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Published in: Journal of Cancer Research and Clinical Oncology 11/2019

01-11-2019 | Chronic Lymphocytic Leukemia | Original Article – Clinical Oncology

Reduced intensity conditioning regimens including alkylating chemotherapy do not alter survival outcomes after allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia compared to low-intensity non-myeloablative conditioning

Authors: Niels Smedegaard Andersen, Martin Bornhäuser, Martin Gramatzki, Peter Dreger, Antonin Vitek, Michal Karas, Mauricette Michallet, Carol Moreno, Michel van Gelder, Anja Henseler, Liesbeth C. de Wreede, Stefan Schönland, Nicolaus Kröger, Johannes Schetelig, the CLL subcommittee, Chronic Malignancies Working Party

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2019

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Abstract

Purpose

The optimal dose intensity for conditioning prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) for chronic lymphocytic leukemia (CLL) is unknown.

Methods

We retrospectively compared outcomes of patients who received a first alloHCST after non-myeloablative (NMA) and reduced intensity conditioning (RIC). Data of 432 patients with a median age of 55 years were included, of which 86 patients underwent NMA and 346 RIC.

Results

The median follow-up after alloHSCT was 4.3 years. Compared to the RIC group, more NMA patients had purine-analog-sensitive disease, were in complete remission and received matched related donor transplantation. After RIC, the probabilities for 5-year OS, EFS, CIR, and NRM were 46%, 38%, 28%, and 35% and after NMA the respective probabilities were 52%, 43%, 25%, and 32%. In multivariate analysis, remission status prior to conditioning but not RIC versus NMA conditioning had a significant impact on CIR, EFS, and OS.

