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The design of phase III palliative chemotherapy trials in head and neck cancer.

This paper describes a series of 2447 patients with squamous carcinoma of the head and neck treated personally over 22 years; 276 patients with advanced untreatable disease and 498 with recurrent untreatable disease are analysed. The median survival for the first group was 13 weeks and for the second 11 weeks. The data fitted an exponential curve. Prognostic factors included general condition and N status for the first group, and site of the primary tumour, site of the recurrence and length of time to recurrence for the second group. However, these factors only explained 5% of the variance; the remaining 95% was unexplained, emphasizing the futility of stratification for prognostic factors, and the necessity for large trials. Using the above facts the number of patients required for a trial, and the length of the trial, can be worked out, and tables of these are given.

Aged↗

Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris.

The prognostic significance of exercise testing was compared with clinical and electrocardiographic (ECG) variables in a prospective study of 107 patients with unstable angina discharged from the hospital on medical therapy. During a follow-up period of 12.8 +/- 1.4 months, 10 patients (9%) had a nonfatal myocardial infarction (n = 8) or died (n = 2) and 22 (20%) were readmitted with recurrent unstable angina. The relation between 20 clinical, ECG and exercise test variables and the risk of adverse outcome (death, nonfatal myocardial infarction or recurrent unstable angina) was analyzed using both univariate and multivariate (logistic regression) analysis. Univariate predictors of adverse outcome included diabetes mellitus, evolutionary T wave changes, T wave changes on the preexercise ECG and low maximal rate-pressure product during exercise. Independent predictors of adverse outcome in multivariate analysis included diabetes mellitus, evolutionary T wave changes after admission, rest pain during hospitalization, ST depression during exercise and low maximal rate-pressure product. A predictive model constructed using the regression equation and all independent predictors stratified patients into high and low risk groups (41% and 5% risk of adverse outcome, respectively). The result of a predischarge exercise test adds independent prognostic information to clinical and ECG data in medically treated patients with unstable angina and could be used in combination with clinical and ECG data to identify patients at risk of adverse events.

Angina, Unstable↗

Extranodal nasal type NK/T-cell lymphoma: elucidating clinical prognostic factors for risk-based stratification of therapy.

The purpose of this study was to define distinctive clinical features of "nasal" and "nasal-type" NK/T cell lymphomas by assessing prognostic factors. The anatomic definition of extranasal NK/T cell lymphoma has been vague resulting in variable definitions of extranasal sites by different groups. We analysed the clinical behavior of 90 NK/T cell lymphoma patients and attempted to elucidate the prognostic factors for risk-based stratification of therapy. We observed no significant difference between "nasal" and "nasal-type" NK/T cell lymphomas in regards to clinical features and survival using the conventional anatomic classification. We suggest the categorisation of the two subtypes of NK/T cell lymphoma as follows: UNKTL (upper aerodigestive tract NK/T cell lymphoma) including all lymphomas confined to nasal cavity, nasopharynx, and the upper aerodigestive tract and EUNKTL (extra-upper aerodigestive tract NK/T cell lymphoma) group to include all sites other than the UNKTL group. The EUNKTL group in this study had advanced stage at diagnosis, higher LDH, higher IPI score, poorer performance and inferior response to the anthracycline-based chemotherapy with statistical significance. There was a significant difference in survival rate between EUNKTL and UNKTL group (20.0%, 54.0%, respectively, P = 0.0068). More aggressive treatment should be sought for this particular group of patients for EUNKTL patients.

Adult↗

Cardiopulmonary exercise testing identifies low risk patients with heart failure and severely impaired exercise capacity considered for heart transplantation.

OBJECTIVES: The 3-year survival rates of 500 patients with congestive heart failure (CHF) referred for heart transplantation were assessed to evaluate the clinical and exercise variables most useful for estimating prognostic risk. BACKGROUND: Detailed prognostic risk stratification of patients with a peak exercise oxygen consumption (VO2) < or = 14 ml/min per kg to identify lower risk patient subsets has been limited in earlier series by relatively small sample size. METHODS: Cardiopulmonary exercise testing was performed in 500 patients with CHF referred for heart transplantation; 154 (31%) had a peak exercise VO2 < or = 14 ml/min per kg. Univariate and multivariate analyses were performed to identify the 3-year prognostic risk. RESULTS: The 55% 3-year survival rate of the 77 patients with a peak exercise VO2 < or = 14 ml/min per kg unable to reach a peak exercise systolic blood pressure (SBP) of 120 mm Hg was significantly lower than the 83% survival rate in the 74 patients able to reach this exercise blood pressure (p = 0.004). Multivariate analysis revealed that peak exercise SBP (p = 0.0005) and percent predicted peak VO2 < or = 50% (p = 0.04) were the two most important predictors for the combined end point of death or listing as Status 1. CONCLUSIONS: Peak exercise SBP and percent predicted peak exercise VO2 are two inexpensive and easily measured noninvasive variables that can be used to further prognostically risk stratify ambulatory patients with CHF referred for heart transplantation with a peak exercise VO2 < or = 14 ml/min per kg.

