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1. Exploring Stem Cell Transplanted Patients’ Perspectives on Medication Self-Management and Electronic Monitoring Devices Measuring Medication Adherence: A Qualitative Sub-Study of the Swiss SMILe Implementation Science Project

Author

Ribaut J, De Geest S, Leppla L, Gerull S, Teynor A, and Valenta S

Subjects
allogeneic hematopoietic stem cell transplantation, medication adherence, electronic monitor-ing, patient empowerment, focus groups, Medicine (General), R5-920
Abstract

Janette Ribaut,1,2 Sabina De Geest,1,3 Lynn Leppla,1,4 Sabine Gerull,2,5 Alexandra Teynor,6 Sabine Valenta1,2 On behalf of the SMILe study team1Institute of Nursing Science, Department Public Health, Faculty of Medicine, University of Basel, Basel, Switzerland; 2Department of Theragnostic, Hematology, University Hospital of Basel, Basel, Switzerland; 3Academic Center for Nursing and Midwifery, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; 4Departments of Hematology, Oncology and Stem Cell Transplantation, Medical Center University of Freiburg, Freiburg, Germany; 5Department of Hematology, Cantonal Hospital of Aarau, Aarau, Switzerland; 6Department of Computer Science, University of Applied Sciences, Augsburg, GermanyCorrespondence: Sabine ValentaInstitute of Nursing Science, Department Public Health, Faculty of Medicine, University of Basel, Bernoullistrasse 28, Basel, CH-4056, SwitzerlandTel +41 61 32 85275Email sabine.valenta@unibas.chPurpose: Little is known about allogeneic stem cell transplant (alloSCT) patients’ medication adherence strategies. Acceptability and preferences regarding electronic monitoring (EM) systems to assess all three phases of medication adherence (ie, initiation, implementation, persistence) are crucial to allow their successful implementation in clinical or research settings but have not yet been evaluated. We therefore aimed to explore: 1) alloSCT patients’ medication adherence and self-management strategies; and 2) their acceptability and preferences of three different EM systems (MEMS Cap, Helping Hand, Button) as part of the Swiss SMILe study.Patients and Methods: Respecting anti-pandemic measures, we used a purposive sample of six adult alloSCT patients from the University Hospital Basel, Switzerland (USB)— 6 weeks to 2 years post-alloSCT—to conduct three focus group sessions with two patients each. Using a semi-structured outline, we explored 1) patients’ medication adherence strategies and medication self-management; and 2) their acceptance and preferences regarding EM use. The three tested EM systems were available for testing during each session. Discussions were audio-recorded, visualized using mind-mapping and analyzed using Mayring’s qualitative content analysis.Results: Patients (33% females; mean age 54.6± 16.3 years; 10.4± 8.4 months post-alloSCT) used medication adherence enhancing strategies (eg, preparing pillbox, linking intake to a habit). Still, they indicated that post-alloSCT medication management was challenging (eg, frequent schedule changes). All participants preferred the MEMS Button. Participants said its small size and the possibility to combine it with existing pillboxes (eg, putting it into/next to them) made them more confident about implementing it in their daily lives.Conclusion: Regarding EM systems for medication adherence, end-user preferences and acceptability influence adoption and fidelity. Of the three systems tested, our sample found the MEMS Button most acceptable and most preferable. Therefore, we will use it for our USB SMILe study.Keywords: allogeneic hematopoietic stem cell transplantation, medication adherence, electronic monitoring, patient empowerment, focus groups

Published
2022

2. Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes.

