2-year Point Research Articles

Changes in Radiographic and Clinical Outcomes With Primary Treatment Adult Spinal Deformity Surgeries From Two Years to Three- to Five-Years Follow-up

Retrospective analysis of data entered prospectively into a multicenter database-clinical and radiographic outcomes assessment. Our hypothesis is that between the 2-year and the 3- to 5-year points surgically treated adult spinal deformity patients will show significant reduction in outcomes by Scoliosis Research Society (SRS), Oswestry Disability Index (ODI), and numerical rating scale back and leg pain scores and will show increasing thoracic kyphosis, loss of lumbar lordosis, and loss of coronal and sagittal balance. Most analyses of primary presentation adult spinal deformity surgery assess 2-year follow-up. However, it is established that in some patients unfavorable events occur between the 2-year and 5-year points. The cohort of 113 patients entered into a multicenter database with complete preoperative, 2-year, and 3- to 5-year data. All patients who had adult spinal deformity and surgical treatment represented their first reconstruction. Diagnoses were scoliosis (82.5%), kyphosis (10%), and scoliosis and kyphosis combined (7.5%). Outcome measures and basic radiographic parameters (curve size, thoracic and lumbar sagittal plane, coronal and sagittal balance) were assessed at those 3 time intervals. Complications (pseudarthrosis/implant failure, infection, and junctional deformities) were assessed at the 2-year and the 3- to 5-year (mean, 3.76 years) points. RESULTS.: The mean major curve Cobb angle (preoperative, 57°; 2-year, 29°; 3-5 year, 26°); thoracic kyphosis T5 to T12 (30°, 31°, 32°) and lumbar lordosis T12 to sacrum (48°, 49°, 51°) did not change from the 2-year to ultimate follow-up. Likewise, coronal and sagittal balance parameters were the same at 2-year and ultimate follow-up. SRS total scores and modified ODI were similar at the 2 year and final follow-up (SRS: 3.89-3.88; ODI: 19-18). Preoperative SRS total score was 3.17. Six patients demonstrated complications at the 2-year point and additional 9 patients demonstrated complications at the 3- to 5-year point. Those 9 patients with complications at ultimate follow-up demonstrated significant deterioration in their ODI and SRS scores when compared with the patients who did not have complications at ultimate follow-up. Contrary to our hypothesis, we could not establish deterioration in mean radiographic or clinical outcomes between the 2-year and 3- to 5-year follow-up points when analyzing the group as a whole. However, for the 9 patients who experienced complications between 3- and 5-year follow-up, their outcomes were significantly worse than for the other 104 patients.One should not anticipate an overall radiographic and clinical deterioration of the outcomes of surgically treated primary presentation adult spinal deformity patients in this studied time interval. However, close to 10% of patients will experience a new complication at the 3- to 5-year point, most commonly implant failure/nonunion and/or junctional kyphosis, which will negatively effect the patient-reported outcome.

Issues of loss to follow-up in a population study of traumatic brain injury (TBI) followed to 3 years post-trauma

Primary objective: To examine loss to follow-up (LTFU) using a population with traumatic brain injury (TBI) to include a range of severity and to follow participants to 3 years post-injury. Also investigated were cause of TBI and employment status.Research design: The research included 947 adults from a TBI population study. Data were obtained on severity, cause of TBI and employment status and participants were followed up at 1, 3, 6, 12, 24 and 36 months after injury. Chi-squared analyses were used to examine rates of loss to follow-up.Main outcome and results: Overall LTFU increased from 22% at 1 month post-injury to 81% at 3-year follow-up. Most participants (52%) were employed at the time of their TBI, with 39% of TBIs being motor vehicle related. Lower LTFU at 2 and 3 years post-TBI was significantly associated with severe TBI. Within the mTBI sub-group significantly higher LTFU at 1 and 6 months after injury and at 2 and 3 years post-injury was associated with TBI from assault. Those sustaining mTBI from a fall or sport-related injury showed significantly lower LTFU at the 6-month, 12-month and 2-year follow-up points. The highest LTFU was noted for unemployed participants, with retired participants showing the lowest rate.