Adult↗

Assessment of validity for EuroSCORE risk stratification system.

UNLABELLED: Prognostic scoring helps doctors, patients and their families to weigh the risks and benefits of medical care and clarifies their expectations. OBJECTIVE: We aimed to analyze the risk stratification performance of the EuroSCORE system because of its common use in Lithuania. DESIGN: EuroSCORE performance is assessed in terms of sensitivity, specificity, accuracy and area under the receiver operating characteristic (ROC) curve (AUC). Logistic regression is carried out for modeling categorical data and odds ratio calculations of being a non-survivor case for each EuroSCORE risk group. RESULTS: The study was completed on 1002 patients. Mean score for EuroSCORE was 4.77 +/- 2.8; ROC curve of 0.71; accuracy was 65.5%; 65.4% sensitivity and 67.2% specificity. CONCLUSIONS: EuroSCORE created a moderately predictive area under the ROC curve for our patient population. Probability of non-survival by logistic regression model for each EuroSCORE risk group is statistically significantly higher compared to the lower risk group. Predictions available from prognostic scoring systems could be useful in decision making when there is uncertainty in whether to carry out surgery or not.

Aged↗

Relapse risk assessment of transplantation for patients with chronic myeloid leukaemia.

OBJECTIVE: To analyse the risk factors of relapse before bone marrow transplantation (BMT) and to present the prognostic information as good as possible. METHODS: A total of 3142 patients, who underwent the allogeneic blood or bone marrow transplantation between 1989 and 1997 and were documented in the European Group for Blood and Marrow transplantation (EBMT), were included. Six possible risk factors including type of donor, stage of disease, age, gender, donor-recipient sex combination and the waiting time from diagnosis to transplantation of relapse were considered. The time to relapse was analysed by Kaplan-Meier curves and Cox regression with stratification on prognostic factors that did not satisfy the Proportional Hazard Assumption. RESULTS: An amount of 447 patients relapsed out of all 3142 patients. The relapse rate was 14.2%. Type of donor and stage of disease showed a clear prognostic effect, but failed the proportional hazard assumption. Therefore, the data were stratified on the combination of type of donor and stage of disease. Within these strata an additional significant effect of age could be observed. Relative risk of age > or = 40 vs age < 40 was 1.32 (95% confidence interval 1.09 - 1.59). The prognostic model is summarized graphically. CONCLUSIONS: The combination of type of donor, stage of disease and age of recipient at transplantation are important prognostic factors for relapse after BMT.

Adult↗

ST-segment depression in non-ST elevation acute coronary syndromes: quantitative analysis may not provide incremental prognostic value beyond comprehensive risk stratification.

BACKGROUND: It is unclear whether quantitative ST-segment assessment can improve risk stratification of unselected acute coronary syndrome (ACS) patients using the validated Global Registry of Acute Cardiac Events (GRACE) risk model. METHODS: In the prospective, multicenter, Canadian ACS Registry, the admission electrocardiogram was evaluated centrally at a blinded core laboratory. Patients with ST-elevation myocardial infarction and other electrocardiogram confounders were excluded. ST depression (ST down) was measured and summed in all leads except aVR. Patients with ST down were divided into 3 groups based on tertiles of cumulative ST down. A multivariable model was developed to examine the independent prognostic value of ST down severity after adjusting for other known prognosticators in the GRACE risk model. RESULTS: Among 2590 patients with non-ST-elevation ACS, more severe ST down was associated with advanced age, higher heart rate and Killip class, elevated creatinine, abnormal biomarkers, higher GRACE risk score, and higher 1-year mortality (all P < .001). After adjusting for these confounding prognosticators, the presence of any ST down remained independently associated with higher 1-year mortality (odds ratio 1.78, 95% CI 1.21-2.63, P = .004). However, the gradient of risk with increasing magnitude of ST down was no longer evident (adjusted odds ratios 1.77, 1.77, 1.81, for ascending tertiles of cumulative ST down, respectively). Moreover, quantitative ST down did not improve the model discrimination for 1-year mortality. The results were similar when the number of leads with ST down or the maximum magnitude of ST down was analyzed, after adjusting for tertiles of GRACE risk score or inhospital revascularization, or using the composite end point of death or myocardial (re)infarction at 1 year. CONCLUSIONS: Greater ST down is associated with other adverse prognosticators across the broad spectrum of non-ST-elevation ACS. Although the presence of any ST down is an independent predictor of 1-year mortality, its quantitative assessment is not as important as its mere presence when studied on the background of comprehensive clinical and biomarker evaluation in a nonclinical trial-based ACS population.

