This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kiss, T.L. Articles by Messner, H.A. Search for Related Content PubMed PubMed Citation Articles by Kiss, T.L. Articles by Messner, H.A. Social Bookmarking                            What's this?

Long-Term Medical Outcomes and Quality-of-Life Assessment of Patients With Chronic Myeloid Leukemia Followed at Least 10 Years After Allogeneic Bone Marrow Transplantation

From the Bone Marrow Transplant Service, Department of Medical Oncology and Hematology, Princess Margaret Hospital/University Health Network, and the Population Health Sciences Research Institute, The Hospital for Sick Children and Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada.

Address reprint requests to T.L. Kiss, MD, Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Ave, Toronto, Ontario M5G 2M9, Canada; email: thomas.kiss@ uhn.on.ca.

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: Benchmark analysis of patients with chronic myeloid leukemia (CML) alive for more than 10 years after allogeneic bone marrow transplantation (BMT) including data on disease status, bone marrow reserve, long-term complications, and quality of life (QOL).

PATIENTS AND METHODS: Eighty-nine patients (46 in first chronic phase, 43 in advanced phase) received an allogeneic BMT for CML during the study period. Medical outcomes and QOL of patients were analyzed retrospectively.

RESULTS: Twenty-eight (31.5%) of 89 patients were alive at 10 years and included in this analysis. Thirteen (46.4%) of 28 long-term survivors never relapsed. Fifteen patients relapsed between 0.5 and 16 years after transplantation. Ten patients showed a hematologic relapse and received salvage treatment. Five patients showed transient low levels of BCR-ABL–positive cells by Southern blot with no subsequent hematologic relapse. One of the 28 patients died in blast crisis at 12 years. The most frequent long-term complications were chronic graft-versus-host disease, osteoporosis, and cataracts. Frequency of clonogenic progenitors remained persistently decreased. QOL assessment yielded lower scores in physical performance as compared with an age-matched normative population, whereas social functioning was equivalent. A high degree of satisfaction was noted with interpersonal relationships.

CONCLUSION: Patients with CML surviving their BMT long term do well in terms of medical outcomes. A constant rate of relapse was noted, with a high salvage rate of affected patients, suggesting the need for lifelong monitoring. QOL is perceived as good, particularly as related to social functioning; however, it is inferior to a normative population with regard to physical performance.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
ALLOGENEIC SIBLING donor bone marrow transplantation (BMT) is an established treatment modality for patients with chronic myeloid leukemia (CML), yielding satisfactory disease control and overall survival (OS) of affected patients.^1,2 Multiple studies have been published on short-term outcomes of patients with CML.^3-6 As long-term survivors of BMT become more numerous, studies mainly originating from two groups, Seattle and the European Group for Blood and Marrow Transplantation (EBMT), have addressed the issue of long-term follow-up of these patients.^7-10 In the original study of the EBMT, outcomes were presented on related and unrelated marrow recipients who received their transplantation between 1979 and 1990.⁷ This study reported an OS of 47% at 8 years in 947 patients who underwent transplantation in first chronic phase (CP1) from an HLA-identical sibling donor. A subset of patients who had received standard graft-versus-host disease (GVHD) prophylaxis using cyclosporine and methotrexate (n = 238) experienced an OS of 64% at 8 years. Age, T-cell depletion of donor marrow, time from diagnosis to transplantation longer than 1 year, high WBC count at diagnosis, and donor recipient sex combination (female donor/male recipient) were identified as unfavorable prognostic factors. Two follow-up articles were published more recently. At 10 years, 39% of all patients who underwent transplantation for CML by the EBMT were alive (n = 2,942).^8,9 Median survival for those patients who underwent transplantation in CP1 from a related sibling donor with a non–T-cell–depleted bone marrow at 10 years was not reached and exceeded 55%. The Seattle experience of BMT in CML is summarized in a study published in 1996.¹⁰ At that time, 39 patients (19.7%) who underwent transplantation for CML until 1983 were alive and in remission 10 years or more after their transplantation. Patients who underwent transplantation in CP1 had better survival than those who underwent transplantation with more aggressive disease.