Contemporary Post Surgical Management of Differentiated Thyroid Carcinoma

Risk assessment is the cornerstone of contemporary management of thyroid cancer. Following thyroid surgery, an initial risk assessment of recurrence and disease-specific mortality is made using important intra-operative findings, histologic characteristics of the tumor, molecular profile of the tumor, post-operative serum thyroglobulin and any available cross-sectional imaging studies. This initial risk assessment is used to guide recommendations regarding the need for remnant ablation, external beam irradiation, systemic therapy, degree of TSH suppression, and follow-up disease detection strategy over the first 2 years after initial therapy.While this initial risk stratification provides valuable information, it is a static representation of the patient in the first few weeks post-operatively that does not change over time. Depending on how the patient responds to our initial therapies, the risk of recurrence and death may change significantly during follow-up. In order to account for differences in response to therapy in individual patients and to incorporate the impact of treatment on our initial risk estimates, we recommend a re-stratification of risk at the 2-year point of follow-up. This re-stratification provides an updated risk estimate that can be used to guide ongoing management recommendations including the frequency and intensity of follow-up, degree of ongoing TSH suppression, and need for additional therapies.Ongoing management recommendations must be tailored to realistic, evolving risk estimates that are actively updated during follow-up. By individualizing therapy on the basis of initial and ongoing risk assessments, we can maximize the beneficial effects of aggressive therapy in patients with thyroid cancer who are likely to benefit from it, while minimizing potential complications and side effects in low-risk patients destined to have a full healthy and productive life after minimal therapeutic intervention.

HIV Status Does Not Affect the Outcome of Autologous Stem Cell Transplantation (ASCT) for Non-Hodgkin Lymphoma (NHL)

Randomized trials comparing autologous stem cell transplant (ASCT) to conventional chemotherapy have demonstrated superior survival among HIV-negative ASCT patients with relapsed non-Hodgkin lymphoma (NHL). Recent trials explored the feasibility of ASCT in the HIV setting. Although these studies have shown that ASCT in HIV-positive NHL patients (HIVpos-NHL) is well tolerated, the impact of HIV infection on long-term transplant outcome is not well characterized. Ongoing comparison of long-term survival following ASCT in HIVpos-NHL patients and HIVneg-NHL patients will allow investigators to explore whether there should be inclusion of HIVpos-NHL patients in ASCT trials. To study long-term outcome we conducted a single-institution matched case-controlled study in HIVpos-NHL patients (cases) and HIVneg-NHL patients (controls). Twenty-nine patients with HIVpos-NHL were matched with HIVneg-NHL controls on sex, time to ASCT, year of transplant, histology, age, disease status, number prior regimens, and conditioning regimen. Nonrelapse mortality (NRM) was similar: 11% (95% confidence interval [CI]: 4%-28%) in HIVpos-NHL patients and 4% (95% CI: 1%-25%) in HIVneg-NHL controls (P = .18). Two-year disease-free survival (DFS) for the HIVpos-NHL patients was 76% (95% CI: 62%-85%) and 56% (95% CI: 45%-66%) for the HIVneg-NHL controls (P = .33). Overall survival was also similar; the 2-year point estimates were 75% (95% CI: 61%-85%) and 75% (95% CI: 60%-85%), respectively (P = .93), despite inclusion of more poor risk HIVpos-NHL patients. These results provide further evidence that HIV status does not affect the long-term outcome of ASCT for NHL, and therefore HIV status alone should no longer exclude these patients from transplant clinical trials.

