to be interpreted. It also lists no reported analyses. The displayed unadjusted comparisons should therefore be treated as descriptive or exploratory rather than as a set of independently confirmatory findings. The original trial's statistical plan and any planned interim analyses are not reported in the registry record.

Missing-data and analysis-population details are also limited. The primary endpoint description says two of 44 AC-arm patients who completed that arm were transplanted after the analysis cutoff and are not included. The primary estimates use 39 TMS and 42 AC participants. The registry record does not provide a complete participant flow, explain all differences between these denominators and enrollment, state whether the primary analysis followed intention-to-treat, or describe how missing outcome observations were handled. It also does not report sensitivity analyses for incomplete follow-up.

These omissions matter because exclusions or incomplete outcome assessment can affect both the groups represented and the uncertainty of the estimates. Randomization supports comparison when the randomized groups are analyzed appropriately, but the registry record does not establish how the primary analysis population was constructed. Readers should interpret the posted results as estimates for the listed analysis groups, not assume that they represent every enrolled or randomized participant.

15. 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: infection with normal anc or grade 1 or 2 neutrophils::blood (46.7%), infection with normal anc or grade 1 or 2 neutrophils::lung (pneumonia) (28.9%), infection with normal anc or grade 1 or 2 neutrophils::catheter-related (26.7%), renal failure (22.7%), death not associated with ctcae term::disease progression nos (22.2%).

The adverse-event summary lists serious adverse events for 36 of 44 participants in the TMS group and 41 of 45 in the cyclosporine group. Other adverse events were recorded for 43 of 44 and 42 of 45, respectively. The registry separately lists 8 deaths in the TMS group and 19 in the cyclosporine group. These are group-level counts in the adverse-event record; the record does not establish that every death was caused by treatment or by an adverse event.

The more frequent listed serious-event terms include infection with normal ANC or grade 1 or 2 neutrophils at blood, lung (pneumonia), and catheter-related sites, as well as renal failure, disease progression NOS, and diarrhea. The reported percentages are attached to those listed terms; they should not be interpreted as mutually exclusive categories or added together. A participant may contribute to more than one event term, and the registry does not describe the detailed counting rules in the record.

These safety denominators differ from the primary GVHD endpoint denominators. The registry record does not explain the relationship between the adverse-event populations and the primary analysis populations. The figures describe reported events and participants, but do not by themselves establish comparative causality or provide adjusted safety comparisons.

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

The posted results answer a narrow question: what percentage of the listed analysis participants had grade II–IV acute GVHD within 6 months in each prophylaxis arm? The reported percentages are 42.0% with TMS and 38.0% with cyclosporine. The confidence intervals are broad, and the unadjusted comparison does not clearly distinguish the groups. This is evidence of uncertainty in the comparison, not proof that the regimens are equivalent.

The randomized contrast concerns prophylaxis regimens in the setting of chemotherapy and reduced-intensity allogeneic transplantation. It does not estimate the effect of transplantation versus no transplantation, chemotherapy versus no chemotherapy, or matched versus unmatched donors. Because the treatment setting involves several components, the primary comparison should not be attributed to any one component beyond the regimen contrast recorded by the trial.

The results also do not establish a conclusion about every listed secondary outcome. Those outcomes have different definitions and timeframes, and several results are not reported in the registry record. Unadjusted findings among multiple outcomes require caution, particularly without a reported multiplicity strategy or complete analysis plan. Safety counts are descriptive and should not be interpreted as proof that an event was caused by a particular regimen.

The participants described in the record had advanced or high-risk cancers of the blood and immune system and lacked a suitable HLA-matched sibling donor. Findings in this study context should not automatically be generalized to people with other conditions, donor situations, or transplant approaches. The registry record does not report enough detail about baseline characteristics, full participant flow, or missing outcome handling to assess all limits to generalization.

In practical statistical terms, the posted result is an imprecise comparison. It can inform understanding of the outcomes observed in this trial, but it does not establish a clinically meaningful advantage, equivalence, or absence of difference. Those conclusions would require appropriate definitions, adequate precision, and a fully described analysis framework.

17. Why This Trial Matters Statistically

This trial is statistically notable because it compares two GVHD prophylaxis strategies within a randomized transplantation study, where the primary question concerns a clinically important complication. Randomization is an important design feature for comparing groups, while the unmasked design and complex transplant setting make careful attention to outcome definitions, analysis populations, and uncertainty especially important.

The primary endpoint illustrates why an observed difference should not be interpreted without precision. The arm percentages are numerically different, but the confidence intervals are wide and the unadjusted comparison does not provide a clear separation. This is a useful example of the distinction between the direction of an observed estimate and the strength of evidence about an underlying difference. A nonsignificant comparison is not an equivalence result.

The record also highlights how denominator definitions shape interpretation. The primary endpoint has its own analysis population and a specific cutoff-related exclusion note, while adverse-event summaries use other denominators. Without a full participant flow and missing-data description, readers cannot assume that all outcomes describe the same population or that all randomized participants were included in each analysis.

Finally, multiple outcome domains make transparent statistical planning important. The registry does not report the original analysis plan or multiplicity approach, so secondary findings should be considered in context rather than elevated individually. The study demonstrates why registration details, complete outcome reporting, and explicit analysis methods are central to responsible interpretation of complex clinical trials.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The trial concerns a clinically and biologically varied population. The registry lists myelodysplastic syndrome, Hodgkin's lymphoma, non-Hodgkin's disease, acute leukemia, and multiple myeloma, among other descriptions of blood and immune system cancers. The record does not provide condition-specific outcome estimates, so the posted overall results do not show whether outcomes differed across these diagnoses.

The transplant approach also includes several components: targeted immune-depleting chemotherapy, reduced-intensity conditioning, allogeneic transplantation, and GVHD prophylaxis. The randomized comparison is between prophylaxis regimens, not between the full transplant approach and an alternative without transplantation. Donors are described as unrelated and 8/8 or 7/8 HLA-matched, but the registry does not provide outcome estimates by donor match category.

The study was unmasked, and the primary endpoint is a graded clinical outcome. The registry identifies the grading criteria but does not report whether outcome assessment was blinded or how disagreements were resolved. Its primary analysis population excludes two AC-arm patients transplanted after the data-analysis cutoff; other population and missing-data details are not reported in the registry record.

Precision is limited for the primary comparison, and the record does not report an original sample-size justification, a full statistical analysis plan, or a multiplicity strategy. The posted secondary results are therefore difficult to interpret as confirmatory evidence. The registry also lists outcomes for which results are not reported in the registry record. These limitations constrain conclusions about subgroup patterns, robustness, and the overall balance of outcomes.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System — NCT00520130.
• Registry record last updated 2019-03-05; status last verified 2019-02.
• Results first posted 2017-08-24.
• 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.

22. Record Summary

NCT00520130 is a completed randomized, parallel, unmasked phase I/II study sponsored by the National Cancer Institute. It compared TMS and cyclosporine GVHD prophylaxis regimens after chemotherapy and reduced-intensity allogeneic stem cell transplantation for people with advanced or high-risk blood and immune system cancers without a suitable HLA-matched sibling donor.

The primary endpoint was grade II–IV acute GVHD at 6 months. The posted arm percentages were 42.0% for TMS and 38.0% for cyclosporine, with broad 95% confidence intervals and an unadjusted p-value of 0.787. The registry record notes a post-cutoff transplant exclusion in the AC arm. Secondary outcomes include more severe acute GVHD, toxicities, engraftment, survival, and treatment-related mortality. Several design, analysis-population, missing-data, and multiplicity details are not reported in the registry record.