Conclusion

Presumed higher anti-leukemic activity of RIC versus NMA conditioning did not translate into better outcomes after alloHSCT, but better remission status prior to conditioning did. Effective pathway inhibitor-based salvage therapies combined with NMA conditioning might thus represent the most attractive contemporary approach for alloHSCT for patients with CLL.
Literature
go back to reference Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, Barrett J, Blaise D, Lowski R, Horowitz M (2009) Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transpl 15:1628–1633CrossRef Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, Barrett J, Blaise D, Lowski R, Horowitz M (2009) Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transpl 15:1628–1633CrossRef
go back to reference Brown JR, Kim HT, Armand P, Cutler C, Fisher DC, Ho V, Koreth J, Ritz J, Wu C, Antin JH, Soiffer RJ, Gribben JG, Alyea EP (2013) Long-term follow-up of reduced-intensity allogeneic stem cell transplantation for chronic lymphocytic leukemia: prognostic model to predict outcome. Leukemia 27:362–369CrossRefPubMed Brown JR, Kim HT, Armand P, Cutler C, Fisher DC, Ho V, Koreth J, Ritz J, Wu C, Antin JH, Soiffer RJ, Gribben JG, Alyea EP (2013) Long-term follow-up of reduced-intensity allogeneic stem cell transplantation for chronic lymphocytic leukemia: prognostic model to predict outcome. Leukemia 27:362–369CrossRefPubMed
go back to reference Cwynarski K, van Biezen A, de Wreede L, Stilgenbauer S, Bunjes D, Metzner B, Koza V, Mohty M, Remes K, Russell N, Nagler A, Scholten M, de Witte T, Sureda A, Dreger P (2012) Autologous and allogeneic stem-cell transplantation for transformed chronic lymphocytic leukemia (Richter’s syndrome): a retrospective analysis from the chronic lymphocytic leukemia subcommittee of the chronic leukemia working party and lymphoma working party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 30:2211–2217CrossRefPubMed Cwynarski K, van Biezen A, de Wreede L, Stilgenbauer S, Bunjes D, Metzner B, Koza V, Mohty M, Remes K, Russell N, Nagler A, Scholten M, de Witte T, Sureda A, Dreger P (2012) Autologous and allogeneic stem-cell transplantation for transformed chronic lymphocytic leukemia (Richter’s syndrome): a retrospective analysis from the chronic lymphocytic leukemia subcommittee of the chronic leukemia working party and lymphoma working party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 30:2211–2217CrossRefPubMed
go back to reference Davids MS (2017) How should we sequence and combine novel therapies in CLL? Hematol Am Soc Hematol Educ Progr 2017:346–353CrossRef Davids MS (2017) How should we sequence and combine novel therapies in CLL? Hematol Am Soc Hematol Educ Progr 2017:346–353CrossRef
go back to reference Delgado J, Pillai S, Benjamin R, Caballero D, Martino R, Nathwani A, Lovell R, Thomson K, Perez-Simon JA, Sureda A, Kottaridis P, Vazquez L, Peggs K, Sierra J, Milligan D, Mackinnon S (2008) The effect of in vivo T cell depletion with alemtuzumab on reduced-intensity allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia. Biol Blood Marrow Transpl 14:1288–1297CrossRef Delgado J, Pillai S, Benjamin R, Caballero D, Martino R, Nathwani A, Lovell R, Thomson K, Perez-Simon JA, Sureda A, Kottaridis P, Vazquez L, Peggs K, Sierra J, Milligan D, Mackinnon S (2008) The effect of in vivo T cell depletion with alemtuzumab on reduced-intensity allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia. Biol Blood Marrow Transpl 14:1288–1297CrossRef
go back to reference Dighiero G, Travade P, Chevret S, Fenaux P, Chastang C, Binet JL (1991) B-cell chronic lymphocytic leukemia: present status and future directions. French Cooper Group CLL Blood 78:1901–1914 Dighiero G, Travade P, Chevret S, Fenaux P, Chastang C, Binet JL (1991) B-cell chronic lymphocytic leukemia: present status and future directions. French Cooper Group CLL Blood 78:1901–1914