Quality of life (QOL) is an important subjective outcome measure of BMT. Multiple studies have reported on QOL issues in BMT patients using different methods of assessment.^10-19 Most of these studies were cross-sectional in design, using a number of instruments.^20-23

Comparison of QOL data in post-BMT patients with a reference population in Britain found most important differences for physical mobility, work, and sex life, with a median follow-up of 55 months after transplantation.¹³ In this work, a high systemic symptomatology score, a shorter time after transplantation, female sex, and impotence were significantly associated with an impaired overall QOL. A lower level of education appeared a significant predictor of an impaired QOL in contrast to another study.¹⁴ Other studies, including one from this institution, confirm the notion that decreased QOL was noted in patients who more recently underwent transplantation^15-17 and that long-term survival is associated with improved QOL.¹⁸ In a study of 125 adult BMT patients with a mean of 10 years after their transplantation, 74% judged their current QOL to be the same or better as before the transplantation.¹⁹ Long-term survivors continued to experience a moderate incidence of complications, including emotional and sexual dysfunction, fatigue, eye problems, sleep disturbance, general pain, and cognitive dysfunction. The severity of these symptoms was assessed as low.

In this study, we report on relapse and survival data, progenitor cell analysis, and QOL information derived from health-related quality-of-life (HQL) analysis on CML patients who survived a BMT for at least 10 years. Medical outcomes include current disease control and comorbidity of patients. Laboratory data on hemopoietic reserve as assessed by in vitro bone marrow culture assays are reviewed. The impact of objective measures on QOL is analyzed.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Study Design and Patients
This study is a retrospective analysis of all CML patients who underwent transplantation at Princess Margaret Hospital from January 1, 1979, to March 10, 1988, that have survived for at least 10 years after transplantation. Eighty-nine patients with CML underwent transplantation at Princess Margaret Hospital during that time period, 46 in chronic phase and 43 with more advanced disease. Twenty-eight patients who received a matched-sibling donor transplantation (31.5%) were alive at 10 years or longer. Medical data were collected by chart review and a regularly updated computer database. HQL data were obtained by analysis of patient responses to mailed questionnaires.¹⁷ Twenty-six (93%) of 28 patients responded. One patient died before the questionnaire could be answered. Another patient chose not to participate in the survey.

Transplantation Procedure
Twenty seven patients were prepared with a continuous intravenous infusion of cytarabine at 100 mg/m² on day -8 to day -4, followed by cyclophosphamide 60 mg/kg intravenously on days -3 and -2. Total-body irradiation was administered as a single fraction of 5 Gy at a dose rate of 0.4 to 0.9 Gy/min²⁴ on day 0 before bone marrow infusion. One patient received busulfan 1 mg/kg orally every 6 hours from day -7 to day -4 followed by cyclophosphamide 60 mg/kg intravenously on days -3 and -2. ABO-incompatible donor-recipient pairs were managed by either plasmapheresis or red cell depletion of donor bone marrow.

GVHD prophylaxis was used according to the protocol active at the time of the patient’s transplantation and included, initially, methotrexate at the standard dose of 15 mg/m² on day 1 followed by 10 mg/m² on days 3, 6, and 11 and weekly thereafter until day 100,²⁵ and later on methotrexate and prednisone (n = 16). Since 1986, standard cyclosporine and methotrexate²⁶ have been used (n = 12). T-cell depletion was not performed.

Trimethoprim/sulfamethoxazole starting on the first day of conditioning was given until recovery of neutrophil counts. Trimethoprim/sulfamethoxazole was used after day 28 for Pneumocystis carinii prophylaxis unless allergy developed.

Patients were assessed on an annual basis for long-term complications and had referrals to ophthalmology and bone density measurements when clinically appropriate. Screening for hypothyroidism was performed on a routine basis using laboratory methods at the time of the annual visit. All patients were followed at our transplantation center long term.