Invited Commentary

Invited Commentary

Clinical and non-clinical factors influencing postoperative health-related quality of life in patients with colorectal cancer

The aim was prospectively to evaluate health-related quality of life (HRQoL) after treatment of potentially curable colorectal cancer. HRQoL measurements were acquired by postal questionnaire sent to 210 patients with colorectal cancer for whom there was at least of 1 year of follow-up. Data were collected at seven time points using two validated questionnaires, QLQ-C30/CR38 and Short Form 12. Scores from salient HRQoL domains were compared with population norms. The independent associations between HRQoL and 13 treatment and non-treatment variables were evaluated using linear regression. Recurrences were excluded. A total of 186 patients (88.6 per cent) were followed up for 1 year, with 136 (64.8 per cent) and 84 (40.0 per cent) reaching the 18-month and 2-year follow-up points respectively. HRQoL improved rapidly after surgery, with most scores equating to population norms by 3-6 months. In addition to baseline performance status, three factors were associated with significantly poorer HRQoL scores: age less than 65 years, low rectal anastomoses and presence of a stoma. The areas predominantly affected were normal daily routines, work and social activities. HRQoL largely recovered by 6 months in disease-free patients, but some subgroups had poorer scores than others.

Pediatric Brain Tumor Patients: Their Parents’ Perceptions of the Hospital Experience

Studies have shown that admission to the hospital of a child can induce feelings of fear and helplessness in parents, challenging usual patterns of coping and parenting competence. Stress has been associated with parents' need to establish effective communication with staff and their need for information, ready access to their children, and participation in decision making relating to their child's care. This study of coping and adjustment was undertaken with the parents, including mothers and fathers, of children under 18 years of age diagnosed with a brain tumor, presenting at Royal Children's Hospital, Melbourne, between 2001 and 2002 (N=53). It was a prospective study using repeated measures over time. Participants in the study were involved in a questionnaire interview at 4 different points: at the time of diagnosis, 6 months postdiagnosis, 1 year postdiagnosis, and 2 years postdiagnosis, in which they were asked, among other things, about their experience of the hospital. The point of diagnosis was marked by a high level of dependence, with parents coping with rapid decision making and shock, and the surrender of care of their child. Parents identified high levels of information need but noted that they were often too stressed to take in information early on, and that this information need persisted up to the 2-year postdiagnosis point. More parents expressed dissatisfaction with the hospital and particularly with their interactions with the health care team at the 6-month post-diagnosis period, reflecting a possible reduction in attention given to families once they had settled into the treatment routine and the crisis of diagnosis had passed.

Improving Survival and Reducing Toxicity with Chemotherapy in Advanced Non-Small Cell Lung Cancer

The role of chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) has been debated over three decades, but it is only relatively recently that chemotherapy has become a standard of care for this disease. In addition to prolonging survival, chemotherapy can palliate distressing symptoms. Concerns that the adverse effects of chemotherapy are likely to outweigh its benefits have largely not been confirmed by quality-of-life data reported among patients with good performance status. Platinum-based chemotherapy regimens in which cisplatin or carboplatin are partnered by a third-generation cytotoxic drug such as gemcitabine, paclitaxel or vinorelbine, have similar activity and efficacy, but differ in adverse effect profiles. Response rates of 30-40% should be expected with median and 1-year survival of 8-10 months and 30-40%, respectively. In the second-line setting chemotherapy with docetaxel has been shown to be significantly superior to best supportive care alone. In a recent trial that compared docetaxel to the novel antifolate, pemetrexed the response rates and survival rates did not differ, but the toxicity profile favored pemetrexed. Overall, these data demonstrate that progress has been made in the use of chemotherapy to improve survival in patients with NSCLC without increasing the incidence of further toxicity. In the past, the potential to survive 1 year was extremely small, whereas now many more patients reach this milestone as well as the 2-year point. However, a plateau has probably been reached with existing cytotoxic drugs and there is a general belief that the next significant advance in the treatment of NSCLC will come from the addition of drugs that target specific molecular pathways in sequence with standard chemotherapy regimens.

Predicting mortality in patients with rheumatoid arthritis.

