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Health-related quality of life in reduced intensity hematopoietic cell transplantation based on donor availability in patients aged 50-75 with advanced myelodysplastic syndrome: BMT CTN 1102
Cusatis, R., Martens, M. J., Nakamura, R., Cutler, C. S., Saber, W., Lee, S. J., Logan, B. R., Shaw, B. E., Gregory, A., D'Souza, A., et al
American journal of hematology. 2022
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Abstract
INTRODUCTION For myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation (alloHCT) is the only available curative therapy. The Blood and Marrow Transplant Clinical Trials Network study 1102 (BMT CTN 1102, NCT02016781) was a multicenter, biologic assignment trial based on matched donor availability in adults aged 50-75 with higher risk de novo MDS who were candidates for reduced-intensity conditioning (RIC) alloHCT. The primary analysis showed that those who received alloHCT had a survival benefit, but whether this is at the cost of worse quality of life (QOL) has not been described in detail. METHODS English and Spanish-speaking trial participants completed the Functional Assessment of Cancer Therapy - General (FACT-G), the SF-36, and the EQ-5D, at enrollment, every 6 months until 24 months, and 36 months. We compared patient-reported outcome (PRO) scores between study arms using an inverse probability weighted - independent estimating equation (IPW-IEE) model. RESULTS Between January 2014 and November 2018, 384 subjects (median age 66.7 years, range: 50.1-75.3) enrolled at 34 centers. PRO completion rates were generally high at 65-78%. The PRO trajectories for both arms were similar, with most decreasing or stable from baseline to 6 months and improving thereafter. Baseline PRO scores were the most consistent independent predictors of subsequent QOL outcomes and survival, even after controlling for clinical and patient-level factors. DISCUSSION For older adults with MDS, the survival advantage associated with Donor availability and alloHCT did not come at the cost of worse QOL. These results should reassure older patients and clinicians who prefer a curative approach to treating MDS. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Adults aged 50-75 with higher risk de novo myelodysplastic syndrome,, who were candidates for reduced-intensity conditioning and allogeneic transplant, identified in 34 centres in the USA (n=384)
Intervention
Patients with an available donor and were transplanted (n=261)
Comparison
Patients with no available donor who did not receive transplantation (n=123)
Outcome
The patient recorded outcome (PRO) trajectories for both arms were similar, with most decreasing or stable from baseline to 6 months and improving thereafter. Baseline PRO scores were the most consistent independent predictors of subsequent QOL outcomes and survival, even after controlling for clinical and patient-level factors.
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The Burden of Survivorship on Hematological Patients-Long-Term Analysis of Toxicities after Total Body Irradiation and Allogeneic Stem Cell Transplantation
Oertel, M., Martel, J., Mikesch, J. H., Scobioala, S., Reicherts, C., Kröger, K., Lenz, G., Stelljes, M., Eich, H. T.
Cancers. 2021;13(22)
Abstract
Total body irradiation is an effective conditioning modality before autologous or allogeneic stem cell transplantation. With the whole body being the radiation target volume, a diverse spectrum of toxicities has been reported. This fact prompted us to investigate the long-term sequelae of this treatment concept in a large patient cohort. Overall, 322 patients with acute leukemia or myelodysplastic syndrome with a minimum follow-up of one year were included (the median follow-up in this study was 68 months). Pulmonary, cardiac, ocular, neurological and renal toxicities were observed in 23.9%, 14.0%, 23.6%, 23.9% and 20.2% of all patients, respectively. The majority of these side effects were grades 1 and 2 (64.9-89.2% of all toxicities in the respective categories). The use of 12 Gray total body irradiation resulted in a significant increase in ocular toxicities (p = 0.013) and severe mucositis (p < 0.001). Renal toxicities were influenced by the age at transplantation (relative risk: 1.06, p < 0.001) and disease entity. In summary, total body irradiation triggers a multifaceted, but manageable, toxicity profile. Except for ocular toxicities and mucositis, a 12 Gray regimen did not lead to an increase in long-term side effects.