Aged↗

Soft tissue tumors of the abdominal wall: analysis of disease patterns and treatment.

HYPOTHESIS: Abdominal wall tumors, though clinically similar, have varying degrees of biological behavior. DESIGN: Retrospective review of prospective databases. SETTING: Memorial Sloan-Kettering Cancer Center. PATIENTS: Eighty-five patients with abdominal wall soft tissue tumors. MAIN OUTCOME MEASURES: Primary endpoints included time to first local recurrence, distant metastases, and disease-related mortality. Survival analysis was performed by Kaplan-Meier method, and comparisons were made by log-rank analysis. RESULTS: Thirty-nine desmoids, 32 soft tissue sarcomas (STS), and 14 dermatofibrosarcoma protuberans (DFSP) underwent surgery directed at achieving margin-negative resection. Unlike DFSP, most STS (77%) and desmoids(87%) were deep lesions requiring full-thickness abdominal wall resection and mesh reconstruction. Median follow-up time was 53 months, 101 months, and 31 months, with 5-year local recurrence-free survival rates of 97%, 100%, and 75%, for desmoids, DFSP, and STS, respectively. Desmoid tumors resected with positive microscopic margins had higher local failure rates (68% [positive margin] vs 100% [negative margin] 5-yr local recurrence-free survival, P<.05). For STS, high grade, deep location, and size at or above 5 cm were adverse prognostic factors for disease-specific and distant recurrence-free survival (P<.05); patients experiencing local recurrence was associated with decreased 5-year relapse-free survival rates (87% [primary] vs 50% [local recurrence], P<.05). Characteristically, no DFSP or desmoid developed distant metastases. Soft tissue sarcomas had significantly lower relapse-free survival rates than DFSP or desmoids (P<.05). CONCLUSION: Abdominal wall tumors demonstrate a broad spectrum of biological behavior. Desmoids and DFSP are a local problem. High grade, size at or above 5 cm, and deep location predict distant failure and tumor-related mortality for patients with STS. Complete surgical resection is the recommended treatment approach to achieve local control. Stratification by prognostic factors will facilitate selection of patients with STS for adjuvant systemic therapies.

Abdominal Muscles↗

Adjuvant therapy for pancreatic adenocarcinoma: what have we learned since 1985?

To review developments relevant to pancreatic adjuvant therapy since the publication of the Gastrointestinal Tumor Study Group (GITSG) trial of adjuvant therapy for pancreatic cancer in 1985. Our understanding of the pathology, surgical management, clinical and pathologic prognostic factors, potential importance of adjuvant therapy, and optimal design of adjuvant therapies have all undergone major evolution. Available data suggest: (1) the morbidity of pancreaticoduodenectomy has been reduced substantially, especially in major referral centers; (2) physicians, patients, and families recognize the importance of clinical trials and substantial numbers of patients are available for such trials; (3) factors such as tumor size, margin status, nodal involvement, histologic differentiation, and blood loss at surgery have an impact on postoperative outcomes; (4) the use of gemcitabine and patient-specific, anatomic planning for conformal radiotherapy has the potential to radically alter the adjuvant paradigm; (5) vaccine therapies have completed Phase I testing and are being incorporated into Phase II trials; and (6) careful application of relevant statistical principles is necessary to avoid the execution of ambiguous or uninterpretable trials. The need for effective adjuvant therapy is undisputed, because surgery alone is inadequate. Increasing numbers of patients are undergoing and recovering from surgery who are willing to consider clinical trials. Major cooperative group and single-institution efforts recently completed, ongoing, or currently planned using improved stratification for prognostic subsets, translational approaches based on molecular biology and/or genetic engineering, and newer chemoradiotherapeutic regimens are rapidly changing the landscape of this clinical arena into one of promise and possibility.