A number of different variables have been proposed as risk factors for mortality in patients with rheumatoid arthritis (RA), but limited prospective information on the magnitude of their effects is available. This study was undertaken to evaluate the relative predictive strength and usefulness of a wide range of variables on the risk of mortality in a large, long-term, prospectively studied cohort of patients with RA. Over a 20-year period of followup beginning in 1981, 1387 consecutive RA patients were seen in a single clinic. A wide range of clinical and demographic assessments were recorded and entered into a computer database at the time of each clinical assessment. Assessment of predictive strength included determination of standardized and fourth-versus-first-quartile odds ratios (ORs), goodness-of-fit measures, and contributing fraction. The Health Assessment Questionnaire (HAQ) disability index was the strongest clinical predictor of mortality. A 1-SD change in the HAQ resulted in a much larger increase in the odds ratio for mortality compared with a 1-SD change in global disease severity, the next most powerful predictor of mortality (OR 2.31 versus 1.83). Considering the contributing fraction, mortality would be reduced by 50% for the HAQ and by 33% for global disease severity if patients in the fourth quartile for these variables could be switched to the first quartile. Global disease severity, pain, depression, anxiety, and laboratory and radiographic features were significantly weaker predictors. Disease duration, nodules, and tender joint count were clinical variables that provided very little predictive information. In multivariable analyses, HAQ and other patient self-report measures were significantly better predictors than were radiographic and laboratory variables. A single baseline observation provided the least information, with substantially increasing predictive ability associated with 1-year, 2-year, and all-time point followup observations (time-varying covariates). In this large 20-year study from routine clinical practice, the HAQ was the most powerful predictor of mortality, followed by other patient self-report variables. Laboratory, radiographic, and physical examination data were substantially weaker in predicting mortality. We recommend that clinicians collect patient self-report data, since they produce more useful clinical outcome information than other available clinical measures.

Intradiscal Electrothermal Treatment for Chronic Discogenic Low Back Pain

Prospective longitudinal study with a minimum 2-year follow-up. To assess the long-term outcome of a group of patients with chronic discogenic low back pain who had failed to improve with comprehensive nonoperative care and who were subsequently treated with intradiscal electrothermal therapy (IDET). Previous reports of patient outcomes at 1 year after IDET have demonstrated statistically significant improvement. The study group comprised 58 patients with chronic symptoms of more than 6 months who failed to improve with nonoperative care and subsequently underwent IDET. VAS pain scores, SF-36 scores, and sitting tolerance times were collected pretreatment and at 6, 12, and 24 months. Mean duration of pre-IDET symptoms was 60.7 months. The minimum follow-up at data collection was 24 months. The study group (n = 58) demonstrated a significant improvement in pain as demonstrated by statistically significant improvement in VAS scores and bodily pain SF-36 scores. The IDET-treated group demonstrated a significant improvement in physical function as noted by statistically significant improvement in sitting tolerance times and physical function SF-36 scores. Bodily pain and physical function scores demonstrated significant improvement between the 1- and 2-year observation points. Additionally, quality of life improvement was demonstrated by a statistically significant improvement in all the SF-36 subscales. A cohort of patients with chronic discogenic low back pain who had failed to improve with comprehensive nonoperative care demonstrated a statistically significant improvement in pain, physical function, and quality of life at 2 years after IDET.

Treatment effects of cognitive processing therapy on cognitive distortions of female child sexual abuse survivors

Fifty-three female adults with a history of child sexual abuse (CSA) were assessed to determine whether Cognitive Processing Therapy for Sexual Abuse (CPT-SA) affects cognitive distortions. CPT-SA is a 17-week manualized treatment designed to alleviate cognitive distortions as well as symptoms of PTSD and depression. At the initial assessment, 28 subjects were assigned to treatment, while 25 subjects entered a minimal-attention condition. Participants were assessed at pretreatment, posttreatment, 3-month follow-up, and 1-year follow-up. The authors examined the correlation between PTSD severity, subscales of the Personal Beliefs and Reactions Scale (PBRS), and higher-order scales of the World Assumptions Scale (WAS). Most PBRS subscales were significantly correlated with PTSD severity at all assessment periods. Paired samples t tests indicated significant differences between pretreatment and posttreatment severity of distortions on both the PBRS and WAS for participants completing treatment. No significant differences in distortions were found between postassessment, 3-month follow-up, and 1-year follow-up points.