Bone Marrow In Vitro Culture
Bone marrow cells were cultured for colony growth according to previously published methods using human plasma and medium conditioned by phytohemagglutinin-stimulated leukocytes.²⁷

Molecular Testing
Southern blotting and reverse transcriptase polymerase chain reaction (RT-PCR) were performed according to previously published methods.²⁸ Level of sensitivity of the Southern blot assay used was 5%. Disease relapse was defined as occurrence of the BCR-ABL fusion gene determined by Southern blotting, cytogenetics, and/or presence of classical hematologic changes.

HQL Assessment
Patients were mailed a questionnaire to assess HQL. This included the Medical Outcomes Survey Short Form 36 (MOS SF-36),^20-23 the Satisfaction with Life Domain Scale Bone Marrow Transplantation (SLDS-BMT),²⁹ and the Princess Margaret Hospital Symptom Experience Report (PMH-SER).¹⁷

The MOS SF-36 survey. This tool measures HQL outcomes, mainly those known to be most directly affected by disease and treatment such as functional status and well-being.²³ The questionnaire has eight domains containing two to 10 items each for a total of 36 questions. The domains include physical functioning, role functioning-physical, role functioning-emotional, social functioning, bodily pain, mental health, vitality, and general health. Raw scale scores are calculated and then transformed to a scale ranging from 0 to 100. No total score is generated, but each of the eight domains has a summary score. Higher scores indicate better HQL. The questionnaire has been validated and is used in several languages.²³

The SLDS-BMT. Eighteen domains are assessed by this questionnaire. They include aspects of most life situations and areas of life that can be affected by cancer and its treatment. Assessment of satisfaction with such factors as relationships, health, appearance, leisure time, ability to eat, physical strength, and BMT are obtained. Ratings are made on a seven-point scale that has seven faces ranging from extremely happy to extremely unhappy (broadly downturned mouth). The items are summed to give an overall score. Higher scores indicate greater satisfaction. Evidence of internal consistency, sensitivity, and validity have been demonstrated previously.^29,30

The PMH-SER. In the first part, a checklist was used to elicit data on 23 symptoms commonly associated with BMT. These were rated on a four-point severity scale. The items contained in the checklist were generated from clinical experience and the literature. In the second part, patients were asked to rate the impact of their present health condition on their ability to work at their usual performance level and whether they were able to reach their educational goals and usual work activities in the 4 weeks before completion of the questionnaire. Choices were no, mild, moderate, or severe limitations. The survey tool was developed at Princess Margaret Hospital and has not received psychometric testing. It has been applied in a previously published HQL survey on patients after BMT at our institution.¹⁷

Statistical Analysis
Descriptive statistics were used to summarize the scores for MOS SF-36 subscales, the SLDS-BMT questionnaire, and the PMH-SER. Comparisons between MOS SF-36 patient data and normative data were performed using the unpaired two-sample t test for unequal variances; data on four norm age groups of 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years were used.

The ² test statistic³¹ was used to assess association between transplantation parameters and QOL domains. In addition, multivariate analysis of variance was used to assess the effects of demographic and disease-related parameters on QOL domains as measured by the MOS SF-36.

Analysis of in vitro colony data was performed using an unpaired two-sample t test for unequal variances. Kaplan-Meier survival curves³² were generated for OS and relapse-free survival of CML long-term survivors.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Medical Outcomes
Clinical outcomes. Eighty-nine patients with CML underwent transplantation during the study period. Of these patients, 46 underwent transplantation in CP1 and 43 in a more advanced phase of their disease. Of the 46 patients who underwent transplantation in CP1, 23 were alive (50.0%) at study closure and four (9.3%) of the 43 patients had more advanced disease.

Twenty-eight (31.5%) of 89 patients were alive 10 or more years after their BMT and were included in this study. Twenty-four were in CR1, and four patients were in a more advanced phase at BMT. The median follow-up of patients is 12.6 years, with a range of 10.4 to 18.7 years. Characteristics of these patients are listed in Table 1. The median age of patients was 33.1 years, with 16 male and 12 female patients. Mean time from disease diagnosis to date of transplantation was 2.3 years. Nine patients underwent transplantation within the first year after diagnosis. Sixteen patients did not receive cyclosporine as part of their GVHD prophylaxis. Eleven patients presented with a leukocyte count of more than 100 x 10⁹/L. Fourteen (50%) had splenomegaly, 15 (53.6%) had an elevated platelet count, and 12 (42.9%) had evidence for basophilia at diagnosis. Donor-recipient sex ratio was also analyzed. Thirteen patients (six female) underwent transplantation from a female donor and 15 (nine male) from a male.