Adenocarcinoma↗

[Long-term outcome of acute massive pulmonary thromboembolism following thrombolysis].

OBJECTIVE: To evaluate in-hospital course and long-term outcome of acute massive pulmonary thromboembolism after thrombolysis and to determine its prognostic factors. METHODS: A total of 260 patients was retrospectively reviewed and followed up for 3.9 - 8.4 years. Close attention was paid to the clinical events, including death, recurrent thromboembolic events, chronic thromboembolic pulmonary hypertension, bleeding complications attributed to anticoagulant therapy, and requirement of oxygen therapy at home. Kaplan-Meier event-free survival curves were generated. RESULTS: The in hospital mortality rate was 8.5%, in which 68.2% were due to pulmonary thromboembolism itself, and the follow-up mortality rate was 31.7%, in which 29.2% were due to recurrent embolism. Univariate analysis showed that six variables were associated with the occurrence of clinical events: (1) Prior thromboembolic diseases; (2) Duration of anticoagulant therapy less than 6 months; (3) Inferior vena cava filter placement; (4) Remaining right ventricular dysfunction/dilatation after thrombolysis detected by echocardiography; (5) Systolic pulmonary pressure > 50 mm Hg after thrombolysis by echocardiography; (6) Greater than 30% residual obstruction of pulmonary vasculature identified by lung ventilation/perfusion scintigraphy before hospital discharge. Multivariate analysis identified three independent risk factors for long-term mortality of acute massive pulmonary thromboembolism after thrombolysis: (1) Systolic pulmonary artery pressure > 50 mm Hg (RR: 3.78, 95% CI = 2.70 - 4.86); (2) Right ventricular dysfunction/dilatation (RR: 2.18, 95% CI = 1.48 - 2.88); (3) Greater than 30% obstruction of pulmonary vasculature (RR: 1.99, 95% CI = 1.25 - 2.70). CONCLUSIONS: Doppler echocardiographic assessment after thrombolysis and ventilation/perfusion scintigraphy prior to hospital discharge are valuable to establish a new baseline condition, which is informative for risk stratification and prognostication of long-term outcome.

Aged↗

Curing childhood acute myeloid leukemia (AML) at the half-way point: promises to keep and miles to go before we sleep.

Childhood and adolescent acute myeloid leukemia (AML) is traditionally one of the hardest childhood cancers to successfully treat and had an overall survival well under 10% in the 1960s. Initial progress was made by three major events: (1) active chemotherapeutic agents were identified which led to remissions for the first time in this disease; (2) cooperative groups were instituted leading to important clinical trials; and (3) several single institutions began experimenting with the role of allogeneic matched sibling donor (MSD) BMT as effective intensification. Over the last 25 years, the cure rate has improved from <20% to 50% or higher. Most of the clinical research during this time of great advancement focused on two major themes: (1) the role of aggressive induction therapy in not only improving CR rates but in post-remission outcomes; and (2) the role of aggressive post-remission therapy in further improving survival, with an emphasis on high-dose Ara C-based chemotherapy, BMT, and supportive care. But we have "miles to go before we sleep." Some of the challenges that will lead to ongoing reduction of population-based mortality for AML through young adulthood include: (1) improving access of adolescents to pediatric AML therapy; (2) stratification by prognostic factors; (3) individualized therapy based on individual genetics and leukemia cell biology; (4) and the use of novel therapies including targeted immuno-conjugates and "small molecules" which disrupt abnormal signal transduction pathways. This brief review looks at both the advances over the last three decades as well as discusses the challenges moving forward for ultimately curing all children with this disease.

Acute Disease↗

Cardiac markers in the diagnosis of acute coronary syndromes.

Evolution of the role of cardiac markers has ranged from the diagnosis of acute myocardial infarction in patients with nondiagnostic electrocardiograms to prognostic risk stratification and to guide therapy. The technology to provide rapid, real time measurements by immunoassay has provided the laboratory and clinician with a range of test options. The principal changes have been the use of rapid serial marker measurements of well-recognized cardiac markers, and the development of immunoassays for the cardiac structural proteins. Measurement of cardiac troponins has generated a new diagnostic paradigm in patients with suspected acute coronary syndromes. There is now a new gold standard biochemical test for myocardial infarction. A range of interventions can be guided by troponin measurement. The use of troponin measurements is central to management of patients with suspected acute coronary syndromes. Future developments in this field will focus on the role of existing and novel markers of inflammation and ischemia.