Author

Ulrickson, M, Verdonck, L, Wirk, B, Wood, W, Yared, J, Saber, W, Tay, J, Beattie, S, Bredeson, C, Brazauskas, R, He, N, Ahmed, I, Aljurf, M, Askar, M, Atsuta, Y, Badawy, S, Barata, A, Beitinjaneh, A, Bhatt, N, Buchbinder, D, Cerny, J, Ciurea, S, DSouza, A, Dalal, J, Farhadfar, N, Freytes, C, Ganguly, S, Gergis, U, Gerull, S, Lazarus, H, Hahn, T, Hong, S, Inamoto, Y, Khera, N, Kindwall-Keller, T, Kamble, R, Knight, J, Koleva, Y, Kumar, A, Kwok, J, Murthy, H, Olsson, R, Angel Diaz-Perez, M, Rizzieri, D, Seo, S, Chhabra, S, Schoemans, H, Schouten, H, Steinberg, A, Sullivan, K, Szer, J, and Szwajcer, D

Subjects
Hematopoietic cell transplantation, graft-versus-host disease, marital status, overall survival, registries, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Marital Status, Quality of Life
Abstract

BACKGROUND: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. METHODS: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. RESULTS: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). CONCLUSIONS: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Published
2020

6. Context-specific adaption, implementation and evaluation of an eHealth-facilitated integrated care model in allogeneic stem cell transplantation - the Swiss SMILe project

Author

Valenta, S, Ribaut, J, Leppla, L, Teynor, A, Gerull, S, Mielke, J, Koehly, K, Grossmann, F, Simon, M, Bartakova, J, Kaier, K, Eckstein, J, and De Geest, S

Subjects
Science & Technology, Medicine, General & Internal, General & Internal Medicine, Life Sciences & Biomedicine
Abstract

ispartof: pages:18S-18S ispartof: SWISS MEDICAL WEEKLY vol:152 pages:18S-18S status: published

Published
2022

14. Synergistic effect of sorafenib and cGvHD in patients with high-risk FLT3-ITD+AML allows long-term disease control after allogeneic transplantation

Author

Tschan-Plessl, A., Halter, J., Heim, D., Medinger, M., Passweg, J., Gerull, S., Tschan-Plessl, A., Halter, J., Heim, D., Medinger, M., Passweg, J., and Gerull, S.

Abstract

The multikinase inhibitor sorafenib has shown a strong anti-leukemic effect in FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML); however, remission is often transient. To better understand the role of sorafenib, we performed a retrospective analysis of all patients who received sorafenib in combination with allogeneic hematopoietic stem cell transplantation (HSCT) at our center. Seventeen patients with FLT3-ITD positive AML were treated with sorafenib in combination with allogeneic HSCT. Seven patients received sorafenib therapy pre- and posttransplant, and 10 patients were given sorafenib only posttransplant. Median duration of sorafenib treatment was 13months (range 1-42); median dose was 600mg (range 100-1200). Fourteen patients (82%) achieved a complete remission (CR), while 5 patients (29%) eventually developed progressive disease. Developing chronic graft-versus-host disease (GvHD) had a strong protective influence on the risk of sorafenib resistance (p = 0.028, HR 0.08, 95% CI 0.01-0.76). In a total of 8 patients, sorafenib had to be stopped, paused or dose-reduced due to toxicity. In 5 patients with pronounced toxicity, we switched to an alternating dosing schedule with 1month on/1month off sorafenib. These patients subsequently remained in sustained complete molecular remission, with a median follow-up of 20months. Our data indicate that sorafenib can achieve high rates of sustained remission in high-risk patients treated in combination with HSCT.

