Literature DB >> 31388085

Pretransplant hemoglobin and creatinine clearance correlate with treatment-free survival after autologous stem cell transplantation for multiple myeloma.

Karen Sweiss1,2, Gregory S Calip3, Jeremy J Johnson4,5, Damiano Rondelli5,6, Pritesh R Patel5,6.   

Abstract

Melphalan is given at a dose of 200 mg/m2 (Mel200) prior to ASCT for multiple myeloma (MM). Pharmacokinetic (PK) studies show a high degree of interpatient variability. We aimed to test the impact of clinical factors previously shown to affect melphalan PK such as hemoglobin (Hgb), fat-free mass (FFM), and creatinine clearance (CrCl) on outcomes. Median Hgb (from day -2 to -1) and FFM were grouped as low or high relative to their sample medians, and CrCl was divided into ≥60 or <60 ml/min. In 133 MM patients, median TFS (defined as time from ASCT to initiation of next subsequent line of therapy or death) was longer in patients with lower Hgb (35 vs. 16 months, p = 0.02). Patients with both lower Hgb and CrCl experienced longer TFS compared to those with higher Hgb and CrCl (35 vs. 13 months, p = 0.03). In multivariate analysis, lower hemoglobin, lower CrCl, and a combined low hemoglobin and CrCl were strongly associated with improved TFS. Patients with a lower hemoglobin or creatinine clearance experienced significantly more toxicity. We show for the first time that Hgb and CrCl are important predictors of outcomes after Mel200. PK-directed melphalan dosing may be beneficial in achieving optimal outcomes.

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Year:  2019        PMID: 31388085      PMCID: PMC7741423          DOI: 10.1038/s41409-019-0628-8

Source DB:  PubMed          Journal:  Bone Marrow Transplant        ISSN: 0268-3369            Impact factor:   5.483


  29 in total

Review 1.  Pharmacokinetics of high-dose chemotherapy.

Authors:  Y Nieto; W P Vaughan
Journal:  Bone Marrow Transplant       Date:  2004-02       Impact factor: 5.483

2.  Pharmacokinetics of melphalan in myeloma patients undergoing an autograft.

Authors:  C E Nath; P J Shaw; J Trotman; L Zeng
Journal:  Bone Marrow Transplant       Date:  2007-08-06       Impact factor: 5.483

Review 3.  Not too little, not too much-just right! (Better ways to give high dose melphalan).

Authors:  P J Shaw; C E Nath; H M Lazarus
Journal:  Bone Marrow Transplant       Date:  2014-08-18       Impact factor: 5.483

4.  Quantification of lean bodyweight.

Authors:  Sarayut Janmahasatian; Stephen B Duffull; Susan Ash; Leigh C Ward; Nuala M Byrne; Bruce Green
Journal:  Clin Pharmacokinet       Date:  2005       Impact factor: 6.447

5.  Associations of High-Dose Melphalan Pharmacokinetics and Outcomes in the Setting of a Randomized Cryotherapy Trial.

Authors:  Y K Cho; D W Sborov; M Lamprecht; J Li; J Wang; E M Hade; Y Gao; K Tackett; N Williams; D M Benson; Y A Efebera; A E Rosko; S M Devine; M Poi; C C Hofmeister; M A Phelps
Journal:  Clin Pharmacol Ther       Date:  2017-05-26       Impact factor: 6.875

Review 6.  Hematopoietic Stem Cell Transplantation for Multiple Myeloma: Guidelines from the American Society for Blood and Marrow Transplantation.

Authors:  Nina Shah; Natalie Callander; Siddhartha Ganguly; Zartash Gul; Mehdi Hamadani; Luciano Costa; Salyka Sengsayadeth; Muneer Abidi; Parameswaran Hari; Mohamad Mohty; Yi-Bin Chen; John Koreth; Heather Landau; Hillard Lazarus; Helen Leather; Navneet Majhail; Rajneesh Nath; Keren Osman; Miguel-Angel Perales; Jeffrey Schriber; Paul Shaughnessy; David Vesole; Ravi Vij; John Wingard; Sergio Giralt; Bipin N Savani
Journal:  Biol Blood Marrow Transplant       Date:  2015-03-11       Impact factor: 5.742

7.  A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome.

Authors:  M Attal; J L Harousseau; A M Stoppa; J J Sotto; J G Fuzibet; J F Rossi; P Casassus; H Maisonneuve; T Facon; N Ifrah; C Payen; R Bataille
Journal:  N Engl J Med       Date:  1996-07-11       Impact factor: 91.245

8.  Influx and efflux transport as determinants of melphalan cytotoxicity: Resistance to melphalan in MDR1 overexpressing tumor cell lines.

Authors:  Annett Kühne; Mladen Vassilev Tzvetkov; Yohannes Hagos; Hermann Lage; Gerhard Burckhardt; Jürgen Brockmöller
Journal:  Biochem Pharmacol       Date:  2009-04-05       Impact factor: 5.858

9.  Melphalan 200 mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival.

Authors:  K Sweiss; S Patel; K Culos; A Oh; D Rondelli; P Patel
Journal:  Bone Marrow Transplant       Date:  2016-05-16       Impact factor: 5.483

Review 10.  International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma.

Authors:  Shaji Kumar; Bruno Paiva; Kenneth C Anderson; Brian Durie; Ola Landgren; Philippe Moreau; Nikhil Munshi; Sagar Lonial; Joan Bladé; Maria-Victoria Mateos; Meletios Dimopoulos; Efstathios Kastritis; Mario Boccadoro; Robert Orlowski; Hartmut Goldschmidt; Andrew Spencer; Jian Hou; Wee Joo Chng; Saad Z Usmani; Elena Zamagni; Kazuyuki Shimizu; Sundar Jagannath; Hans E Johnsen; Evangelos Terpos; Anthony Reiman; Robert A Kyle; Pieter Sonneveld; Paul G Richardson; Philip McCarthy; Heinz Ludwig; Wenming Chen; Michele Cavo; Jean-Luc Harousseau; Suzanne Lentzsch; Jens Hillengass; Antonio Palumbo; Alberto Orfao; S Vincent Rajkumar; Jesus San Miguel; Herve Avet-Loiseau
Journal:  Lancet Oncol       Date:  2016-08       Impact factor: 41.316

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  2 in total

1.  Development of a method for clinical pharmacokinetic testing to allow for targeted Melphalan dosing in multiple myeloma patients undergoing autologous transplant.

Authors:  Karen Sweiss; Bhaskar Vemu; Craig C Hofmeister; Eric Wenzler; Gregory Sampang Calip; John P Galvin; Nadim Mahmud; Damiano Rondelli; Jeremy James Johnson; Pritesh Patel
Journal:  Br J Clin Pharmacol       Date:  2020-05-01       Impact factor: 4.335

2.  Survival prognostic factors in patients with acute myeloid leukemia using machine learning techniques.

Authors:  Keyvan Karami; Mahboubeh Akbari; Mohammad-Taher Moradi; Bijan Soleymani; Hossein Fallahi
Journal:  PLoS One       Date:  2021-07-21       Impact factor: 3.240

  2 in total

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