High Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin's Lymphoma or Central Nervous System (CNS) Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for High Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin's Lymphoma or Central Nervous System (CNS) Lymphoma (NCT01182415), a na phase 2 study. The primary outcome is Proportion of Patients With CNS Involvement by B-cell NHL, Relapsed PCNSL, or Relapsed PIOL Who Are Alive and Progression-free at One Year.

2. Clinical Question

3. Trial Design

This was a phase II, single-group clinical trial sponsored by Massachusetts General Hospital. The registry lists enrollment of 30 and a completed study status. The recorded study start is 2010-06, and primary completion is listed as 2015-12. The study title describes high-dose thiotepa, busulfan, cyclophosphamide, and rituximab with autologous stem cell transplantation for patients with central nervous system involvement by non-Hodgkin’s lymphoma or primary central nervous system lymphoma.

The intervention combined high-dose chemotherapy with transplantation of the participant’s own stem cells. In the study summary, thiotepa, busulfan, and cyclophosphamide form the conditioning regimen, while rituximab was added to that regimen and to stem cell mobilization. Cytarabine is described as a standard mobilization drug. The registry lists autologous stem cell transplant as a procedure and high-dose chemotherapy as a drug intervention. Specific treatment doses, schedules, and eligibility details beyond those described are not reported in the registry record.

There was no randomized allocation, and masking is listed as none. Because all participants were in one treatment group, the design can describe outcomes among participants receiving the regimen but cannot directly compare those outcomes with a concurrent control group. The registry record does not report a protocol-defined historical control or other comparator. It also does not report the rationale for the planned enrollment or the statistical justification for the study size.

The registry lists four outcome measures, including the primary one-year alive-and-progression-free endpoint, two-year progression-free survival, two-year overall survival, and response rate. The primary endpoint description gives a one-year outcome, while its listed timeframe is 3 years. How that timeframe relates to assessment or follow-up is not reported in the registry record. The actual primary endpoint result and results for the listed secondary outcomes are also not reported.

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:

Analysis population for the primary outcome, as defined in the registry: The participant that was lost to follow-up was not available for analysis.

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 Proportion of Patients With CNS Involvement by B-cell NHL, Relapsed PCNSL, or Relapsed PIOL Who Are Alive and Progression-free at One Year, measured over 3 years.

The primary endpoint is the proportion of patients in the specified central nervous system lymphoma groups who are alive and progression-free at one year. It combines two clinically important conditions at a defined assessment point: the participant must be alive, and the disease must not have progressed. A participant who has died or whose disease has progressed by that point would not meet the endpoint definition. The registry defines relapse according to standard primary central nervous system lymphoma criteria using clinical and MRI criteria.

A proportion is a binary-outcome summary: each participant either meets the endpoint definition or does not. It can communicate the frequency of a defined outcome in the studied group, but it does not by itself show how outcomes compare with another treatment. In a single-group study, interpretation also depends on the population included in the analysis and how missing outcome information is handled.

The registry’s endpoint description specifies assessment at one year, while the listed timeframe is 3 years. That difference is recorded but not explained. The registry record does not report the number meeting the primary endpoint, the denominator analyzed, an estimated proportion, or a confidence interval. Consequently, the endpoint’s observed value and its precision cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry’s primary outcome is a binary endpoint: each participant is classified according to whether they were alive and progression-free at one year. The outcome is expressed as a proportion, meaning the number meeting the definition relative to the number included in the analysis. No primary outcome count, analyzed denominator, estimated proportion, or confidence interval is reported in the registry record, so no numerical estimate can be interpreted.

What does a proportion describe?

In general, a proportion summarizes how often a defined event or status occurs in an analyzed group. It is important that the numerator and denominator refer to the same outcome definition and analysis population. Here, the outcome definition requires both survival and absence of progression at the specified time point. The registry description says relapse was assessed using standard primary central nervous system lymphoma criteria based on clinical and MRI criteria. Further detail about assessment timing, adjudication, or the analysis rules is not reported in the registry record.

A confidence interval, in general, describes statistical uncertainty around an estimated quantity under the assumptions of the method used. It is not a guarantee that the true value lies within a particular interval, and it does not address limitations such as a missing comparator or biased outcome ascertainment. No confidence interval for the primary endpoint is reported in the registry record. The result’s precision therefore cannot be evaluated from the posted information.

How does the single-group design affect interpretation?

In general, a single-group study can describe outcomes observed among participants receiving an intervention. It does not directly estimate a difference between that intervention and a concurrent alternative. Outcomes may reflect the treatment as well as participant characteristics, disease course, follow-up, and other factors. Randomization is one way a comparative trial can balance factors across groups, but this study is not randomized and has no control group listed. The registry record does not describe a planned external or historical comparison.