go back to reference Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L, Dohner K, Bentz M, Lichter P (2000) Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343:1910–1916CrossRefPubMed Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L, Dohner K, Bentz M, Lichter P (2000) Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343:1910–1916CrossRefPubMed
go back to reference Dreger P, Brand R, Milligan D, Corradini P, Finke J, Lambertenghi Deliliers G, Martino R, Russell N, van Biezen A, Michallet M, Niederwieser D (2005) Reduced-intensity conditioning lowers treatment-related mortality of allogeneic stem cell transplantation for chronic lymphocytic leukemia: a population-matched analysis. Leukemia 19:1029–1033CrossRefPubMed Dreger P, Brand R, Milligan D, Corradini P, Finke J, Lambertenghi Deliliers G, Martino R, Russell N, van Biezen A, Michallet M, Niederwieser D (2005) Reduced-intensity conditioning lowers treatment-related mortality of allogeneic stem cell transplantation for chronic lymphocytic leukemia: a population-matched analysis. Leukemia 19:1029–1033CrossRefPubMed
go back to reference Dreger P, Corradini P, Kimby E, Michallet M, Milligan D, Schetelig J, Wiktor-Jedrzejczak W, Niederwieser D, Hallek M, Montserrat E (2007) Chronic Leukemia Working Party of the E. Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus Leukemia 21:12–17PubMed Dreger P, Corradini P, Kimby E, Michallet M, Milligan D, Schetelig J, Wiktor-Jedrzejczak W, Niederwieser D, Hallek M, Montserrat E (2007) Chronic Leukemia Working Party of the E. Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus Leukemia 21:12–17PubMed
go back to reference Dreger P, Ghia P, Schetelig J, van Gelder M, Kimby E, Michallet M, Moreno C, Robak T, Stilgenbauer S, Montserrat E (2018a) High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies. Blood 132:892–902CrossRefPubMed Dreger P, Ghia P, Schetelig J, van Gelder M, Kimby E, Michallet M, Moreno C, Robak T, Stilgenbauer S, Montserrat E (2018a) High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies. Blood 132:892–902CrossRefPubMed
go back to reference Dreger P, Michallet M, Bosman P, Dietrich S, Sobh M, Boumendil A, Nagler A, Scheid C, Cornelissen J, Niederwieser D, Muller L, Vandenberghe E, Scortechini I, Schoemans H, Andersen NS, Finke J, Russo D, Ljungman P, Passweg J, van Gelder M, Durakovic N, Labussiere-Wallet H, Berg T, Wulf G, Bethge W, Bunjes D, Stilgenbauer S, Canepari ME, Schaap M, Fox CP, Kroger N, Montoto S, Schetelig J (2018b) Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties. Bone Marrow Transpl 54:44CrossRef Dreger P, Michallet M, Bosman P, Dietrich S, Sobh M, Boumendil A, Nagler A, Scheid C, Cornelissen J, Niederwieser D, Muller L, Vandenberghe E, Scortechini I, Schoemans H, Andersen NS, Finke J, Russo D, Ljungman P, Passweg J, van Gelder M, Durakovic N, Labussiere-Wallet H, Berg T, Wulf G, Bethge W, Bunjes D, Stilgenbauer S, Canepari ME, Schaap M, Fox CP, Kroger N, Montoto S, Schetelig J (2018b) Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties. Bone Marrow Transpl 54:44CrossRef
go back to reference Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Gorlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N (2014) Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol 15:757–766CrossRefPubMed Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Gorlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N (2014) Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol 15:757–766CrossRefPubMed
go back to reference Gragert L, Fingerson S, Albrecht M, Maiers M, Kalaycio M, Hill BT (2014) Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations. Blood 124:2657–2665CrossRefPubMedPubMedCentral Gragert L, Fingerson S, Albrecht M, Maiers M, Kalaycio M, Hill BT (2014) Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations. Blood 124:2657–2665CrossRefPubMedPubMedCentral
go back to reference Johnson RE (1970) Total body irradiation of chronic lymphocytic leukemia: incidence and duration of remission. Cancer 25:523–530CrossRefPubMed Johnson RE (1970) Total body irradiation of chronic lymphocytic leukemia: incidence and duration of remission. Cancer 25:523–530CrossRefPubMed