Mean time to hematologic or cytogenetic relapse was 7.7 years, with a median of 8 years. Five patients relapsed more than 10 years after their transplantation. Median follow-up of patients after relapse was 6.2 years. The probability for relapse-free survival of patients on the basis of hematology and Southern blotting at a given time is depicted in Fig 1. OS of these patients is shown in Fig 2. Of note is that the rate of decline of the relapse-free survival probability appeared to be constant over the observed period of 20% every 5 years.

View larger version (8K): [in this window] [in a new window]   Fig 1. Probability of relapse-free survival as calculated by the Kaplan-Meier method.

View larger version (7K): [in this window] [in a new window]   Fig 2. Probability of OS as calculated by the Kaplan-Meier method.

GVHD and long-term complications. A history of acute grade II to IV GVHD was seen in 53.6% of the study patients. The remainder of the patients had no or only mild acute GVHD (grade 0 to I). Chronic GVHD at the time of evaluation was present in nine patients, extensive in five and limited in four. These data are listed in Table 2. The cumulative rate for chronic GVHD was 64.3%.

A survey was taken of medications used by the study population at the time of assessment. These results are listed in Table 3. Nine patients did not use any medications on a regular basis. Seven patients were on hormone replacement, four were on prophylactic antibiotics, and four were on antihypertensive drugs. Three patients were on immune suppressants, including cyclosporine, prednisone, and azathioprine for treatment of persisting chronic GVHD (10.7%).

To achieve an estimate on progenitor cell reserve in posttransplantation patients, bone marrow was cultured in vitro under previously described culture conditions.²⁵ Most donor bone marrow samples collected before the transplantation yielded excellent growth of hemopoietic precursor colonies when cultured under standard culture conditions, including colony-forming unit–granulocyte-erythrocyte-megakaryocyte-macrophage, –megakaryocyte, –granulocyte-macrophage, and burst-forming unit–erythrocyte (Table 4). Bone marrow derived from patients at various intervals after transplantation yielded statistically significantly lower mean numbers of hemopoietic precursor colonies when compared with the mean values of corresponding donor marrow-derived colonies before transplantation. This decrease affected all lineages and was sustained for 10 or more years after transplantation.

QOL Outcomes
HQL was assessed by questionnaires comparing three different instruments that were mailed to patients. A majority of surviving patients (96.3%) responded.

MOS SF-36. The MOS SF-36 survey measures functional status and well-being, assessing HQL that is not treatment specific.²³ In the study population, three domains scored lower as compared with an age-adjusted normative population at a level of P < .05. These include physical functioning (P = .025), role functioning-physical (P = .019), and general health (P = .0019). These domains describe mainly physical functions. Other domains characterizing social functions were found to be equivalent when comparing study patients with the normative population. Figure 3 illustrates the means and standard errors of the eight MOS SF-36 subscales for the American general population of males and females (aged 18 to 54 years) compared with study patients.

View larger version (53K): [in this window] [in a new window]   Fig 3. Comparison between CML patients and United States population norms for eight QOL domains as measured by the MOS SF-36. Mean scores with standard errors are shown. BMT, bone marrow transplant patients; NORM, age-adjusted normative population. *Comparison between patient data and normative group statistically significantly different (P < .05).

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Survival after BMT has increased with more effective GVHD prophylaxis and treatment, management of opportunistic infections, and improved supportive care. In the present study, we report on patients with CML who have survived their BMT for more than 10 years and have investigated medical outcomes and their QOL.

