|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 1999 American Society for Clinical Oncology Quality-Adjusted Survival After Treatment for Acute Myeloid Leukemia in Childhood: A Q-TWiST Analysis of the Pediatric Oncology Group Study 8821From the Children's Hospital and Dana-Farber Cancer Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Dartmouth Medical School, Lebanon, NH; Children's Hospital of Michigan, Barbara Ann Karmanos Cancer Institute and Wayne State University, Detroit, MI; Texas Children Cancer Center and Baylor College of Medicine, Houston, TX; Emory University School of Medicine, Atlanta, GA; and Pediatric Oncology Group Statistical Office, Department of Statistics, Gainsville, FL. Address reprint requests to Susan K. Parsons, MD, Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; email parsons{at}a1.tch.harvard.edu
PURPOSE: To describe quality-of-life considerations in postremission therapies for children with acute myelogenous leukemia. PATIENTS AND METHODS: A quality-adjusted survival analysis, using the quality-adjusted time without symptoms or toxicity (Q-TWiST) method, was applied to Pediatric Oncology Group Trial 8821, which compared randomized assignment with intensive consolidation chemotherapy (CC) or autologous bone marrow transplantation (ABMT). Nonrandomized assignment to allogeneic bone marrow transplantation (allo BMT) on the basis of availability of a matched related donor was also evaluated. A 25-patient cohort provided data for modeling chronic graft-versus-host disease. The Q-TWiST analysis was performed based on the intent-to-treat principle. RESULTS: As previously reported, the 3-year event-free survival was not significantly different between the randomized arms (CC v ABMT). At a median follow-up of 5 years (of the censoring distribution), the CC group had less time in toxicity (TOX) and more time without symptoms or toxicity (TWiST), relapse-free time, and alive time than patients assigned to ABMT (none of these were statistically significant). Compared with the CC group, allo BMT patients spent more time in TOX (P < .001), more time in TWiST (P = .06), and had more relapse-free time (P = .03) and time alive (P = .07). Allo BMT was superior to ABMT with greater time in TWiST (P = .02), relapse-free time (P = .01), and time alive P = .002). CONCLUSION: The Q-TWiST analysis is a powerful decision aid in choosing among alternative therapies. Prospective information on patient preferences will facilitate future trials evaluating treatment outcomes. Refinements in the Q-TWiST method could be included to further enhance the power of this patient care decision-making tool.
ADVANCES IN CHEMOTHERAPY have significantly improved survival in childhood acute myeloid leukemia (AML). In particular, intensification of induction therapy and improvements in supportive care have had a dramatic impact on outcome.1,2 An estimated 75 to 85% of all pediatric patients with AML successfully achieve a remission after induction therapy.1,3-6 After induction remission, allogeneic bone marrow transplantation (allo BMT) has been recommended for most patients with histocompatible related donors.7-14 It has been estimated, however, that less than 20% of children have access to a matched related donor. Given the limited availability of allo BMT to most children with AML, alternative treatments, including intensified consolidation chemotherapy (CC) and autologous bone marrow transplantation (ABMT), have been pursued with encouraging results.5,15-24 In May 1996, the Pediatric Oncology Group (POG) reported the results of a randomized, controlled trial (POG 8821) of ABMT versus intensive CC for children with AML in first clinical remission.25 This intent-to-treat analysis found no significant difference in disease-free survival between the two modalities at a median follow-up of 3 years. Allo BMT, offered to patients after documented complete remission and identification of a suitably matched family donor, was marginally better than chemotherapy in both overall and disease-free survival. This study addressed the potential important differences in the quantity of survival among the treatment alternatives for childhood AML, but it was not designed to provide insight into the quality of that survival. Recently, the critical importance of secondary end points, such as ability to tolerate treatment and the impact of treatment on functional status and overall quality of life (QOL), has been recognized, particularly when alternative treatment options with similar potential for long-term survival become available. The methodologic challenges posed by the assessment of these secondary end points are substantial. To evaluate adequately these end points, new techniques are needed to assess both the quantity and the quality of survival. Ideally, QOL information is best collected prospectively in the course of the clinical trial directly from patients. Given the relatively recent recognition of QOL as an important study end point, however, many clinical trials, such as the POG 8821 study, lack prospective information on QOL. Techniques have been developed for retrospective analysis of the tradeoffs of risks and benefits of alternative treatments in clinical trial. The quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) method combines end points such as toxicity, relapse, and death to describe the typical or average experience for patients on a particular treatment or trial. The Q-TWiST technique was originally developed to evaluate adjuvant therapies for resectable breast cancer and has also been applied to clinical trials in patients with rectal cancer, human immunodeficiency virus, and malignant melanoma.26-29 To characterize better the quality-adjusted survival of children with newly diagnosed AML, weighing the impact of treatment-related toxicity versus potentially improved survival, we performed a Q-TWiST analysis on the results of POG 8821. We found enhanced quality-adjusted survival for allo BMT compared with ABMT or CC and superior results for the CC subset over the ABMT group.