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Dosimetric evaluation of ovaries and pelvic bones associated with clinical outcomes in patients receiving total body irradiation with ovarian shielding
Akahane, K., Shirai, K., Wakatsuki, M., Suzuki, M., Hatanaka, S., Takahashi, Y., Kawahara, M., Ogawa, K., Takahashi, S., Oyama-Manabe, N., et al
Journal of radiation research. 2021
Abstract
Total body irradiation (TBI) with ovarian shielding is expected to preserve fertility among hematopoietic stem cell transplant (HSCT) patients with myeloablative TBI-based regimens. However, the radiation dose to the ovaries that preserves ovarian function in TBI remains poorly understood. Furthermore, it is uncertain whether the dose to the shielded organs is associated with relapse risk. Here, we retrospectively evaluated the relationship between fertility and the dose to the ovaries, and between relapse risk and the dose to the pelvic bones. A total of 20 patients (median age, 23 years) with standard-risk hematologic diseases were included. Median follow-up duration was 31.9 months. The TBI prescribed dose was 12 Gy in six fractions for three days. Patients' ovaries were shielded with cylinder-type lead blocks. The dose-volume parameters (D98% and Dmean) in the ovaries and the pelvic bones were extracted from the dose-volume histogram (DVH). The mean ovary Dmean for all patients was 2.4 Gy, and 18 patients recovered menstruation (90%). The mean ovary Dmean for patients with menstrual recovery and without recovery were 2.4 Gy and 2.4 Gy, respectively, with no significant difference (P = 0.998). Hematological relapse was observed in five patients. The mean pelvis Dmean and pelvis D98% for relapse and non-relapse patients were 11.6 Gy and 11.7 Gy and 5.6 Gy and 5.3 Gy, respectively. Both parameters showed no significant difference (P = 0.827, 0.807). In conclusion, TBI with ovarian shielding reduced the radiation dose to the ovaries to 2.4 Gy, and preserved fertility without increasing the risk of relapse.
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Ovarian insufficiency following allogeneic hematopoietic stem cell transplantation
Kawano, M., Komura, H., Kawaguchi, H., Shimizu, S., Yada-Hashimoto, N., Shimizu, M., Sato, M., Inoue, M., Ida, S., Etani, Y., et al
Gynecological Endocrinology. 2017;33(2):156-159
Abstract
Ovarian insufficiency is a serious complication for young women who undergo hematopoietic stem cell transplantation (HSCT). Reduced-intensity conditioning (RIC) has been utilized more widely due to its reduced toxicity; however, there is a lack of data concerning ovarian function after HSCT with RIC. We investigated the ovarian function in patients who received HSCT with RIC, compared to those who received myeloablative conditioning (MAC). The records of 69 female patients who received allogeneic HSCT at the institution under 40 years of age at transplantation from 1991 to 2012 were retrospectively analyzed. Prevalence of ovarian insufficiency was significantly lower in patients conditioned with RIC than in those conditioned with MAC (4/27=14.8% for RIC and 36/42=85.7% for MAC, p<0.0001). A younger age at HSCT was associated with a lower risk of ovarian insufficiency. Among the 40 patients with ovarian insufficiency, four patients recovered ovarian function, and two conceived following hormone-replacement therapy (HRT). A higher serum E2 level prior to HRT was a significant predictor for the restoration of ovarian function (p=0.0028). In conclusion, RIC was significantly less toxic to ovarian function compared with MAC. HSCT-associated ovarian insufficiency is not irreversible, and a higher E2 level may predict the restoration of ovarian function.
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Late Complications and Quality of Life after Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation
Clavert, A., Peric, Z., Brissot, E., Malard, F., Guillaume, T., Delaunay, J., Dubruille, V., Le Gouill, S., Mahe, B., Gastinne, T., et al
Biology of Blood & Marrow Transplantation. 2017;23(1):140-146
Abstract
Late complications (LC) and quality of life (QOL) were analyzed in 110 adult patients who underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) and were alive for more than 2 years after allo-SCT. Overall survival of these patients was 93% (95% confidence interval [CI], 88% to 99%) and 81% (95% CI, 71% to 94%) at 5 and 10 years, respectively. The primary cause of death was a recurrence of primary malignancy. With a median follow-up of 4.6 years (range, 2 to 12.1), chronic graft-versus-host disease (cGVHD) was the most prevalent late effect, with a cumulative incidence of 66% (95% CI, 57% to 74%) at 10 years. Cardiovascular complications were the most prevalent LC with a cumulative incidence of 47% (95% CI, 35% to 59%), followed by pulmonary complications with a cumulative incidence of 33% (95% CI, 21% to 46%) and renal impairment with a cumulative incidence of 34% (95% CI, 25% to 43%) at 10 years. Secondary malignancies occurred with a cumulative incidence of 11% (95% CI, 5% to 20%) at 10 years. In this series, 61 patients (55%) responded to QOL survey. With the use of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and Functional Assessment of Cancer Therapy-Bone Marrow Transplant questionnaires, most of the patients reported good to excellent QOL and patients with cGVHD had significantly lower QOL than patients without cGVHD. In conclusion, QOL after RIC is comparable to that seen after myeloablative conditioning, while the natural history of LC after RIC appears to be different from that described in the standard myeloablative setting, warranting further research in this field. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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Fertility in premenopausal women post autologous stem cell transplant with BEAM conditioning
Lasica, M., Taylor, E., Bhattacharyya, P., Bennett, A., Cooke, R. E., Stern, C., Agresta, F., Ayton, R., Grigg, A.