Twenty-eight patients were identified at our institution as having fulfilled these criteria. Most underwent transplantation in CR1; however, four had more aggressive disease at the time of their transplantation. A majority of patients underwent transplantation at a time when cyclosporine was not yet used for GVHD prophylaxis. Most patients were well at the time of evaluation in terms of their medical condition, with 33.3% having residual symptoms of chronic GHVD. Long-term transplantation-related complications were hypothyroidism, cataract formation, or development of secondary malignancies. Osteoporosis was noted in more than one third of female patients and in none of the male patients of this group. These data emphasize the importance of screening for osteoporosis as part of long-term follow-up, particularly in female patients. Nine patients were on no regular medications at the time of evaluation. Three continued to require immunosuppressive therapy.

Ten patients showed a hematologic relapse during their course after BMT and were treated with various means including second BMT, interferon, and DLI. At the time of evaluation, 27 of 28 patients were in hematologic and molecular remission as determined by Southern blotting. One patient died after development of blast crisis.

Of note is that relapses occurred during the entire period of follow-up, with a significant number more than 10 years after BMT. The rate of decline of the relapse-free survival probability appeared constant over time, 20% every 5 years, suggesting that allogeneic transplantation did not cure CML in these patients but led to long-term disease control, with minimal residual disease leading to relapse. Furthermore, these data suggest that although a significant number of patients relapsed, ultimately excellent long-term survival could be achieved after transplantation because this disease remained sensitive to immune modulatory salvage interventions such as DLI, interferon, and/or second BMT. Because of the high success rate of secondary therapy in the situation of relapse after BMT, lifelong regular molecular monitoring of these patients is mandatory. This can be achieved by using either peripheral blood or bone marrow samples.³³

Hemopoietic progenitor cell presence and function was assessed by in vitro culture methods.²⁵ Results showed that despite a majority of patients having normal peripheral blood counts, the number of progenitor colonies derived from recipients’ bone marrow remained persistently lower in all lineages as compared with colony numbers derived from the corresponding normal donor bone marrow before transplantation. This may indicate a persistently decreased bone marrow progenitor cell reserve in terms of numbers and/or differentiating capability of progenitor cells after BMT.

QOL measurements allow patients to express directly how they perceive their present and past health condition. This provides health care providers with valuable tools on how to direct patient care. A recently published study conducted at our institution including BMT patients with a number of diagnoses reported that QOL was perceived to be inferior as compared with a normative group in the first 3 years after the transplantation. However, patients more than 3 years after their transplantation scored the same or in some domains even higher values as a normative population.¹⁷ In contrast, patients in this study scored lower than the standard population when using the MOS SF-36 in three out of eight domains. These domains relate mainly to physical performance. In all other domains related to social functioning, there were no differences between the normative group and study patients, suggesting that in this group of patients decreased physical performance impacted negatively on QOL, whereas social functioning was well preserved. Perhaps difficulties of the peritransplantation period and the immediate goal of surviving a difficult treatment were too remote, leading to a higher significance of bodily symptoms. Unlike patients with acute leukemia, patients with CML were generally well at the time of transplantation and hence may have had expectations different from other transplantation patients.

A number of medical outcomes were significantly associated and predictive for a decreased QOL. Acute or chronic GVHD impacted on long-term QOL. Many patients of this study underwent transplantation in the precyclosporine era, when GVHD occurred more frequently. Experiencing a previous relapse impacted mainly on the emotional level. Presence of osteoporosis or having to take medications also decreased QOL. Splenomegaly at the time of diagnosis was a significant predictor of decreased QOL. This may be related to the notion that splenomegaly can be a marker of more aggressive disease.

Analysis of satisfaction of life domain scales showed a high satisfaction of patients with their BMT and with interpersonal relationships and their overall QOL. Demographic analysis of patients did not show any difference as to how questionnaires were answered. The PMH-SER showed the presence of five symptoms to be bothersome to more than 20% of respondents, including eye dryness, poor memory, fatigue, pain, and joint stiffness, suggesting that these symptoms may explain why some patients perceived their physical performance as inferior long-term. Having identified these problems, strategies should be sought to improve on these aspects in order to further enhance QOL of long-term transplantation survivors.