Patient Selection and Treatment The design and main results of the POG Study 8821 are reported elsewhere.25 The randomized controlled study was designed to compare CC with ABMT for childhood AML in first clinical remission. The study also evaluated the results of allo BMT after induction of remission for the subset of patients with an identified (matched family) donor, as previously reported.30 The remaining patients without a matched donor were randomized to receive either continued, intensive, multiagent chemotherapy or ABMT. The original POG trial was analyzed using the intent-to-treat method in which patient outcomes were compared by the treatment assignment rather than the treatment received. The Q-TWiST analysis followed this designation to allow for direct comparisons with the previous report. Figure 1 summarizes the treatment assignments of the study population and the distribution of treatments actually received. Of the 115 patients assigned to the ABMT arm of the study, 71 (61.7%) actually received ABMT, 21 patients relapsed before their marrow could be obtained, 14 received chemotherapy due to parental preference, five received allo BMT, three were deemed unsuitable candidates due to disseminated fungal sepsis, and one was lost to follow-up. The disproportionate number of patients assigned to the ABMT arm who did not receive the designated treatment mirrors the trend reported in several previous studies.15,16,31,32 This is in marked contrast to the CC arm of the study in which 113 (96.6%) of the 117 patients received the assigned treatment. Among the allo BMT group, 68 (76.4%) of 89 patients assigned to allo BMT actually received the treatment. The principal reason for not receiving allo BMT was relapse (16 patients, or 18.0%). A total of 75 patients received allo BMT, including the 68 patients assigned to allo BMT and an additional seven patients who were initially randomized to CC (two patients) or ABMT (five patients).
Reporting of Toxicity
Q-TWiST For those patients receiving an allo BMT, a fourth health state was also defined for the period during which patients experienced symptoms of severe chronic graft-versus-host disease (CGVHD), based on established criteria.33 Detailed information for the duration of CGVHD was not available for the entire data set and was therefore estimated from the 25 patients treated at the Dana-Farber Cancer Institute (DFCI) who received allo BMT for first-remission AML during the time period of the POG study. The estimated duration of the health state CGVHD was based on the actual dates of onset of CGVHD in the DFCI subset and, where appropriate, the dates of complete resolution of active CGVHD. The Q-TWiST method weights the mean duration of the clinical health states by utility coefficients, uTOX, uREL, and uCGVHD, to reflect the average value (relative to TWiST) of time in the health states TOX, REL, and CGVHD, respectively. These utility coefficients are measured on a scale from 0 to 1, where 0 represents QOL as bad as death and 1 represents QOL as good as TWiST. The Q-TWiST was calculated as:
where TOX, TWiST, REL, and CGVHD represent the clinical health state duration, measured in months. The final term in brackets applies only to the set of patients receiving allo BMT with the addition of the quality-adjusted time in CGVHD.