The westmead pediatric TBI multidisciplinary outcome study: Use of functional outcomes data to determine resource prioritization

Objective: To measure functional outcome in the 2 years after traumatic brain injury (TBI) in 2 groups of children and to determine the usefulness of a TBI severity classification system for resource allocation.Design: Prospective inception cohort study with 3 assessment points during the 2 years after trauma.Setting: Tertiary pediatric trauma center in Sydney, Australia.Participants: Eighty-one consecutive admissions aged 0 to 14 years. Fifty-one were allocated to the Mild (n = 26) or Severe (n = 25) TBI groups, according to preset determinants of severity; 30 admissions with non-TBI trauma constituted the control group.Main Outcome Measures: Standardized psychometric and clinical assessments of cognition, communication and feeding ability, motor performance (ambulation, fine and gross motor), neurologic status, self-care independence, and school/academic performance.Results: Those with Mild TBI severity had no significant deficits at the 2-year data point. In contrast, those in the Severe TBI group demonstrated continued problems with fine motor performance, neurologic status, self care, and school/academic performance.Conclusions: A classification system has been developed that may be useful in the allocation of children with a TBI, age younger than 15 years, to 1 of 2 severity groups early in their rehabilitation. This classification system may be useful in determining areas of high and low resource prioritization.

Predictors of Physical Aggression in Children With Attention-Deficit/Hyperactivity Disorder

The present investigation examined factors that predict physical aggression in children with attention-deficit/hyperactivity disorder (ADHD). Stepwise, multiple regression-analyses were used to examine predictors of children's physical aggression as rated by parents at a 1-year follow-up point and by teachers at both 1- and 2-year follow-up points. Early parent and teacher ratings of verbal aggression (ie, cursing, teasing, and threatening) accounted for the greatest proportion of the variance in physical aggression ratings obtained at follow-up. None of the other predictor variables, including early ratings of physical aggression and ADHD behaviors, contributed significant additional variance beyond that accounted for by early verbal aggression ratings. Temporal and cross-informant analyses revealed that the relationship between verbal aggression and later physical aggression was situation-specific for teacher ratings but not parent ratings. Although physical aggression may emerge early in development, these data suggest that verbal aggression represents a stable, temperamental characteristic that may be of greater value than early physical aggression for predicting later physically aggressive acts.

Thyroplasty type I: Short- versus long-term results

Objective: After thyroplasty type I, significant improvement has been reported in objective measures of vocal function. The purpose of this investigation was to compare the short- and long-term results in patients undergoing thyroplasty type I. Methods: Data on 26 patients who had undergone thyroplasty type I for management of unilateral vocal fold paralysis were compared from before surgery to the short-term (1-month) and long-term (>1-year) postoperative assessment points. Statistical analysis included paired tests to assess the significance of between-group differences. Results: Significant differences were found between the preoperative and both postoperative evaluations for the measures of mean glottal flow rate, maximum phonation time, jitter, shimmer, and harmonic-to-noise ratio. However, no significant differences were found between the 1-month and >1-year assessment points. Conclusions: The results for the parameters studied appeared to reach maximum improvement within 1 month after surgery. It is possible that the effects of time, including the normal aging process, hormonal changes, or other alterations in general health, may require longer follow-up to better address these issues. (Otolaryngol Head Neck Surg 2000;122:533-6.)

Intracranial aneurysms treated with the Guglielmi detachable coil: midterm clinical results in a consecutive series of 100 patients.