The study is identified as phase II, but that label alone does not specify the statistical design, the decision threshold, or the evidence required for a conclusion. Those details are not reported in the registry record. No statistical analysis entries are listed, and a formal analysis plan, interim analyses, and stopping rules are not reported. They should not be inferred from the phase designation.

What do the planning assumptions mean?

General sample-size calculations estimate the amount of information a hypothetical study may need under specified assumptions. The record’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. For time-to-event outcomes, the illustration is described as reporting total events using the Schoenfeld approach; for other outcomes, it reports participants per arm. Such quantities are planning illustrations, not observed power and not a description of the actual single-group study’s enrollment plan. The registry does not report the original sample-size justification.

In general, a two-sided significance level defines how a hypothetical test treats departures in either direction under its null model. Equal allocation describes a planned balance between two groups. A normal approximation is a mathematical method for estimating a sampling distribution. These assumptions do not turn a single-group study into a two-arm comparison, and they do not establish that the trial had a particular probability of detecting an effect. The posted primary outcome result is absent, and the record does not identify the original planning assumptions.

Why do time-to-event methods need additional detail?

The registry lists two-year progression-free survival and two-year overall survival as secondary outcomes. In general, time-to-event analyses use information about when an event occurs and can account for participants whose event has not been observed by the end of follow-up, subject to specified censoring rules. The choice of event definition, follow-up, censoring, and estimator affects interpretation. Those analysis details and the results for these secondary outcomes are not reported in the registry record. The primary endpoint is described as a proportion at one year, so it should not automatically be treated as identical to a time-to-event analysis.

For a binary outcome, extra variation beyond that expected under a simple probability model is sometimes called over-dispersion. In general, it can make uncertainty larger than a basic model suggests. Whether over-dispersion is relevant depends on the design and analysis; no such modeling approach is reported for this study. No adjusted analysis, subgroup analysis, or model specification is reported either. These methods cannot be assumed from the outcome labels alone.

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("High-dose Chemotherapy With Autologous Stem Cell T")
n      <- c(29)
events <- c(28)
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  High-dose Chemotherapy With Autologous Stem Cell T  29  28  96.6  82.2  99.9  82.8  99.4  82.8  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and three secondary outcomes: two-year progression-free survival, two-year overall survival, and response rate. The primary endpoint is the proportion alive and progression-free at one year. The actual results for these outcomes are not reported in the registry record, and no statistical analysis entries are listed. A plan for prioritizing outcomes or controlling the chance of misleading findings when considering multiple outcomes is not reported.

In general, multiplicity arises when several outcomes, time points, or analyses are considered. If each is interpreted as a separate test, the chance of at least one apparently unusual result can differ from the chance associated with a single planned test. A prespecified strategy can clarify which findings are primary and how other findings should be interpreted. The registry identifies a primary outcome, but details of any multiplicity procedure are not reported. No adjustment method or hierarchy should be inferred.

The endpoint population description says that the participant lost to follow-up was not available for analysis. The registry does not report the primary endpoint denominator, the reason for loss to follow-up, or how missing information was otherwise handled. It does not describe imputation, sensitivity analyses, censoring rules for the primary endpoint, or a complete-case or intention-to-treat analysis population. Those methods are not reported in the registry record.

Missing outcome information can matter because the observed participants may not represent all enrolled participants. In general, analysis assumptions about missingness affect how a result should be interpreted. Without the outcome count, denominator, and missing-data methods, the extent and possible influence of missing information cannot be assessed. The registry record also does not report whether any planned interim analyses were conducted.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: anemia (6.7%), platelet count decreased (6.7%), febrile neutropenia (3.3%), gait disturbance (3.3%), mucositis oral (3.3%).

The safety summary lists 30 participants at risk in the high-dose chemotherapy with autologous stem cell transplant group. It records 6 participants with serious adverse events, 0 with other adverse events in the reported category, and 3 deaths. These counts describe the registry’s safety summary; they are not comparative effects because no control group is listed.

The registry also lists serious-event terms and percentages: anemia, 6.7%; platelet count decreased, 6.7%; febrile neutropenia, 3.3%; gait disturbance, 3.3%; mucositis oral, 3.3%; and lung infection, 3.3%. These are the reported terms and percentages, not a complete account of every clinical event or its course. The registry does not report the timing, duration, or treatment relationship for each event in this summary.

The 3 deaths should be interpreted as deaths recorded in the safety summary, not as deaths attributed to the regimen. Their causes, timing, and relationship to treatment are not reported in the registry record. Serious adverse-event counts likewise do not establish causation. Without a comparator, differences in safety relative to another treatment cannot be estimated from these data.