To calculate estimates of the mean duration of each health state, Kaplan-Meier survival curves of overall survival (OS), relapse-free survival (RFS), and time to the end of toxicity were determined for each treatment group. The RFS and end-of-toxicity curves were used to partition the OS time within the median follow-up interval of the cohort (5 years). TOX is the area under the end-of-toxicity curve, TWiST is the area between the RFS and the end-of-toxicity curves, and REL is the area between the OS and RFS curves (Fig 2). Although the original report of the POG 8821 trial was based on a median follow-up of 36 months, the data set was updated to a median follow-up of 60 months (of the censoring distribution)34 for this Q-TWiST analysis. Time to end of toxicity was defined as the time from randomization until the end of the last cycle of therapy in which there was reported a symptomatic toxicity of grade
Because this study in its original design did not incorporate a QOL objective or end point, patient assessments of utility values in this study are not available. In their absence, a threshold utility analysis was performed in which all possible pairs of utility weight were evaluated to determine which treatment would be preferred for each possible set of values. To inform better the estimated weighting, particularly for the health state of CGVHD, we also reviewed the results of a study conducted at the DFCI during this same time period on the impact of BMT on children's self-reported health status. This study used the Child Health Ratings Inventories questionnaire and its disease-specific module for BMT, the Disease-Specific Impairment Inventory-BMT, to elicit information on children's self-perceptions of functional status and overall QOL.36
Two hundred thirty-two patients were randomized to either intensive chemotherapy (n = 117) or ABMT (n = 115). Eighty-nine patients were assigned to allo BMT. The incidence of grade 3 or higher toxicity for the two induction courses, which all patients received, was similar for the three treatment groups: 105 (89.8%) in the CC group; 106 (92.2%) in the ABMT group; and 85 (95.5%) in the allo BMT group. The most commonly reported toxicities (summarized in Table 1) were infections (bacterial, viral, fungal, and unknown), hemorrhage, liver, kidney/bladder, stomatitis, and cardiac. Results did not change in either the distribution or type of toxicity when a similar analysis of grade 2 or greater toxicity was performed (data not shown). Relapse occurred for 67 patients (57.3%) in the CC group, 56 patients (48.7%) in the ABMT group, and 26 patients (29.2%) in the allo BMT group. Sixty-two patients (53.0%) in the CC group, 65 (56.5%) in the ABMT group, and 33 (37.1%) in the allo BMT group died.
Figure 2 shows the partitioning of OS time into the clinical health states of TOX, TWiST, and REL according to each treatment group separately. The average number of months patients spent in the various health states during the first 60 months of follow-up, as well as the average OS and RFS, are listed in Table 2. Two pair-wise comparisons are highlighted to illustrate these results: CC versus ABMT, given the original study design, and CC versus allo BMT. No significant difference was found in the average amount of time spent in TOX between the CC and ABMT groups (a mean of 2.2 months and 2.4 months, respectively; P = .16). In contrast, patients in the allo BMT groups spent an average of 3.4 months in TOX, significantly more than either the CC or the ABMT group (P < .001). After resolution of initial treatment-related toxicity, patients in the CC group spent a mean of 27.3 months in TWiST before relapse or death occurred, compared with 25.4 months for the ABMT group; this difference of 1.9 months was not statistically significant (P = .55). The time spent in TWiST for the allo BMT group was 33.9 months for the analysis not including the health state of CGVHD, significantly more than either the CC group (P = .06) or the ABMT group (P = .02). Further, the time after relapse was 6.2 months for the CC group, 3.5 months for the ABMT subset, and 4.5 months for the allo BMT group. In summary, patients assigned to the CC group had less time in TOX and more time in TWiST, relapse-free time, and alive time than the ABMT group, although none of these differences was statistically significant. In contrast, although patients who received allo BMT spent more time in TOX than patients in the CC group, the allo BMT group also experienced more time in TWiST (P = .06), more time relapse-free (P = .03), and more time alive (P = .07) compared with the CC group. Similar findings were noted in a comparison between the allo BMT group and the ABMT group (Table 2).