Acute Disease↗

Molecular cardiovascular imaging.

Imaging with radionuclides has historically played an important role in detection of cardiovascular disease as well as in risk stratification and prognostication. With the growth of molecular biology have come new therapeutic interventions and the requirement for new diagnostic imaging approaches. Noninvasive targeted radiotracer-based strategies require the development of new instrumentation to meet these needs. This progress has been made possible with the availability of many technologic advances, which include dedicated micro single-photon emission computed tomography (SPECT) and micro positron emission tomography (PET) hybrid systems for small animal imaging. This review is a brief overview on the subject of molecular imaging. Basic concepts of molecular imaging are reviewed, followed by description of current technologic advances, and current applications to evaluate ischemic heart disease and potential therapeutic intervention. The emphasis is on the use of both SPECT and PET radiotracers, although other imaging modalities are also briefly discussed.

Angiogenesis Inducing Agents↗

A computer program for comparing survival experience of two groups after adjustment for relevant covariates.

A computer program is described which evaluates the difference in survival between two groups of patients based on the methods of Mantel [1] and Hankey and Myers [3]. Life table analysis is based on the stratification of prognostic variables. In addition, an adjusted survival curve is computed for one group of patients relative to the other group based on differences in the distribution of these variables. Plots of cumulative survival curves are optionally provided.

Computers↗

Clinical neurophysiologic monitoring and brain injury from cardiac arrest.

Electrophysiologic testing continues to play an important role in injury stratification and prognostication in patients who are comatose after cardiac arrest. As discussed previously, however, the adage about treating whole patients, not just the numbers, is relevant in this situation. EEG and SSEP can offer high specificity for discerning poor prognosis as long as they are applied to appropriate patient populations. As discussed previously, EEG and SSEP patterns change during the first hours to days after cardiac arrest and negative prognostic information should not be based solely on studies performed during the first 24 hours. Both electrophysiologic techniques also are susceptible to artifacts that may worsen the electrical patterns artificially and suggest a falsely poor prognosis. EEG is suppressed by anesthetic agents and hypothermia, both of which may produce ECS and burst suppression. Patients who experience respiratory arrest from a toxic ingestion of narcotics or barbiturates, in particular, may present with high-grade EEG patterns initially. Many patients also receive anesthetic medications at the time of tracheal intubation, which may linger beyond their normal half-life in patients who have hepatic or renal insufficiency or concurrent use of interacting medications. SSEP is much less susceptible to sedative anesthetic agents, but hypothermia is demonstrated to prolong evoked potential latencies. As therapeutic hypothermia becomes more common after cardiac arrest, the effect of temperature on electrophysiologic testing needs to be taken into account. The publications discussed previously also emphasize the need to adjust the prognostic value of electro-physiologic tests to the pretest probability of meaningful neurologic recovery in individual patients. Clearly, grade I EEG patterns and normal N20 potentials indicate a much better prognosis in patients who have a short du-ration of cardiac arrest, short duration of coma after resuscitation, and when the studies are performed within the first few days. In patients who remain in coma days after resuscitation and lack appropriate brainstem reflexes, however, even the most normal appearing electrophysiologic patterns do little to change the overall prognosis. Aside from prognostication, electrophysiologic testing holds great promise in defining the basic anatomy and physiology of coma emergence after cardiac arrest. In addition, quantitative EEG and automated evoked potentials have the potential to render these tools less subjective and arcane and more applicable for monitoring patients in the period during and immediately after resuscitation. Quantitative EEG also has great potential asa tool to define the time window for neuroprotective intervention and the means to track the response to such therapies in real time.

Brain↗

Perioperative cardiac evaluation for noncardiac surgery noninvasive cardiac testing.