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

The study addresses a difficult-to-treat disease setting described in the registry: lymphoma involving the central nervous system. Its treatment strategy combined high-dose chemotherapy and autologous stem cell transplantation, with rituximab added to mobilization and conditioning as described in the study summary. The primary question focused on being alive and progression-free at one year.

The posted information does not include the primary endpoint result or results for the listed secondary outcomes. It therefore does not show the observed one-year proportion, how precise an estimate might be, or how outcomes developed over the listed follow-up periods. The safety summary provides counts and selected serious-event terms, but lacks a comparator and details about the timing or treatment relationship of events and deaths.

Even if an outcome estimate were available, this single-group design would describe participants in the study rather than directly establish a difference from another treatment. A comparison requires an appropriate reference group and methods that account for differences between groups. The registry record does not list a randomized or other concurrent comparator, and no historical comparison plan is reported.

These limitations do not make the study description uninformative: it identifies the treatment approach, intended population, endpoint, and safety counts. They do define what can be concluded from the posted information. The registry record does not support a numerical conclusion about the primary outcome, a comparative estimate of benefit or harm, or a claim about treatment causation. The study’s completion status and enrollment do not substitute for outcome results.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary question is expressed as a clearly defined one-year status: participants must be alive and progression-free. Such a binary endpoint can be understandable, but its interpretation depends on the exact population analyzed, the numerator and denominator, the assessment rules, and uncertainty around the estimate. The registry record does not report the primary result or the analyzed denominator, so those elements cannot be evaluated.

The design also highlights the distinction between describing an outcome and estimating a treatment contrast. A single-group study can report what happened among participants who received the regimen. It does not provide a randomized comparison with an alternative treatment. That distinction matters even if a proportion appears clinically interpretable: without a concurrent comparator, it cannot by itself show how the outcome differs from what would have happened under another approach.

The registry lists several outcomes and a planning illustration based on a hypothetical two-arm design. The actual study, however, is recorded as single-group. This illustrates why planning assumptions must be separated from the design actually conducted. The sample-size illustrations are planning aids, not observed power, and they are not the study’s own reported justification.

Finally, the record includes safety counts but does not report their timing, causes, or treatment relationships. Descriptive counts can identify events recorded during a study, but they do not establish causation or comparative safety. Together, the missing efficacy results, absent comparator, and limited analysis detail define the statistical boundaries of what can be learned from this registry record.

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 direct limitation is that the primary endpoint result is not reported in the registry record. The record therefore does not give the number of participants who were alive and progression-free at one year, the denominator analyzed, or a measure of uncertainty. Results for the listed secondary outcomes are also not reported. Without these results, outcome magnitude and precision cannot be assessed.

The single-group design has no randomized comparator. Outcomes cannot be used to estimate a treatment contrast against another regimen, and differences from an external group cannot be assessed because no such comparison is described. The registry lists enrollment of 30, but does not report the original sample-size justification or the statistical assumptions used to plan enrollment.

The primary endpoint description specifies one year, while the listed timeframe is 3 years. The registry record does not explain this difference. It also says that the participant lost to follow-up was unavailable for analysis, but does not provide the analyzed denominator, missing-data method, or sensitivity analysis. The record does not report detailed endpoint assessment procedures beyond the stated clinical and MRI criteria for relapse.

Statistical analysis entries are not listed. Details such as confidence intervals, model specifications, analysis populations, multiplicity handling, and any interim analyses are not reported. The safety summary gives selected event counts and terms, but does not report the timing or cause of deaths or whether events were considered treatment-related. These limitations restrict both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: High Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin's Lymphoma or Central Nervous System (CNS) Lymphoma — NCT01182415.
• Registry record last updated 2023-04-06; status last verified 2023-03.
• Results first posted 2017-12-29.
• 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 record describes a completed phase II, single-group study sponsored by Massachusetts General Hospital, with enrollment of 30. The recorded start is 2010-06 and primary completion is 2015-12. The intervention was high-dose chemotherapy with autologous stem cell transplantation; the study title specifies thiotepa, busulfan, cyclophosphamide, and rituximab.

The primary endpoint was the proportion of specified patients alive and progression-free at one year. The registry also lists two-year progression-free survival, two-year overall survival, and response rate. The primary and secondary outcome results are not reported in the registry record. One participant lost to follow-up was unavailable for analysis, but the analyzed denominator and missing-data methods are not reported.

The safety summary records 6 participants with serious adverse events, 0 with other adverse events in the reported category, and 3 deaths among 30 at risk. The study has no listed comparator and no masking. Statistical analysis details and the original sample-size justification are not reported.