The utility threshold analysis revealed that CC was preferred over ABMT for all possible utility values, although this difference was not statistically significant for any of the utility value pairs. The Q-TWiST months gained for chemotherapy ranged from 1.7 to 4.6 (Fig 3A). In contrast, the comparison of allo BMT with CC revealed a significant increase in Q-TWiST for allo BMT, based on multiple utility pairs (Fig 3B). For example, for the utility weights of 0.8 for toxicity and 0.7 for postrelapse survival, allo BMT provided 6.4 more months of Q-TWiST than chemotherapy (P = .05). Of note, time in the health state of CGVHD was not included in this comparison.
CGVHD
This Q-TWiST analysis of data from the POG 8821 study provides a comparison of quality-adjusted survival of children with newly diagnosed AML who received one of three distinct treatment modalities, randomized assignment to either intensive chemotherapy or ABMT or allo BMT from a matched related donor. This analysis shows that children treated with chemotherapy alone spent more time without symptoms than children undergoing ABMT; these differences were not statistically significant. In contrast, the Q-TWiST analysis demonstrates that allo BMT yielded significantly more quality-adjusted time than either of the other modalities for all possible combinations of utility coefficient values. The inclusion of the CGVHD health state, however, would decrease the amount of quality-adjusted time for the allo BMT group by an estimated 5.1 months and, as listed in Table 2, would reduce the net difference among the three treatment arms in terms of mean duration of time in TWiST. Nevertheless, in a threshold analysis, even when time in CGVHD was assigned a value of 0 (as bad as death), allo BMT remained the favored modality. Results from the ancillary study on children's self-reported health status after BMT would suggest that the value of time in the health state of CGVHD would not be equivalent to death. The Q-TWiST analysis, modeled from the point of randomization, is a powerful decision aid for patients and their families in choosing among alternative therapies. This approach incorporates patient preferences about the time spent in the different AML-related health states for each modality, taking into account acute and delayed toxicity and overall disease responsiveness. For example, if a patient valued time in TOX equivalent to death, the utility value for TOX would be 0, whereas if a patient wanted to avoid relapse, regardless of the toxicity, the value of uTOX would be 1 and the value of relapse would be 0. The utility coefficients represent average values of weights applied to the clinical health states. The health states could have been defined more precisely to highlight changes in utility scores over time (adaptation) or explicit differences between grade 3 and grade 4 toxicities. These models, however, would need to be calibrated carefully so that the fundamental trade-offs between major treatment categories are not obscured by excessive detail. The clinical trial data provide estimates for the clinical health state duration in the Q-TWiST analysis. Patient preference information, however, is not available from the POG study. The assignment of utility values is not required to evaluate the QOL oriented trade-offs to be considered for treatment choice. The primary Q-TWiST analysis relies on the threshold utility sensitivity analysis that allows the trade-offs between treatments to be assessed for the entire range of utility coefficients. In this way, the treatment comparison is not fixed according to any single set of utility values but can be calculated assuming a variety of perspectives (clinician, parent, child), individual personal preferences, and conditions of adaptation. Ideally, future trials will incorporate a prospective collection of information on preferences regarding trade-offs of risks and benefits from all parties. These refinements will assist us in the decision-making process regarding treatment selection in a variety of cancer scenarios. The Q-TWiST analysis performed on POG 8821 reflects the prevailing practice at the time of the trial's design, that is, to recommend allo BMT to all patients with a matched family donor. Given superior outcome for some prognostic groups (eg, initial karyotype),37-44 investigators are reevaluating the role of allo BMT for all patients at first remission, based on the notion that some patients could be cured with conventional (per primam) therapy alone. Although the benefits of this approach would require prospective randomized trials, the guiding principle would be to avoid acute and delayed toxicities of allo BMT in standard-risk or good-risk patients and to reserve allo BMT for first relapse or second remission in these patients. Ongoing studies are needed to address the value of alternative strategies for the treatment of de novo AML with emphasis on their relative impact on QOL. Prospective information on patient preferences with regard to toxicity, disease responsiveness, and site of care will facilitate the evaluation of treatment outcomes in future trials. Additional refinements in the Q-TWiST method to incorporate degree of toxicity, sites of relapsed disease, and intensity of chronic sequelae could be included to further enhance the power of this patient care decision-making tool. With wider application, this method of describing quality-adjusted survival will be useful in interpreting the results of clinical trials.