go back to reference Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE (2008) Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood 111:5530–5536CrossRefPubMedPubMedCentral Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE (2008) Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood 111:5530–5536CrossRefPubMedPubMedCentral
go back to reference Kramer I, Stilgenbauer S, Dietrich S, Bottcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Dohner H, Dreger P (2017) Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial. Blood 130:1477–1480CrossRefPubMed Kramer I, Stilgenbauer S, Dietrich S, Bottcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Dohner H, Dreger P (2017) Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial. Blood 130:1477–1480CrossRefPubMed
go back to reference Mato AR, Nabhan C, Barr PM, Ujjani CS, Hill BT, Lamanna N, Skarbnik AP, Howlett C, Pu JJ, Sehgal AR, Strelec LE, Vandegrift A, Fitzpatrick DM, Zent CS, Feldman T, Goy A, Claxton DF, Bachow SH, Kaur G, Svoboda J, Nasta SD, Porter D, Landsburg DJ, Schuster SJ, Cheson BD, Kiselev P, Evens AM (2016) Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience. Blood 128:2199–2205CrossRefPubMed Mato AR, Nabhan C, Barr PM, Ujjani CS, Hill BT, Lamanna N, Skarbnik AP, Howlett C, Pu JJ, Sehgal AR, Strelec LE, Vandegrift A, Fitzpatrick DM, Zent CS, Feldman T, Goy A, Claxton DF, Bachow SH, Kaur G, Svoboda J, Nasta SD, Porter D, Landsburg DJ, Schuster SJ, Cheson BD, Kiselev P, Evens AM (2016) Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience. Blood 128:2199–2205CrossRefPubMed
go back to reference Michallet M, Archimbaud E, Bandini G, Rowlings PA, Deeg HJ, Gahrton G, Montserrat E, Rozman C, Gratwohl A, Gale RP (1996) HLA-identical sibling bone marrow transplantation in younger patients with chronic lymphocytic leukemia. European Group for Blood and Marrow Transplantation and the International Bone Marrow Transplant Registry. Ann Intern Med 124:311–315CrossRefPubMed Michallet M, Archimbaud E, Bandini G, Rowlings PA, Deeg HJ, Gahrton G, Montserrat E, Rozman C, Gratwohl A, Gale RP (1996) HLA-identical sibling bone marrow transplantation in younger patients with chronic lymphocytic leukemia. European Group for Blood and Marrow Transplantation and the International Bone Marrow Transplant Registry. Ann Intern Med 124:311–315CrossRefPubMed
go back to reference Michallet M, Socie G, Mohty M, Sobh M, Bay JO, Morisset S, Labussiere-Wallet H, Tabrizi R, Milpied N, Bordigoni P, El-Cheikh J, Blaise D (2013) Rituximab, fludarabine, and total body irradiation as conditioning regimen before allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukemia: long-term prospective multicenter study. Exp Hematol 41:127–133CrossRefPubMed Michallet M, Socie G, Mohty M, Sobh M, Bay JO, Morisset S, Labussiere-Wallet H, Tabrizi R, Milpied N, Bordigoni P, El-Cheikh J, Blaise D (2013) Rituximab, fludarabine, and total body irradiation as conditioning regimen before allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukemia: long-term prospective multicenter study. Exp Hematol 41:127–133CrossRefPubMed
go back to reference Ritgen M, Stilgenbauer S, Von Neuhoff N, Humpe A, Bruggemann M, Pott C, Raff T, Krober A, Bunjes D, Schlenk R, Schmitz N, Dohner H, Kneba M, Dreger P (2004) Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood 104:2600–2602CrossRefPubMed Ritgen M, Stilgenbauer S, Von Neuhoff N, Humpe A, Bruggemann M, Pott C, Raff T, Krober A, Bunjes D, Schlenk R, Schmitz N, Dohner H, Kneba M, Dreger P (2004) Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood 104:2600–2602CrossRefPubMed