In summary, patients with CML having survived their BMT for more than 10 years did generally well in terms of their medical outcomes. A constant number of late relapses over time were noted, with most relapsed patients being salvaged. Therefore, lifelong regular molecular monitoring is recommended. Progenitor cell numbers remained low long-term, indicating the possibility of decreased bone marrow reserve. QOL was generally perceived as good, particularly as related to social functioning; however, it was inferior in physical domains as compared with a normative control group.

	ACKNOWLEDGMENTS

 
Laboratory aspects of this study were supported by grant no. MT6413 from the Medical Research Council of Canada, Ottawa, Ontario, Canada.

We thank all health care professionals and support staff caring for allogeneic transplantation patients at Princess Margaret Hospital for their dedication and work.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
1. Appelbaum FR, Clift R, Radich J, et al: Bone marrow transplantation for chronic myelogenous leukemia. Semin Oncol 22: 405-411, 1995[Medline]

2. Kantarjian HM, O’Brien S, Anderlini P, et al: Treatment of chronic myeloid leukemia: Current status and investigational options. Blood 87: 3069-3081, 1996[Free Full Text]

3. Horowitz MM, Rowlings PA, Passweg JR: Allogeneic bone marrow transplantation for CML: A report from the International Bone Marrow Transplant Registry. Bone Marrow Transplant 17: S5-S6, 1996 (suppl 3)

4. Moreb J, Johnston T, Kubilis P, et al: Improved survival of patients with chronic myelogenous leukemia undergoing allo-geneic bone marrow transplantation. Am J Hematol 5: 304-306, 1995

5. Devergie A, Blaise D, Attal M, et al: Allogeneic bone marrow transplantation for chronic myeloid leukemia in first chronic phase: A randomized trial of busulfan-cytoxan versus cytoxan-total body irradiation as preparative regimen: A report from the French Society of Bone Marrow Graft (SFGM). Blood 85: 2263-2268, 1995[Abstract/Free Full Text]

6. Lamparelli T, Van Lint MT, Gualandi F, et al: Bone marrow transplantation for chronic myeloid leukemia from unrelated and sibling donors: Single center experience. Bone Marrow Transplant 20: 1057-1062, 1997[CrossRef][Medline]

7. Gratwohl A, Hermans J, Niederwieser D, et al: Bone marrow transplantation for chronic myeloid leukemia: Long term results. Bone Marrow Transplant 12: 509-516, 1993[Medline]

8. van Rhee F, Szydlo RM, Hermans J, et al: Long term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: A report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 20: 553-560, 1997[CrossRef][Medline]

9. Gratwohl A, Hermans J: Allogeneic bone marrow transplantation for chronic myeloid leukemia. Bone Marrow Transplant 17: S7-S9, 1996 (suppl 3)

10. Clift RA, Storb R: Marrow transplantation for CML: The Seattle experience. Bone Marrow Transplant 17: S1-S3, 1996 (suppl 3)

11. McQuellon RP, Russell GB, Cella DF, et al: Quality of life measurement in bone marrow transplantation: Development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Scale. Bone Marrow Transplant 19: 357-368, 1997[CrossRef][Medline]

12. Grant M, Ferrell B, Schmidt GM, et al: Measurement of quality of life in bone marrow transplantation survivors. Qual Life Res 1: 375-384, 1992[CrossRef][Medline]

13. Prieto JM, Saez R, Carreras E, et al: Physical and psychosocial functioning of 117 survivors of bone marrow transplantation. Bone Marrow Transplant 17: 1133-1142, 1996[Medline]

14. Litwins NM, Rodriguez JR, Weiner RS, et al: Quality of life in adult recipients of bone marrow transplantation. Psychol Rep 75: 323-328, 1994[Medline]

15. Kopp M, Schweigkofler H, Holzner B, et al: Time after bone marrow transplantation as an important variable for quality of life: Results of a cross sectional investigation using two different instruments for quality of life assessment. Ann Hematol 77: 27-32, 1998[CrossRef][Medline]

16. McQuellon RP, Russell GB, Rambo TD, et al: Quality of life and psychological distress of bone marrow transplant recipients: The time trajectory to recovery over the first year. Bone Marrow Transplant 21: 477-486, 1998[CrossRef][Medline]