A prospective study was designed to evaluate clinical outcome in a series of 100 consecutively treated patients who underwent endovascular embolization of 104 intracranial aneurysms using Guglielmi detachable coils (GDCs). Midterm clinical outcome (2-6 years, average 3.5 years) was obtained for 94 patients and was classified according to a modified Glasgow Outcome Scale. Of nine patients treated in the acute phase of severe subarachnoid hemorrhage (Grade IV or V), seven died from the initial hemorrhage, one had a poor outcome, and one had a fair midterm outcome, with no post-GDC embolization hemorrhages. Twenty patients underwent subsequent surgical or endovascular procedures that did not include the use of GDCs. These included aneurysm clipping in nine patients and parent vessel sacrifice in 11 patients. None of these 20 patients experienced post-GDC embolization hemorrhage. The postoperative midterm clinical outcomes of these 20 patients did not significantly differ from the outcomes of patients who underwent GDC embolization as their definitive treatment. Six patients died of unrelated causes prior to reaching the 2-year survival point, with no post-GDC embolization hemorrhage. The midterm outcomes of the remaining 61 patients who underwent GDC embolization as their definitive treatment were classified as excellent (46 patients [75%]), good (seven patients [11%]), fair (three patients [5%]), poor (one patient [2%]), or dead (four patients [7%]). All four patients died from giant lesions. At midterm follow up, the surviving 57 patients' neurological statuses were unchanged or improved in 54 cases and worsened in three cases. The midterm post-GDC embolization hemorrhage rate was 0% for small aneurysms, 4% (one case) for large aneurysms, and 33% (five cases) for giant lesions. The GDC procedure is a safe, effective, and reliable means of preventing aneurysm hemorrhage in patients with small and large intracranial aneurysms. Results, however, are less satisfactory in cases involving giant lesions. Further follow-up review is necessary to establish durability in the longer term. Patients with Grade IV or V subarachnoid hemorrhage in this series generally had poor outcomes even if the GDC procedure was successful in occluding the aneurysm.

Durability of remission after ABMT for NHL: the importance of the 2-year evaluation point

Few series describing the results of autologous bone marrow transplantation (ABMT) for the treatment of non-Hodgkin's lymphoma report mature follow-up. We retrospectively reviewed 110 adults with NHL treated with ABMT from 1988 to 1993. Overall survival and relapse-free survival were 50% and 35%, respectively. Estimated median relapse-free survival was 16 months. There was no statistically significant difference in relapse-free or overall survival by low, intermediate, and high-grade histologies, as defined by the International Working Formulation. The most powerful negative prognostic variable was an elevated LDH at the time of transplant (relapse-free survival 17% vs 42% for those with a normal LDH). Forty-seven patients were in complete remission 2 years after transplant. Extended follow-up revealed that 100% of patients with high-grade histologies remained in complete remission, whereas patients with intermediate-grade and low-grade histologies remained at risk of relapse with longer follow-up. Of 22 patients with diffuse large cell lymphoma (LCL) or immunoblastic (IBL) histologies, eight of eight with IBL remain in continued remission, while four of 14 with LCL relapsed 24-48 months after ABMT. We conclude that patients with high-grade histologic subtypes of NHL who are in complete remission 2 years after ABMT are likely to be cured. However, patients with intermediate and low-grade histologic subtypes are at continued risk of relapse and require appropriate clinical surveillance for at least 48 months after ABMT.

Serial pulmonary function studies in children treated for newly diagnosed Hodgkin's disease with mantle radiotherapy plus cycles of cyclophosphamide, vincristine, and procarbazine alternating with cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine.