go back to reference Sabloff M, Sobecks RM, Ahn KW, Zhu X, de Lima M, Brown JR, Inamoto Y, Holland HK, Aljurf MD, Laughlin MJ, Kamble RT, Hsu JW, Wirk BM, Seftel M, Lewis ID, Arora M, Alyea EP, Kalaycio ME, Cortes J, Maziarz RT, Gale RP, Saber W (2014) Does total body irradiation conditioning improve outcomes of myeloablative human leukocyte antigen-identical sibling transplantations for chronic lymphocytic leukemia? Biol Blood Marrow Transpl 20:421–424CrossRef Sabloff M, Sobecks RM, Ahn KW, Zhu X, de Lima M, Brown JR, Inamoto Y, Holland HK, Aljurf MD, Laughlin MJ, Kamble RT, Hsu JW, Wirk BM, Seftel M, Lewis ID, Arora M, Alyea EP, Kalaycio ME, Cortes J, Maziarz RT, Gale RP, Saber W (2014) Does total body irradiation conditioning improve outcomes of myeloablative human leukocyte antigen-identical sibling transplantations for chronic lymphocytic leukemia? Biol Blood Marrow Transpl 20:421–424CrossRef
go back to reference Schemper M, Smith TL (1996) A note on quantifying follow-up in studies of failure time. Control Clin Trials 17:343–346CrossRefPubMed Schemper M, Smith TL (1996) A note on quantifying follow-up in studies of failure time. Control Clin Trials 17:343–346CrossRefPubMed
go back to reference Schetelig J, Thiede C, Bornhauser M, Schwerdtfeger R, Kiehl M, Beyer J, Sayer HG, Kroger N, Hensel M, Scheffold C, Held TK, Hoffken K, Ho AD, Kienast J, Neubauer A, Zander AR, Fauser AA, Ehninger G, Siegert W (2003) Cooperative German Transplant Study G. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group. J Clin Oncol 21:2747–2753CrossRefPubMed Schetelig J, Thiede C, Bornhauser M, Schwerdtfeger R, Kiehl M, Beyer J, Sayer HG, Kroger N, Hensel M, Scheffold C, Held TK, Hoffken K, Ho AD, Kienast J, Neubauer A, Zander AR, Fauser AA, Ehninger G, Siegert W (2003) Cooperative German Transplant Study G. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group. J Clin Oncol 21:2747–2753CrossRefPubMed
go back to reference Schetelig J, Chevallier P, Van Gelder M, Hoek J, Hermine O, Chakraverty R, Browne P, Milpied N, Malagola M, Socie G, Delgado J, Deconinck E, Damaj G, Cordonnier C, Beelen DW, Nguyen S, Nikolousis E, Brecht A, Mayer J, Hunault M, Bittenbring JT, Thieblemont C, Leprêtre S, de Wreede LC, Dreger P, Kröger N (2017a) Remission status at transplantation and treatment history determine the survival chances of patients after allogeneic hematopoietic stem cell transplantation for chronic lymphocytic leukemia who had received pre-treatment with idelalisib: a report from the EBMT chronic malignancies working party. Blood 130:4576 Schetelig J, Chevallier P, Van Gelder M, Hoek J, Hermine O, Chakraverty R, Browne P, Milpied N, Malagola M, Socie G, Delgado J, Deconinck E, Damaj G, Cordonnier C, Beelen DW, Nguyen S, Nikolousis E, Brecht A, Mayer J, Hunault M, Bittenbring JT, Thieblemont C, Leprêtre S, de Wreede LC, Dreger P, Kröger N (2017a) Remission status at transplantation and treatment history determine the survival chances of patients after allogeneic hematopoietic stem cell transplantation for chronic lymphocytic leukemia who had received pre-treatment with idelalisib: a report from the EBMT chronic malignancies working party. Blood 130:4576
go back to reference Schetelig J, de Wreede LC, Andersen NS, Moreno C, van Gelder M, Vitek A, Karas M, Michallet M, Machaczka M, Gramatzki M, Beelen D, Finke J, Delgado J, Volin L, Passweg J, Dreger P, Schaap N, Wagner E, Henseler A, van Biezen A, Bornhauser M, Iacobelli S, Putter H, Schonland SO, Kroger N (2017b) Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT). Br J Haematol 178:521–533CrossRefPubMed Schetelig J, de Wreede LC, Andersen NS, Moreno C, van Gelder M, Vitek A, Karas M, Michallet M, Machaczka M, Gramatzki M, Beelen D, Finke J, Delgado J, Volin L, Passweg J, Dreger P, Schaap N, Wagner E, Henseler A, van Biezen A, Bornhauser M, Iacobelli S, Putter H, Schonland SO, Kroger N (2017b) Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT). Br J Haematol 178:521–533CrossRefPubMed