17. Sutherland HJ, Fyles GM, Adams G, et al: Quality of life following bone marrow transplantation: A comparison of patient reports with population norms. Bone Marrow Transplant 19: 1129-1136, 1997[CrossRef][Medline]

18. Molassiotis A, van den Akker OB, Milligan DW, et al: Quality of life in long term survivors of marrow transplantation: Comparison with a matched group receiving maintenance chemotherapy. Bone Marrow Transplant 17: 249-258, 1996[Medline]

19. Bush NE, Haberman M, Donaldson G, et al: Quality of life of 125 adults surviving 6-18 years after bone marrow transplantation. Soc Sci Med 40: 479-490, 1995

20. Ware JE, Sherbourne CD: The MOS 36-item short form health survey (SF-36): I. Conceptual framework and item selection. Med Care 30: 473-483, 1992[Medline]

21. McHorney CA, Ware JE Jr, Razcek AE: The MOS 36-item short form health survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 31: 247-263, 1993[Medline]

22. McHorney CA, Ware JE Jr, Lu JFR, et al: The MOS 36-item short form health survey (SF-36): III. Tests of data quality, scaling assumptions and reliability across diverse patient groups. Med Care 32: 40-66, 1994[Medline]

23. Ware JE: SF-36 Health Survey: Manual and Interpretation Guide. Boston, MA, The Health Institute, New England Medical Centre, 1993

24. Fyles GM, Messner HA, Lockwood G, et al: Long term results of bone marrow transplantation for patients with AML, ALL and CML prepared with single dose total body irradiation of 500cGy delivered with a high dose rate. Bone Marrow Transplant 8: 453-463, 1991[Medline]

25. Sullivan KM, Storb R, Buckner CD: Graft versus host disease as adoptive immunotherapy in patients with advanced hematological neoplasms. N Engl J Med 320: 828-834, 1989[Abstract]

26. Storb R, Deeg HJ, Whitehead J: Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 314: 729-735, 1984[Abstract]

27. Messner HA, Curtis JE, Minden MD, et al: Clonogenic hemopoietic precursors in bone marrow transplantation. Blood 70: 1425-1432, 1987[Abstract/Free Full Text]

28. Xu WM, Piao XH, Addy L, et al: Minimal residual disease in bone marrow transplant recipients with chronic myeloid leukemia. Bone Marrow Transplant 14: 299-306, 1994[Medline]

29. Baker F, Curbow B, Wingard JR: Development of the satisfaction with life domains scale for cancer. J Psychosoc Oncol 10: 75-90, 1992[CrossRef]

30. Baker F, Curbow B, Wingard JR: Role retention and quality of life of bone marrow transplant survivors. Soc Sci Med 32: 697-704, 1991

31. Bahn AK. Chi square test, in Basic Medical Statistics. New York, NY, Grune & Stratton, 1972, pp 63-73

32. Kaplan EI, Meier P: Non parametric estimation from incomplete observations. J Am Stat Assoc 53: 457-481, 1958[CrossRef]

33. Kiss TL, Xu WM, Jamal N, et al: Comparative testing of peripheral blood and bone marrow for BCR-ABL transcripts in patients post allogeneic bone marrow transplantation and during interferon treatment for chronic myeloid leukemia. Leuk Lymphoma 34: 493-500, 1999[Medline]

Submitted June 15, 2001; accepted February 19, 2002.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				D. Gallardo, R. de la Camara, J. B. Nieto, I. Espigado, A. Iriondo, A. Jimenez-Velasco, C. Vallejo, C. Martin, D. Caballero, S. Brunet, et al. Is mobilized peripheral blood comparable with bone marrow as a source of hematopoietic stem cells for allogeneic transplantation from HLA-identical sibling donors? A case-control study Haematologica, September 1, 2009; 94(9): 1282 - 1288. [Abstract] [Full Text] [PDF]

				J. Pidala, C. Anasetti, and H. Jim Quality of life after allogeneic hematopoietic cell transplantation Blood, July 2, 2009; 114(1): 7 - 19. [Abstract] [Full Text] [PDF]