The pulmonary toxicity of bleomycin-containing chemotherapy combined with mantle radiotherapy in children treated for Hodgkin's disease was longitudinally assessed. The results of serial pulmonary function studies in 37 children, newly diagnosed and treated at St. Jude Children's Research Hospital between September 23, 1983, and June 30, 1988, with cyclophosphamide, vincristine, and procarbazine (COP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus low dose mantle radiotherapy are analyzed. All patients had pulmonary function studies at least before the first bleomycin dose, after completion of radiotherapy, and serially upon discontinuation of therapy. Bleomycin therapy was withheld whenever measured carbon monoxide diffusing capacity was less than 50% of the predicted value. Vital capacity, diffusing capacity, and diffusing capacity per unit of alveolar volume declined during the first 6 months of therapy but improved there after. At 2 years postdiagnosis, diffusing capacity per unit of alveolar volume remained significantly reduced. Only one patient was symptomatic at the 2-year point. The survival rate of these patients was 95% at a median follow up of 93 months. If bleomycin is with held when diffusing capacity is diminished to 50% predicted, clinical compromise of pulmonary function appears to be minimal in pediatric patients receiving alternating cycles of COP/ ABVD in combination with low-dose mantle radiotherapy. Survival was excellent, even with reduction of the total bleomycin dose.

Course of major depression in non-referred adolescents: a retrospective study

This article reports on a naturalistic study of the course of illness of 38 children diagnosed as having a current or past episode of major depression out of a sample of 275 children who were selected by a method not related to their psychopathology or treatment-seeking behavior. Assessments of the presence of depression and the course of this disorder were made using structured clinical interviews (DICA and DICA-P) and a criterion-based diagnostic system (DSM-III). Longitudinal methods of data analysis included the use of life tables. The proportion of children depressed for 2 years closely resembles the results found in investigations of children who sought treatment for a psychiatric disorder. The probability of remaining depressed in these children was 21% at 1 year after onset, and10% at the 2-year point. This parallels the rate of chronicity and the decline in rates of recovery which occur over time in adult depression.

Prognostic Significance of Additional Cytogenetic Abnormalities at Diagnosis of Philadelphia Chromosome-positive Chronic Granulocytic Leukemia

Abstract Of 661 patients with Philadelphia chromosome (Ph)-positive, nonblastic chronic granulocytic leukemia, 58 had cytogenetic abnormalities in addition to the Ph at the time of diagnosis. Twenty patients had reduplication of the Ph in one or more metaphases. Twenty-one patients with a single Ph exhibited hyperdiploidy in one or more metaphases. Eleven patients had two or more hypodiploid metaphases as their only numerical abnormality. The remaining six patients had a variety of abnormalities. Many patients had more than one type of abnormality. Survival of patients in the different subgroups was similar, but these 58 patients had a shorter course than the 603 patients without additional cytogenetic abnormalities (P less than .02). Survival curves for the two populations did not diverge until the 2-year point, after which the annual death rate among patients with additional cytogenetic abnormalities was approximately 40% higher than that of patients without such abnormalities. The two populations had similar relative risk values according to a hazard ratio formula previously described by the International CGL Prognosis Study Group. Thus, they would have been expected to have essentially identical survival curves. We conclude that the presence of additional cytogenetic abnormalities at the time of diagnosis constitutes an independently significant prognostic feature with an unusually delayed influence on survival.

Prognostic significance of additional cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia

Of 661 patients with Philadelphia chromosome (Ph)-positive, nonblastic chronic granulocytic leukemia, 58 had cytogenetic abnormalities in addition to the Ph at the time of diagnosis. Twenty patients had reduplication of the Ph in one or more metaphases. Twenty-one patients with a single Ph exhibited hyperdiploidy in one or more metaphases. Eleven patients had two or more hypodiploid metaphases as their only numerical abnormality. The remaining six patients had a variety of abnormalities. Many patients had more than one type of abnormality. Survival of patients in the different subgroups was similar, but these 58 patients had a shorter course than the 603 patients without additional cytogenetic abnormalities (P less than .02). Survival curves for the two populations did not diverge until the 2-year point, after which the annual death rate among patients with additional cytogenetic abnormalities was approximately 40% higher than that of patients without such abnormalities. The two populations had similar relative risk values according to a hazard ratio formula previously described by the International CGL Prognosis Study Group. Thus, they would have been expected to have essentially identical survival curves. We conclude that the presence of additional cytogenetic abnormalities at the time of diagnosis constitutes an independently significant prognostic feature with an unusually delayed influence on survival.