go back to reference Schetelig J, de Wreede LC, van Gelder M, Andersen NS, Moreno C, Vitek A, Karas M, Michallet M, Machaczka M, Gramatzki M, Beelen D, Finke J, Delgado J, Volin L, Passweg J, Dreger P, Henseler A, van Biezen A, Bornhauser M, Schonland SO, Kroger N (2017c) Risk factors for treatment failure after allogeneic transplantation of patients with CLL: a report from the European Society for Blood and Marrow Transplantation. Bone Marrow Transpl 52:552–560CrossRef Schetelig J, de Wreede LC, van Gelder M, Andersen NS, Moreno C, Vitek A, Karas M, Michallet M, Machaczka M, Gramatzki M, Beelen D, Finke J, Delgado J, Volin L, Passweg J, Dreger P, Henseler A, van Biezen A, Bornhauser M, Schonland SO, Kroger N (2017c) Risk factors for treatment failure after allogeneic transplantation of patients with CLL: a report from the European Society for Blood and Marrow Transplantation. Bone Marrow Transpl 52:552–560CrossRef
go back to reference Schetelig J, Link CS, Stuhler G, Wagner EM, Hanel M, Kobbe G, Bottcher S, Kreuzer KA, Middeke JM, Sockel K, Teipel R, von Bonin M, Stolzel F, Kramer M, Stilgenbauer S, Hallek M, Bornhauser M (2018) Anti-CD20 immunotherapy as a bridge to tolerance, after allogeneic stem cell transplantation for patients with chronic lymphocytic leukaemia: results of the CLLX4 trial. Br J Haematol 184:833CrossRefPubMed Schetelig J, Link CS, Stuhler G, Wagner EM, Hanel M, Kobbe G, Bottcher S, Kreuzer KA, Middeke JM, Sockel K, Teipel R, von Bonin M, Stolzel F, Kramer M, Stilgenbauer S, Hallek M, Bornhauser M (2018) Anti-CD20 immunotherapy as a bridge to tolerance, after allogeneic stem cell transplantation for patients with chronic lymphocytic leukaemia: results of the CLLX4 trial. Br J Haematol 184:833CrossRefPubMed
go back to reference Shah N, Decker WK, Lapushin R, Xing D, Robinson SN, Yang H, Parmar S, Tung SS, O’Brien S, Fernandez-Vina M, Shpall EJ, Wierda WG (2011) HLA homozygosity and haplotype bias among patients with chronic lymphocytic leukemia: implications for disease control by physiological immune surveillance. Leukemia 25:1036–1039CrossRefPubMed Shah N, Decker WK, Lapushin R, Xing D, Robinson SN, Yang H, Parmar S, Tung SS, O’Brien S, Fernandez-Vina M, Shpall EJ, Wierda WG (2011) HLA homozygosity and haplotype bias among patients with chronic lymphocytic leukemia: implications for disease control by physiological immune surveillance. Leukemia 25:1036–1039CrossRefPubMed
go back to reference Sobecks RM, Leis JF, Gale RP, Ahn KW, Zhu X, Sabloff M, de Lima M, Brown JR, Inamoto Y, Hale GA, Aljurf MD, Kamble RT, Hsu JW, Pavletic SZ, Wirk B, Seftel MD, Lewis ID, Alyea EP, Cortes J, Kalaycio ME, Maziarz RT, Saber W (2014) Outcomes of human leukocyte antigen-matched sibling donor hematopoietic cell transplantation in chronic lymphocytic leukemia: myeloablative versus reduced-intensity conditioning regimens. Biol Blood Marrow Transpl 20:1390–1398CrossRef Sobecks RM, Leis JF, Gale RP, Ahn KW, Zhu X, Sabloff M, de Lima M, Brown JR, Inamoto Y, Hale GA, Aljurf MD, Kamble RT, Hsu JW, Pavletic SZ, Wirk B, Seftel MD, Lewis ID, Alyea EP, Cortes J, Kalaycio ME, Maziarz RT, Saber W (2014) Outcomes of human leukocyte antigen-matched sibling donor hematopoietic cell transplantation in chronic lymphocytic leukemia: myeloablative versus reduced-intensity conditioning regimens. Biol Blood Marrow Transpl 20:1390–1398CrossRef
go back to reference Sorror ML, Maris MB, Sandmaier BM, Storer BE, Stuart MJ, Hegenbart U, Agura E, Chauncey TR, Leis J, Pulsipher M, McSweeney P, Radich JP, Bredeson C, Bruno B, Langston A, Loken MR, Al-Ali H, Blume KG, Storb R, Maloney DG (2005) Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol 23:3819–3829CrossRefPubMed Sorror ML, Maris MB, Sandmaier BM, Storer BE, Stuart MJ, Hegenbart U, Agura E, Chauncey TR, Leis J, Pulsipher M, McSweeney P, Radich JP, Bredeson C, Bruno B, Langston A, Loken MR, Al-Ali H, Blume KG, Storb R, Maloney DG (2005) Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol 23:3819–3829CrossRefPubMed
go back to reference Sorror ML, Storer BE, Maloney DG, Sandmaier BM, Martin PJ, Storb R (2008a) Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. Blood 111:446–452CrossRefPubMedPubMedCentral Sorror ML, Storer BE, Maloney DG, Sandmaier BM, Martin PJ, Storb R (2008a) Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. Blood 111:446–452CrossRefPubMedPubMedCentral