Published
2021

21. Pre-transplant marital status and hematopoietic cell transplantation outcomes

Author

Tay, J., Beattie, S., Bredeson, C., Brazauskas, R., He, N., Ahmed, I. A., Aljurf, M., Askar, M., Atsuta, Y., Badawy, S., Barata, A., Beitinjaneh, A. M., Bhatt, N. S., Buchbinder, D., Cerny, J., Ciurea, S., D'Souza, A., Dalal, J., Farhadfar, N., Freytes, C. O., Ganguly, S., Gergis, U., Gerull, S., Lazarus, H. M., Hahn, T., Hong, S., Inamoto, Y., Khera, N., Kindwall-Keller, T., Kamble, R. T., Knight, J. M., Koleva, Y. N., Kumar, A., Kwok, J., Murthy, H. S., Olsson, R. F., Angel Diaz-Perez, M., Rizzieri, D., Seo, S., Chhabra, S., Schoemans, H., Schouten, H. C., Steinberg, A., Sullivan, K. M., Szer, J., Szwajcer, D., Ulrickson, M. L., Verdonck, L. F., Wirk, B., Wood, W. A., Yared, J. A., Saber, W., Tay, J., Beattie, S., Bredeson, C., Brazauskas, R., He, N., Ahmed, I. A., Aljurf, M., Askar, M., Atsuta, Y., Badawy, S., Barata, A., Beitinjaneh, A. M., Bhatt, N. S., Buchbinder, D., Cerny, J., Ciurea, S., D'Souza, A., Dalal, J., Farhadfar, N., Freytes, C. O., Ganguly, S., Gergis, U., Gerull, S., Lazarus, H. M., Hahn, T., Hong, S., Inamoto, Y., Khera, N., Kindwall-Keller, T., Kamble, R. T., Knight, J. M., Koleva, Y. N., Kumar, A., Kwok, J., Murthy, H. S., Olsson, R. F., Angel Diaz-Perez, M., Rizzieri, D., Seo, S., Chhabra, S., Schoemans, H., Schouten, H. C., Steinberg, A., Sullivan, K. M., Szer, J., Szwajcer, D., Ulrickson, M. L., Verdonck, L. F., Wirk, B., Wood, W. A., Yared, J. A., and Saber, W.

Abstract

Background Evidence about the impact of marital status before hematopoietic cell transplantation (HCT) on outcomes after HCT is conflicting. Methods We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent HCT between January 2008 and December 2015. Marital status before HCT was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after HCT. Results We identified 10,226 allogeneic and 5714 autologous HCT cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (GVHD), p < 0.001, and chronic GVHD, p = 0.04. The risk of grades 2-4 acute GVHD was increased in separated compared with married patients [hazard ratio (FIR): 1.13; 95% confidence interval (CI): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute GVHD (FIR: 0.87; 95% CI: 0.77 to 0.98). The risk of chronic GVHD was lower in widowed compared with married patients (FIR: 0.82; 95% CI: 0.67 to 0.99). Conclusions Overall survival after HCT is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic GVHD. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Published
2020
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22. Pre-transplant marital status and hematopoietic cell transplantation outcomes

Author

Tay, J, Beattie, S, Bredeson, C, Brazauskas, R, He, N, Ahmed, IA, Aljurf, M, Askar, M, Atsuta, Y, Badawy, S, Barata, A, Beitinjaneh, AM, Bhatt, NS, Buchbinder, D, Cerny, J, Ciurea, S, D'Souza, A, Dalal, J, Farhadfar, N, Freytes, CO, Ganguly, S, Gergis, U, Gerull, S, Lazarus, HM, Hahn, T, Hong, S, Inamoto, Y, Khera, N, Kindwall-Keller, T, Kamble, RT, Knight, JM, Koleva, YN, Kumar, A, Kwok, J, Murthy, HS, Olsson, RF, Angel Diaz-Perez, M, Rizzieri, D, Seo, S, Chhabra, S, Schoemans, H, Schouten, HC, Steinberg, A, Sullivan, KM, Szer, J, Szwajcer, D, Ulrickson, ML, Verdonck, LF, Wirk, B, Wood, WA, Yared, JA, Saber, W, Tay, J, Beattie, S, Bredeson, C, Brazauskas, R, He, N, Ahmed, IA, Aljurf, M, Askar, M, Atsuta, Y, Badawy, S, Barata, A, Beitinjaneh, AM, Bhatt, NS, Buchbinder, D, Cerny, J, Ciurea, S, D'Souza, A, Dalal, J, Farhadfar, N, Freytes, CO, Ganguly, S, Gergis, U, Gerull, S, Lazarus, HM, Hahn, T, Hong, S, Inamoto, Y, Khera, N, Kindwall-Keller, T, Kamble, RT, Knight, JM, Koleva, YN, Kumar, A, Kwok, J, Murthy, HS, Olsson, RF, Angel Diaz-Perez, M, Rizzieri, D, Seo, S, Chhabra, S, Schoemans, H, Schouten, HC, Steinberg, A, Sullivan, KM, Szer, J, Szwajcer, D, Ulrickson, ML, Verdonck, LF, Wirk, B, Wood, WA, Yared, JA, and Saber, W