European Journal of Haematology. 2016;97(4):348-52
Abstract
There is currently minimal data on fertility outcomes in premenopausal women undergoing autologous stem cell transplant (ASCT) with carmustine, etoposide, cytarabine and melphalan (BEAM) conditioning. A retrospective analysis of fertility outcomes in premenopausal females aged between 18 and 40 yr who underwent BEAM/ASCT for lymphoma between 1995 and 2011 was performed at four transplant centres. Of 41 premenopausal women who underwent BEAM conditioning, 25 met the inclusion criteria with the main exclusion criterion being inadequate documentation. Eighteen had Hodgkin lymphoma, and seven had non-Hodgkin lymphoma. Median number of chemotherapy regimens pretransplant was 2 (1-3). Seventeen women (68%) with a median age at transplant of 25 yr (range 17-33) recovered their menses. The comparative group without recovery was older with a median age of 34 yr (range 20-40) (P = 0.007). Ten patients, with a median age at transplant of 22 yr (range 17-30), had 15 naturally conceived pregnancies. Chemotherapy regimens and lymphoma type did not obviously influence the incidence of menses recovery or conception. The incidence of recovery of menses and fertility in premenopausal women undergoing BEAM/ASCT for lymphoma is substantial. Younger age at transplant correlates with superior fertility outcomes. Copyright © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Health-Related Quality of Life in leukemia Survivors of Allogeneic Hematopoietic Stem Cell Transplantation Employing the Mexican Reduced-Intensity Conditioning
Gonzalez-Ramirez, M. P., Miravete-Lagunes, K., Gomez-de-Leon, A., Ponce-de-Leon, S., Tenorio-Rojo, A. P., Martagon-Herrera, N. A., Hernandez-Reyes, J. A., Garcia-Villasenor, A., Burguette, E., Vallejo-Villalobos, M. F., et al
Revista de Investigacion Clinica. 2015;67(2):109-16
Abstract
BACKGROUND Quality of life (QOL) is an important consideration in the counseling, implementation, and post-treatment management of arduous treatments for life-threatening conditions such as allogeneic hematopoietic cell transplantation (allo-HCT). OBJECTIVE To analyze the QOL of leukemia patients allografted with the Mexican reduced-intensity conditioning regimen in two Mexican academic medical centers. MATERIAL AND METHODS By means of the quality metric short form 36 version 2 to measure generic health concepts, relevant QOL was analyzed in leukemia patients who underwent allo-HCT using reduced-intensity conditioning on an outpatient basis at either the Centro de Hematologia y Medicina Interna de Puebla of the Clinica Ruiz or the Hematology Service of the Internal Medicine Department of the Hospital "Dr. Jose Eleuterio Gonzalez" of the Universidad Autonoma de Nuevo Leon, and who had survived more than 12 months after the allograft, who could be approached, who were in a continued complete remission (with or without graft-versus-host disease), and who were willing to respond to the questionnaire. Thirty-five patients fulfilling these requirements were included, and a sex- and age-matched group of 35 reference subjects was also studied. RESULTS Allografted patients were found to have a slightly better mental component summary than the reference subjects (53.23 vs. 48.66 points; p = 0.01), whereas the physical component summary did not show a difference (54.53 vs. 52.05 points; p = 0.59). Most of the differences between allografted individuals and reference subject controls were not significant. CONCLUSIONS Despite several sources of bias, these data suggest that allografted individuals employing the Mexican reduced-intensity conditioning regimen enjoy a health-related QOL life similar to that of reference subjects, adding another advantage of this method of conducting stem cell allografts. However, more work needs to be done to elucidate the impact of reduced-intensity conditioning on post allo-HCT QOL.