Supported by a Research Project grant no. RPG-90-013-08-PBP from the American Cancer Society and grants no. CA29139, CA23108, and CA37379 from the National Cancer Institute. Other Pediatric Oncology Group (POG) support included grants no. CA41573 (Dana-Farber), CA29293 (Massachusetts General Hospital and Dartmouth Hitchcock), CA03161 (Baylor), CA20549 (Emory), and CA29691 (Children's Hospital of Michigan). A full list of institutions participating in POG in protocol 8821 is listed in the Appendix. S.K.P. is a Dyson Scholar in Clinical Research at the Dana-Farber Cancer Institute. The authors are appreciative of the stalwart support and inspiration of Drs Emil Frei and David Nathan in the development of this manuscript. We also thank Dr Marco Bonetti for technical assistance with the Q-TWiST threshold utility plots.
A preliminary report on this study was presented at the July 1997 Joint Meeting of the Society for Clinical Trials and International Society for Clinical Biostatistics, Boston, MA.
1. Woods WG, Kobrinsky N, Buckley J, et al: Intensively timed induction therapy followed by autologous or allogeneic bone marrow transplantation for children with acute myeloid leukemia or myelodysplastic syndrome: A Children's Cancer Group pilot study. J Clin Oncol 11:1448-1457, 1993
2.
Rowe JM, Tallman MS: Intensifying induction therapy in acute myeloid leukemia: Has a new standard of care emerged? Blood 90:2121-2126, 1997
3.
Creutzig U, Ritter J, Riehm H, et al: Improved treatment results in childhood acute myelogenous leukemia: A report of the German Cooperative Study AML-BFM-78. Blood 65:298-304, 1985 4. Vormoor J, Boos J, Stahnke K, et al: Therapy of childhood acute myelogenous leukemia. Ann Hematol 73:11-24, 1996[Medline] 5. Nesbit ME Jr Buckley JD, Feig SA, et al: Chemotherapy for induction of remission of childhood leukemia followed by bone marrow transplantation or multiagent chemotherapy: A report from the Children's Cancer Group. J Clin Oncol 12:127-135, 1994[Abstract]
6.
Wells RJ, Woods WG, Buckley JD, et al: Treatment of newly diagnosed children and adolescents with acute myeloid leukemia: A Children's Cancer Group Study. J Clin Oncol 12:2367-2377, 1994 7. Feig SA, Lampkin B, Nesbit ME, et al: Outcome of BMT during first complete remission of AML: A comparison of two sequential studies by the Children's Cancer Group. Bone Marrow Transplant 12:65-71, 1993[Medline] 8. Dinndorf P, Bunin N: Bone marrow transplantation for children with acute myelogenous leukemia. J Pediatr Hematol Oncol 17:211-224, 1995[Medline]
9.