				D. Messerer, J. Engel, J. Hasford, M. Schaich, G. Ehninger, C. Sauerland, T. Buchner, A. Schumacher, R. Krahl, D. Niederwieser, et al. Impact of different post-remission strategies on quality of life in patients with acute myeloid leukemia Haematologica, June 1, 2008; 93(6): 826 - 833. [Abstract] [Full Text] [PDF]

				C. J. Fraser, S. Bhatia, K. Ness, A. Carter, L. Francisco, M. Arora, P. Parker, S. Forman, D. Weisdorf, J. G. Gurney, et al. Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study Blood, October 15, 2006; 108(8): 2867 - 2873. [Abstract] [Full Text] [PDF]

				A. Quintas-Cardama and J. E. Cortes Chronic Myeloid Leukemia: Diagnosis and Treatment Mayo Clin. Proc., July 1, 2006; 81(7): 973 - 988. [Abstract] [Full Text] [PDF]

				K. L. Syrjala, S. L. Langer, J. R. Abrams, B. E. Storer, and P. J. Martin Late Effects of Hematopoietic Cell Transplantation Among 10-Year Adult Survivors Compared With Case-Matched Controls J. Clin. Oncol., September 20, 2005; 23(27): 6596 - 6606. [Abstract] [Full Text] [PDF]

				K. K. Ness, S. Bhatia, K. S. Baker, L. Francisco, A. Carter, S. J. Forman, L. L. Robison, J. Rosenthal, and J. G. Gurney Performance Limitations and Participation Restrictions Among Childhood Cancer Survivors Treated With Hematopoietic Stem Cell Transplantation: The Bone Marrow Transplant Survivor Study Arch Pediatr Adolesc Med, August 1, 2005; 159(8): 706 - 713. [Abstract] [Full Text] [PDF]

				A. Tefferi, G. W. Dewald, M. L. Litzow, J. Cortes, M. J. Mauro, M. Talpaz, and H. M. Kantarjian Chronic Myeloid Leukemia: Current Application of Cytogenetics and Molecular Testing for Diagnosis and Treatment Mayo Clin. Proc., March 1, 2005; 80(3): 390 - 402. [Abstract] [PDF]

				M. A. Andrykowski, M. M. Bishop, E. A. Hahn, D. F. Cella, J. L. Beaumont, M. J. Brady, M. M. Horowitz, K. A. Sobocinski, J. D. Rizzo, and J. R. Wingard Long-Term Health-Related Quality of Life, Growth, and Spiritual Well-Being After Hematopoietic Stem-Cell Transplantation J. Clin. Oncol., January 20, 2005; 23(3): 599 - 608. [Abstract] [Full Text] [PDF]

				S. J. Lee, S. Joffe, H. T. Kim, G. Socie, A. L. Gilman, J. R. Wingard, M. M. Horowitz, D. Cella, and K. L. Syrjala Physicians' attitudes about quality-of-life issues in hematopoietic stem cell transplantation Blood, October 1, 2004; 104(7): 2194 - 2200. [Abstract] [Full Text] [PDF]

				K. S. Baker, J. G. Gurney, K. K. Ness, R. Bhatia, S. J. Forman, L. Francisco, P. B. McGlave, L. L. Robison, D. S. Snyder, D. J. Weisdorf, et al. Late effects in survivors of chronic myeloid leukemia treated with hematopoietic cell transplantation: results from the Bone Marrow Transplant Survivor Study Blood, September 15, 2004; 104(6): 1898 - 1906. [Abstract] [Full Text] [PDF]

				E. A. Hahn, G. A. Glendenning, M. V. Sorensen, S. A. Hudgens, B. J. Druker, F. Guilhot, R. A. Larson, S. G. O'Brien, D. G. Dobrez, M. L. Hensley, et al. Quality of Life in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia on Imatinib Versus Interferon Alfa Plus Low-Dose Cytarabine: Results From the IRIS Study J. Clin. Oncol., June 1, 2003; 21(11): 2138 - 2146. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kiss, T.L. Articles by Messner, H.A. Search for Related Content PubMed PubMed Citation Articles by Kiss, T.L. Articles by Messner, H.A. Social Bookmarking                            What's this?