Abstract

BACKGROUND: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. METHODS: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. RESULTS: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). CONCLUSIONS: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Published
2020

25. Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Author

Tay, J., primary, Beattie, S., additional, Bredeson, C., additional, Brazauskas, R., additional, He, N., additional, Ahmed, I. A., additional, Aljurf, M., additional, Askar, M., additional, Atsuta, Y., additional, Badawy, S., additional, Barata, A., additional, Beitinjaneh, A. M., additional, Bhatt, N. S., additional, Buchbinder, D., additional, Cerny, J., additional, Ciurea, S., additional, D’Souza, A., additional, Dalal, J., additional, Farhadfar, N., additional, Freytes, C. O., additional, Ganguly, S., additional, Gergis, U., additional, Gerull, S., additional, Lazarus, H. M., additional, Hahn, T., additional, Hong, S., additional, Inamoto, Y., additional, Khera, N., additional, Kindwall-Keller, T., additional, Kamble, R. T., additional, Knight, J. M., additional, Koleva, Y. N., additional, Kumar, A., additional, Kwok, J., additional, Murthy, H. S., additional, Olsson, R. F., additional, Angel Diaz-Perez, M., additional, Rizzieri, D., additional, Seo, S., additional, Chhabra, S., additional, Schoemans, H., additional, Schouten, H. C., additional, Steinberg, A., additional, Sullivan, K. M., additional, Szer, J., additional, Szwajcer, D., additional, Ulrickson, M. L., additional, Verdonck, L. F., additional, Wirk, B., additional, Wood, W. A., additional, Yared, J. A., additional, and Saber, W., additional

Published
2020
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30. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells

Author

Mathew, N.R., Baumgartner, F., Braun, L., O'Sullivan, D., Thomas, S., Waterhouse, M., Muller, T.A., Hanke, K., Taromi, S., Apostolova, P., Illert, A.L., Melchinger, W., Duquesne, S., Schmitt-Graeff, A., Osswald, L., Yan, K.L., Weber, A, Tugues, S., Spath, S., Pfeifer, D., Follo, M., Claus, R., Lubbert, M., Rummelt, C., Bertz, H., Wasch, R., Haag, J., Schmidts, A., Schultheiss, M., Bettinger, D., Thimme, R., Ullrich, E., Tanriver, Y., Vuong, G.L., Arnold, R., Hemmati, P., Wolf, D., Ditschkowski, M., Jilg, C., Wilhelm, K., Leiber, C., Gerull, S., Halter, J., Lengerke, C., Pabst, T., Schroeder, T., Kobbe, G., Rosler, W., Doostkam, S., Meckel, S., Stabla, K., Metzelder, S.K., Halbach, S., Brummer, T., Hu, Z, Dengjel, J., Hackanson, B., Schmid, C., Holtick, U., Scheid, C., Spyridonidis, A., Stolzel, F., Ordemann, R., Muller, L.P., Sicre-de-Fontbrune, F., Ihorst, G., Kuball, J., Ehlert, J.E., Feger, D., Wagner, E.M., Cahn, J.Y., Schnell, J., Kuchenbauer, F., Bunjes, D., Chakraverty, R., Richardson, S., Gill, S., Kroger, N., Ayuk, F., Vago, L., Ciceri, F., Muller, A.M., Kondo, T., Teshima, T., Klaeger, S., Kuster, B., Kim, D.D.H., Weisdorf, D., Velden, W.J. van der, Dorfel, D., Bethge, W., Hilgendorf, I., Hochhaus, A., Andrieux, G., Borries, M., Busch, H., Magenau, J., Reddy, P., Labopin, M., Antin, J.H., et al., Mathew, N.R., Baumgartner, F., Braun, L., O'Sullivan, D., Thomas, S., Waterhouse, M., Muller, T.A., Hanke, K., Taromi, S., Apostolova, P., Illert, A.L., Melchinger, W., Duquesne, S., Schmitt-Graeff, A., Osswald, L., Yan, K.L., Weber, A, Tugues, S., Spath, S., Pfeifer, D., Follo, M., Claus, R., Lubbert, M., Rummelt, C., Bertz, H., Wasch, R., Haag, J., Schmidts, A., Schultheiss, M., Bettinger, D., Thimme, R., Ullrich, E., Tanriver, Y., Vuong, G.L., Arnold, R., Hemmati, P., Wolf, D., Ditschkowski, M., Jilg, C., Wilhelm, K., Leiber, C., Gerull, S., Halter, J., Lengerke, C., Pabst, T., Schroeder, T., Kobbe, G., Rosler, W., Doostkam, S., Meckel, S., Stabla, K., Metzelder, S.K., Halbach, S., Brummer, T., Hu, Z, Dengjel, J., Hackanson, B., Schmid, C., Holtick, U., Scheid, C., Spyridonidis, A., Stolzel, F., Ordemann, R., Muller, L.P., Sicre-de-Fontbrune, F., Ihorst, G., Kuball, J., Ehlert, J.E., Feger, D., Wagner, E.M., Cahn, J.Y., Schnell, J., Kuchenbauer, F., Bunjes, D., Chakraverty, R., Richardson, S., Gill, S., Kroger, N., Ayuk, F., Vago, L., Ciceri, F., Muller, A.M., Kondo, T., Teshima, T., Klaeger, S., Kuster, B., Kim, D.D.H., Weisdorf, D., Velden, W.J. van der, Dorfel, D., Bethge, W., Hilgendorf, I., Hochhaus, A., Andrieux, G., Borries, M., Busch, H., Magenau, J., Reddy, P., Labopin, M., and Antin, J.H., et al.

