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Original Article

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Blood Res 2018; 53(2):

Published online June 25, 2018

https://doi.org/10.5045/br.2018.53.2.105

© The Korean Society of Hematology

Busulfan plus melphalan versus high-dose melphalan as conditioning regimens in autologous stem cell transplantation for newly diagnosed multiple myeloma

Ja Min Byun1,2, Jayoun Lee3, Sang-Jin Shin3, Minjoo Kang3, Sung-Soo Yoon2, and Youngil Koh2*

Author Info. +

1Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.

2Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.

3National Evidence-Based Healthcare Collaborating Agency, Seoul, Korea.

Correspondence to : Youngil Koh, M.D. Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongro-gu, Seoul 03080, Korea. go01@snu.ac.kr

Received: August 2, 2017; Revised: September 11, 2017; Accepted: October 23, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background

High-dose melphalan (HDMEL) represents the standard conditioning regimen before autologous stem cell transplant (ASCT) in multiple myeloma (MM), but recent updates have suggested combination of melphalan with bulsulfan (BUMEL) is also associated with favorable outcomes. We performed the current study to address the lack of comparative studies between the two conditioning regimens in Asian populations.

Methods

Using the Korean National Health Insurance and Korean Health Insurance Review and Assessment Service databases, 1,304 patients newly diagnosed with MM undergoing ASCT between January 2010 and December 2014 were identified. Patients were divided according to conditioning regimen (HDMEL vs. BUMEL), and after case matching, 428 patients undergoing HDMEL conditioning were compared to 107 patients undergoing BUMEL conditioning with respect to clinical course and treatment outcomes.

Results

The 3-year progression-free survival (PFS) was 52.5% for the HDMEL conditioning group versus 70.3% for the BUMEL conditioning group (P=0.043). The 3-year overall survival (OS) was 82.0% versus 83.5% (P=0.525), respectively. Although not statistically significant, BUMEL conditioning was associated with more platelet transfusion, while HDMEL was associated with more granulocyte colony stimulating factor support. In multivariate analysis, BUMEL conditioning was not inferior to HDMEL conditioning in regard to both PFS and OS.

Conclusion

Our study confirmed that BUMEL is an effective and well-tolerated alternative to HDMEL conditioning, with better PFS.

Keywords Multiple myeloma, Conditioning regimen, Autologous stem cell transplantation, Busulfan, Melphalan

Article

Original Article

Blood Res 2018; 53(2): 105-109

Published online June 25, 2018 https://doi.org/10.5045/br.2018.53.2.105

Copyright © The Korean Society of Hematology.

Busulfan plus melphalan versus high-dose melphalan as conditioning regimens in autologous stem cell transplantation for newly diagnosed multiple myeloma

Ja Min Byun1,2, Jayoun Lee3, Sang-Jin Shin3, Minjoo Kang3, Sung-Soo Yoon2, and Youngil Koh2*

1Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.

2Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.

3National Evidence-Based Healthcare Collaborating Agency, Seoul, Korea.

Correspondence to:Youngil Koh, M.D. Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongro-gu, Seoul 03080, Korea. go01@snu.ac.kr

Received: August 2, 2017; Revised: September 11, 2017; Accepted: October 23, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

High-dose melphalan (HDMEL) represents the standard conditioning regimen before autologous stem cell transplant (ASCT) in multiple myeloma (MM), but recent updates have suggested combination of melphalan with bulsulfan (BUMEL) is also associated with favorable outcomes. We performed the current study to address the lack of comparative studies between the two conditioning regimens in Asian populations.

Methods

Using the Korean National Health Insurance and Korean Health Insurance Review and Assessment Service databases, 1,304 patients newly diagnosed with MM undergoing ASCT between January 2010 and December 2014 were identified. Patients were divided according to conditioning regimen (HDMEL vs. BUMEL), and after case matching, 428 patients undergoing HDMEL conditioning were compared to 107 patients undergoing BUMEL conditioning with respect to clinical course and treatment outcomes.

Results

The 3-year progression-free survival (PFS) was 52.5% for the HDMEL conditioning group versus 70.3% for the BUMEL conditioning group (P=0.043). The 3-year overall survival (OS) was 82.0% versus 83.5% (P=0.525), respectively. Although not statistically significant, BUMEL conditioning was associated with more platelet transfusion, while HDMEL was associated with more granulocyte colony stimulating factor support. In multivariate analysis, BUMEL conditioning was not inferior to HDMEL conditioning in regard to both PFS and OS.

Conclusion

Our study confirmed that BUMEL is an effective and well-tolerated alternative to HDMEL conditioning, with better PFS.

Keywords: Multiple myeloma, Conditioning regimen, Autologous stem cell transplantation, Busulfan, Melphalan

Fig 1.

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Figure 1.(A) Overall survival compared between patients receiving high-dose melphalan conditioning regimen and patients receiving melphalan plus busulfan regimen (P=0.506). (B) Progression-free survival compared between the 2 groups (P=0.0351). MEL, HDMEL; Others, BUMEL.
Blood Research 2018; 53: 105-109https://doi.org/10.5045/br.2018.53.2.105

Table 1 . Clinical characteristics..

a)Data presented as mean (±standard deviation). b)P-values were calculated for HDMEL versus BUMEL..

Abbreviations: ASCT, autologous stem cell transplantation; BUMEL, busulfan plus melphalan; FU, follow-up; HDMEL, high-dose melphalan; MM, multiple myeloma..

Table 2 . Outcomes of autologous stem cell transplantation..

a)Data presented as mean (±standard deviation). b)The number represents the number of patients requiring platelet transfusion or G-CSF support, respectively..

Abbreviations: BUMEL, busulfan plus melphalan; G-CSF, granulocyte colony stimulating factor; HDMEL, high-dose melphalan; OS, overall survival; PFS, progression-free survival; tf, transfusion; TRM, transplantation-related mortality..

Table 3 . Multivariate analysis for progression-free survival and overall survival..

Abbreviations: ASCT, autologous stem cell transplantation; BUMEL, busulfan plus melphalan; CI, confidence interval; HDMEL, high-dose melphalan; HR, hazard ratio; MM, multiple myeloma; OS, overall survival; PFS, progression-free survival..

Table 4 . Efficacy of busulfan-based conditioning regimen for autologous stem cell transplantation in multiple myeloma patients..

Abbreviations: BUMEL, busulfan plus melphalan; CR, complete remission; HDMEL, high-dose melphalan; NA, not available; NR, not reached; OS, overall survival; PFS, progression-free survival..
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