Prognostic risk stratification to identify perioperative and long-term cardiac risk in selected patients undergoing noncardiac surgery is part of good clinical practice. Exercise variables associated with significant increased risk include poor functional capacity (eg, <4 metabolic equivalents), marked exercise-induced ST segment shift or angina at low workloads, and inability to increase or actually decrease systolic blood pressure with progressive exercise. Approximately 40% of patients tested before peripheral vascular surgery will have an abnormal exercise electrocardiogram (ECG). The predictive value for a perioperative event, ie, death or myocardial infarction, ranges from 5% to 25% for a positive test and 90% to 95% for a negative test. Whereas exercise cardiac imaging is the modality of choice in patients with a noninterpretable exercise ECG, pharmacological stress imaging should be used in the 30% to 50% of patients who require perioperative noninvasive risk stratification and are unable to perform an adequate level of exercise to test cardiac reserve. Myocardial perfusion variables predictive of increased cardiac events include severity of the perfusion defect, number of reversible defects, extent of fixed and reversible defects, increased lung uptake of thallium-201, and marked ST segment changes associated with angina during the test. The reported sensitivity and specificity of dobutamine-induced echocardiographic wall motion abnormalities in patients with peripheral vascular disease is similar to myocardial perfusion scintigraphy, but the confidence limits are wider due to the smaller sample size in these more recent studies. In conclusion, noninvasive cardiac testing should be used selectively in patients undergoing noncardiac surgery; the results provide useful estimates of short- and long-term risk of cardiac events, and the magnitude of abnormal response on noninvasive testing should be used to formulate decisions regarding the need for coronary angiography and subsequent revascularization.

Activities of Daily Living↗

Preoperative treatment strategies in stage III non-small cell lung cancer.

Recent experience has emphasized the need to include systemic chemotherapy in combined-modality management of locally advanced non-small cell lung cancer stage III. If definitive surgery is planned in these situations, preoperative application of drugs-induction chemotherapy-has many advantages in comparison to postoperative delivery. Patients' compliance to treatment, achievable dose intensities of drugs, possible locoregional downstaging, and frequent postoperative problems following complex resections are some of the arguments favouring preoperative chemotherapy. Despite numerous phase-II investigations, little evidence from randomized phase-III trials has been generated. Early inclusion of radiotherapy prior to definitive resection may help to improve preoperative downstaging. Besides available mature phase-II data, phase-III results from ongoing randomized trials are lacking to define the overall value of such a complex approach. Important issues in the future will aim at individualizing these intensive programs according to findings in clinical prognostic factor analyses and to prospectively validate a prognostic risk stratification. Data from translational and molecular research may further help to develop such evidence-based guidelines.

Carcinoma, Non-Small-Cell Lung↗

Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant.

PURPOSE: To investigate whether different procedure variables involved in the delivery of fractionated total body irradiation (TBI) impact on prognosis of patients affected by acute lymphoblastic leukemia (ALL) receiving allogeneic bone marrow transplant (BMT). METHODS AND MATERIALS: Ninety-three consecutive patients with ALL receiving a human leukocyte antigen (HLA) identical allogeneic BMT between 1 August 1983 and 30 September 1995 were conditioned with the same protocol consisting of cyclophosphamide and fractionated TBI. The planned total dose of TBI was 12 Gy (2 Gy, twice a day for 3 days). Along the 12-year period, variations in delivering TBI schedule occurred with regard to used radiation source, instantaneous dose rate, technical setting, and actual total dose received by the patient. We tested these different TBI variables as well as factors related to patient, state of disease, and transplant-induced disease to investigate their influence on transplant-related mortality, leukemia relapse, and survival. RESULTS: At median follow-up of 7 years (range 3-15 years) the probabilities of leukemia-free survival (LFS) and overall survival (OS) for the 93 patients were 60% and 41%, respectively. At univariate analysis, chronic graft versus host disease (cGvHd) (p = 0.0005), age (p = 0.01), and state of disease (p = 0.03) were factors affecting LFS whereas chronic GvHd (p = 0.0005), acute GvHd (p = 0.03), age (p = 0.0001), and GvHd prophylaxis (p = 0.01) were factors affecting overall survival. The occurrence of chronic GvHd was correlated with actually delivered TBI dose (p = 0.04). Combined stratification of prognostic factors showed that patients who received the planned total dose of TBI (12 Gy) and were affected by chronic GvHd had higher probabilities of LFS (p = 0.01) and OS (p = n.s.) than patients receiving less than 12 Gy and/or without occurrence of chronic GvHd. Moreover, TBI dose had a significant impact on LFS in patients transplanted in first remission (p = 0.05). At multivariate analysis, TBI dose was an independent factor affecting overall survival (p = 0.05) as well as chronic GvHd (p = 0.001) and age (p = 0.04). CONCLUSIONS: This retrospective analysis showed that different variables involved in TBI delivery may influence the occurrence of cGvHd and affect prognosis of patients with ALL receiving allogeneic BMT. The total dose of 12 Gy, administered in six fractions over 3 days, appears to be an effective and low toxic regimen for ALL patients transplanted in first remission.

Adolescent↗