Abstract

Contains fulltext : 190745.pdf (publisher's version ) (Closed access), Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD(+) leukemia cells. This synergized with the allogeneic CD8(+) T cell response, leading to long-term survival in six mouse models of FLT3-ITD(+) AML. Sorafenib-related IL-15 production caused an increase in CD8(+)CD107a(+)IFN-gamma(+) T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD(+) AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8(+) T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.

Published
2018

34. Forty years of haematopoietic stem cell transplantation: a review of the Basel experience

Author

O'Meara, A, primary, Holbro, A, additional, Meyer, S, additional, Martinez, M, additional, Medinger, M, additional, Buser, A, additional, Halter, J, additional, Heim, D, additional, Gerull, S, additional, Bucher, C, additional, Rovo, A, additional, Kuehne, T, additional, Tichelli, A, additional, Gratwohl, A, additional, Stern, M, additional, and Passweg, J, additional

Published
2014
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35. Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation

Author

Gerull, S., primary, Stern, M., additional, Apperley, J., additional, Beelen, D., additional, Brinch, L., additional, Bunjes, D., additional, Butler, A., additional, Ganser, A., additional, Ghavamzadeh, A., additional, Koh, M. B., additional, Komarnicki, M., additional, Kroger, N., additional, Maertens, J., additional, Maschan, A., additional, Peters, C., additional, Rovira, M., additional, Sengelov, H., additional, Socie, G., additional, Tischer, J., additional, Oneto, R., additional, Passweg, J., additional, and Marsh, J., additional

Published
2013
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47. Synergistic effect of sorafenib and cGvHD in patients with high-risk FLT3-ITD+AML allows long-term disease control after allogeneic transplantation

Author

Tschan-Plessl, A., Halter, J., Heim, D., Medinger, M., Passweg, J., Gerull, S., Tschan-Plessl, A., Halter, J., Heim, D., Medinger, M., Passweg, J., and Gerull, S.