McGlave PB, Haake RJ, Bostrom BC, et al: Allogeneic bone marrow transplantation for acute nonlymphocytic leukemia in first remission. Blood 72:1512-1517, 1988 10. Dini G, Abla O, Uderzo C, et al: Allogeneic bone marrow transplantation in children with AML: Italian experience. Bone Marrow Transplant 7:76-77, 1991 (suppl 3) 11. Dahl GV, Kalwinsky DK, Mirro J Jr et al: Allogeneic bone marrow transplantation in a program of intensive sequential chemotherapy for children and young adults with acute nonlymphocytic leukemia in first remission J Clin Oncol 8:295-303, 1990[Abstract] 12. Michael G, Gluckman E, Blaise D, et al: Improvement in outcome for children receiving allogeneic bone marrow transplantation in first remission of acute myeloid leukemia: A report from the Groupe D'etude Des Greffes De Moelle Osseuse. J Clin Oncol 10:1865-1869, 1992[Abstract] 13. Santos GW, Tutschka PJ, Brookmeyer R, et al: Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med 309:1347-1353, 1983[Abstract]
14.
Amadori S, Testi AM, Arico M, et al: Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. J Clin Oncol 11:1046-1054, 1993 15. Lowenberg B, Verdonck LJ, Dekker AW, et al: Autologous bone marrow transplantation in acute myeloid leukemia in first remission: Results of a Dutch prospective study. J Clin Oncol 8:287-294, 1990[Abstract]
16.
Zittoun RA, Mandelli F, Willemze R, et al: Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med 332:217-223, 1995
17.
Appelbaum RA, Fisher LD, Thomas D: Chemotherapy v marrow transplantation for adults with acute nonlymphocytic leukemia: A five-year follow-up—Seattle Marrow Transplant Team. Blood 72:179-184, 1988
18.
Mayer RJ: Allogeneic transplantation versus intensive chemotherapy in first-remission acute leukemia: Is there a "best choice?" J Clin Oncol 6:1532-1536, 1988 19. Begg CB, McGlave PB, Bennett JM, et al: A critical comparison of allogeneic bone marrow transplantation and conventional chemotherapy as treatment for acute nonlymphocytic leukemia. J Clin Oncol 2:369-378, 1984[Abstract]
20.
Petersen FB, Lynch MHE, Clift RA, et al: Autologous marrow transplantation for patients with acute myeloid leukemia in untreated first relapse or in second complete remission. J Clin Oncol 11:1353-1360, 1993 21. Reiffers J, Gaspard MH, Maraninchi D, et al: Comparison of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukaemia in first remission: A prospective control trial. Br J Haematol 72:57-63, 1989[Medline]
22.
Harousseau J-L, Cahn J-Y, Pignon B, et al: Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy for adult acute myeloid leukemia. Blood 90:2978-2986, 1997 23. Vowels M, Stevens M, Tiedemann K, et al: Autologous and allogeneic bone marrow transplantation for childhood acute nonlymphoblastic leukemia. Transplant Proc 24:184-185, 1992[Medline] 24. Hermans J, Suciu S, Stijnen TH, et al: Treatment of acute myelogenous leukemia: An EBMT-EORTC retrospective analysis of chemotherapy versus allogeneic or autologous bone marrow transplantation. Eur J Clin Oncol 25:545-550, 1989
25.
Ravindranath Y, Yeager AM, Chang MN, et al: Autologous bone marrow transplantation versus intensive chemotherapy for acute myeloid leukemia in childhood. N Engl J Med 334:1428-1434, 1996 26. Goldhirsch A, Gelber RD, Simes RJ, et al: Costs and benefits of adjuvant therapy for breast cancer: A quality-adjusted survival analysis. J Clin Oncol 7:36-44, 1989[Abstract]
27.
Gelber RD, Goldhirsch A, Cole BF, et al: A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of adjuvant radiation therapy and chemotherapy for resectable rectal cancer. J Natl Cancer Inst 88:1039-1045, 1996
28.
Lenderking WR, Gelber RD, Cotton DJ, et al: Evaluation of the quality of life associated with zidovudine treatment in asymptomatic human immunodeficiency virus infection. N Engl J Med 330:738-743, 1994
29.