go back to reference Sorror ML, Storer BE, Sandmaier BM, Maris M, Shizuru J, Maziarz R, Agura E, Chauncey TR, Pulsipher MA, McSweeney PA, Wade JC, Bruno B, Langston A, Radich J, Niederwieser D, Blume KG, Storb R, Maloney DG (2008b) Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol 26:4912–4920CrossRefPubMedPubMedCentral Sorror ML, Storer BE, Sandmaier BM, Maris M, Shizuru J, Maziarz R, Agura E, Chauncey TR, Pulsipher MA, McSweeney PA, Wade JC, Bruno B, Langston A, Radich J, Niederwieser D, Blume KG, Storb R, Maloney DG (2008b) Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol 26:4912–4920CrossRefPubMedPubMedCentral
go back to reference Turtle CJ, Hay KA, Hanafi LA, Li D, Cherian S, Chen X, Wood B, Lozanski A, Byrd JC, Heimfeld S, Riddell SR, Maloney DG (2017) Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib. J Clin Oncol 35:3010–3020CrossRefPubMedPubMedCentral Turtle CJ, Hay KA, Hanafi LA, Li D, Cherian S, Chen X, Wood B, Lozanski A, Byrd JC, Heimfeld S, Riddell SR, Maloney DG (2017) Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib. J Clin Oncol 35:3010–3020CrossRefPubMedPubMedCentral
go back to reference van Gelder M, de Wreede LC, Bornhauser M, Niederwieser D, Karas M, Anderson NS, Gramatzki M, Dreger P, Michallet M, Petersen E, Bunjes D, Potter M, Beelen D, Cornelissen JJ, Yakoub-Agha I, Russell NH, Finke J, Schoemans H, Vitek A, Urbano-Ispizua A, Blaise D, Volin L, Chevallier P, Caballero D, Putter H, van Biezen A, Henseler A, Schonland S, Kroger N, Schetelig J (2017) Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation. Bone Marrow Transpl 52:372–380CrossRef van Gelder M, de Wreede LC, Bornhauser M, Niederwieser D, Karas M, Anderson NS, Gramatzki M, Dreger P, Michallet M, Petersen E, Bunjes D, Potter M, Beelen D, Cornelissen JJ, Yakoub-Agha I, Russell NH, Finke J, Schoemans H, Vitek A, Urbano-Ispizua A, Blaise D, Volin L, Chevallier P, Caballero D, Putter H, van Biezen A, Henseler A, Schonland S, Kroger N, Schetelig J (2017) Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation. Bone Marrow Transpl 52:372–380CrossRef
go back to reference Weisdorf D, Spellman S, Haagenson M, Horowitz M, Lee S, Anasetti C, Setterholm M, Drexler R, Maiers M, King R, Confer D, Klein J (2008) Classification of HLA-matching for retrospective analysis of unrelated donor transplantation: revised definitions to predict survival. Biol Blood Marrow Transpl 14:748–758CrossRef Weisdorf D, Spellman S, Haagenson M, Horowitz M, Lee S, Anasetti C, Setterholm M, Drexler R, Maiers M, King R, Confer D, Klein J (2008) Classification of HLA-matching for retrospective analysis of unrelated donor transplantation: revised definitions to predict survival. Biol Blood Marrow Transpl 14:748–758CrossRef
go back to reference Zenz T, Habe S, Denzel T, Mohr J, Winkler D, Buhler A, Sarno A, Groner S, Mertens D, Busch R, Hallek M, Dohner H, Stilgenbauer S (2009) Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. Blood 114:2589–2597CrossRefPubMed Zenz T, Habe S, Denzel T, Mohr J, Winkler D, Buhler A, Sarno A, Groner S, Mertens D, Busch R, Hallek M, Dohner H, Stilgenbauer S (2009) Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. Blood 114:2589–2597CrossRefPubMed
Metadata
Title
Reduced intensity conditioning regimens including alkylating chemotherapy do not alter survival outcomes after allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia compared to low-intensity non-myeloablative conditioning
Authors
Niels Smedegaard Andersen
Martin Bornhäuser
Martin Gramatzki
Peter Dreger
Antonin Vitek
Michal Karas
Mauricette Michallet
Carol Moreno
Michel van Gelder
Anja Henseler
Liesbeth C. de Wreede
Stefan Schönland
Nicolaus Kröger
Johannes Schetelig
the CLL subcommittee, Chronic Malignancies Working Party
Publication date
01-11-2019
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 11/2019
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-019-03014-x

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