Abstract

The multikinase inhibitor sorafenib has shown a strong anti-leukemic effect in FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML); however, remission is often transient. To better understand the role of sorafenib, we performed a retrospective analysis of all patients who received sorafenib in combination with allogeneic hematopoietic stem cell transplantation (HSCT) at our center. Seventeen patients with FLT3-ITD positive AML were treated with sorafenib in combination with allogeneic HSCT. Seven patients received sorafenib therapy pre- and posttransplant, and 10 patients were given sorafenib only posttransplant. Median duration of sorafenib treatment was 13months (range 1-42); median dose was 600mg (range 100-1200). Fourteen patients (82%) achieved a complete remission (CR), while 5 patients (29%) eventually developed progressive disease. Developing chronic graft-versus-host disease (GvHD) had a strong protective influence on the risk of sorafenib resistance (p = 0.028, HR 0.08, 95% CI 0.01-0.76). In a total of 8 patients, sorafenib had to be stopped, paused or dose-reduced due to toxicity. In 5 patients with pronounced toxicity, we switched to an alternating dosing schedule with 1month on/1month off sorafenib. These patients subsequently remained in sustained complete molecular remission, with a median follow-up of 20months. Our data indicate that sorafenib can achieve high rates of sustained remission in high-risk patients treated in combination with HSCT.

48. Prognostic impact of iron parameters in patients undergoing allo-SCT.

Author

Bazuaye, G N, Buser, A, Gerull, S, Tichelli, A, and Stern, M

Subjects
PUBLISHED errata, NAMES, SPELLING errors
Abstract

A correction to the article "Prognostic impact of iron parameters in patients undergoing allo-SCT" that was published in the 2012 issue is presented, which discusses the misspelling of the name of G. N. Bazuaye.

Published
2012
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49. Late relapse after stopping sorafenib in allogeneic hematopoietic stem cell transplant recipients

Author

Jakob Passweg, Jörg Halter, R Mathew, Gayathri Nair, Astrid Tschan-Plessl, Sabine Gerull, University of Zurich, and Gerull, S

Subjects
Sorafenib, Oncology, medicine.medical_specialty, Myeloid, 2747 Transplantation, medicine.medical_treatment, 2720 Hematology, 610 Medicine & health, Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Transplantation, business.industry, Hematology, medicine.disease, Leukemia, medicine.anatomical_structure, 030220 oncology & carcinogenesis, 10032 Clinic for Oncology and Hematology, Allogeneic hematopoietic stem cell transplant, business, Late Relapse, 030215 immunology, medicine.drug
Published
2019

50. Allo-SCT for multiple myeloma in the era of novel agents: a retrospective study on behalf of Swiss Blood SCT

Author

Martin Stern, Georg Stussi, Sabine Gerull, Jacob Passweg, A Ben Aissa, Urs Schanz, Markus G. Manz, Bilal Mohty, Yves Chalandon, University of Zurich, and Gerull, S

Subjects
Adult, Oncology, medicine.medical_specialty, 2747 Transplantation, 2720 Hematology, 610 Medicine & health, Cohort Studies, Young Adult, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Transplantation, Homologous, Multiple myeloma, Aged, Retrospective Studies, Transplantation, business.industry, Retrospective cohort study, Hematology, Allo sct, Middle Aged, medicine.disease, humanities, Treatment Outcome, surgical procedures, operative, Novel agents, Immunology, 10032 Clinic for Oncology and Hematology, Multiple Myeloma, business, human activities, Stem Cell Transplantation
Abstract

Despite the introduction of novel drugs, cure of multiple myeloma remains rare. Allo-SCT can induce long-term remission, but randomized studies in advanced disease are lacking and the influence of novel drugs remains unclear. In our retrospective analysis of all patients with myeloma allografted in Switzerland, 95 patients were transplanted between 1988 and 2011. Most patients were heavily pre-treated, and 53% received novel drugs before transplant. In all, 51% were allografted after relapse or progression. Transplant trends changed over time with an increase in reduced intensity conditioning and unrelated donors. At the time of analysis 47 patients remained alive, with a median follow-up of survivors of 53 months. Acute GVHD II-IV and chronic GVHD (cGVHD) occurred in 49% and 53%, respectively; TRM at 5 years was 18%. Five-year OS and PFS were 51% and 29%, respectively. Patients who received transplant upfront vs after relapse had a significantly better outcome, as well as those who had a related donor and achieved CR post transplant. We found no impact of pre-treatment with novel drugs or cGVHD. Although long-term remission following allo-SCT can be achieved, GVHD and TRM remain major limitations. Our series suggests that benefit is highest when allo-SCT is used early in the disease.

Published
2013

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