Cole BF, Gelber RD, Kirkwood JM, et al: Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: An Eastern Cooperative Oncology Group study. J Clin Oncol 14:2666-2673, 1996 30. Ogden AK, Parsons SK, Ravindranath Y, et al: Busulfan and cyclophosphamide conditioning for allogeneic transplantation in children with acute myelogenous leukemia in first complete remission. J Cell Biochem Suppl 18B:64, 1986 (abstr) 31. Ferrant A, Doyen C, Delannoy A, et al: Allogeneic or autologous bone marrow transplantation for acute non-lymphocytic leukemia in first remission. Bone Marrow Transplant 7:303-309, 1991[Medline]
32.
Sierra J, Brunet S, Granena A, et al: Feasibility and results of bone marrow transplantation after remission induction and intensification chemotherapy in de novo acute myeloid leukemia. J Clin Oncol 14:1353-1363, 1996 33. Shulman HM, Sullivan KM, Weiden PL, et al: Chronic graft versus host syndrome in man: A long-term clinico-pathologic study of 20 Seattle patients. Am J Med 69:204-217, 1980[Medline]
34.
Shuster JJ: Median follow-up in clinical trials. J Clin Oncol 9:191-192, 1989 35. Gelber RD, Cole BF, Gelber S, et al: Comparing treatments using quality-adjusted survival: The Q-TWiST method. Am Statist 49:161-169, 1995 36. Kaplan SH, Barlow SE, Parsons S, et al: Assessing functional status and health-related quality of life among school-aged children: Reliability and validity of a new self-reported measure. International Society for Quality of Life Research, Montreal, Canada, October 1995 (abstr presentation) 37. Fenaux P, Preudhomme C, Lai JL, et al: Cytogenetics and their prognostic value in de novo acute myeloid leukaemia: A Report on 283 Cases. Br J Haematol 73:61-67, 1989[Medline] 38. Arthur DC, Berger R, Golomb HM, et al: The clinical significance of karyotype in acute myelogenous leukemia. Cancer Genet Cytogenet 40:203-216, 1989[Medline] 39. Stasi R, Del Poeta G, Masi M, et al: Incidence abnormalities and clinical significance of karyotype in de novo acute myeloid leukemia. Cancer Genet Cytogenet 67:28-34, 1993[Medline] 40. Marosi C, Koller U, Koller-Weber E, et al: Prognostic impact of karyotype and immunologic phenotype in 125 adult patients with de novo AML. Cancer Genet Cytogenet 61:14-25, 1992[Medline] 41. Marlton P, Keating M, Kantarjian H, et al: Cytogenetic and clinical correlates in AML patients with abnormalities of chromosome 16. Leukemia 9:965-971, 1995[Medline] 42. Swansburry GJ, Lawler SD, Alimena G, et al: Long-term survival in acute myelogenous leukemia: A second follow-up of the Fourth International Workshop on Chromosomes in Leukemia. Cancer Genet Cytogenet 73:1-7, 1994[Medline]
43.
Ferrant A, Labopin M, Frassoni F, et al: Karyotype in acute myeloblastic leukemia: Prognostic significance for bone marrow transplantation in first remission—A European Group for Blood and Marrow Transplantation study. Blood 90:2931-2938, 1997 44. Gale RP, Horowitz MM, Weiner RS, et al: Impact of cytogenetic abnormalities on outcome of bone marrow transplants in acute myelogenous leukemia in first remission. Bone Marrow Transplant 16:203-208, 1995[Medline] Submitted September 21, 1998; accepted March 9, 1999.
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 1999 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
3 severity; TWiST, the period representing the best possible QOL after the diagnosis of AML, during which patients experience no toxicities of treatment or symptoms of disease; and REL, all time after disease relapse. The TOX period was defined to include only categories of toxicity assumed by the clinicians as having a functional impact on the patient. 
