Poor Outcome With Front-Line Autologous Transplantation in t(4;14) Multiple Myeloma: Low Complete Remission Rate and Short Duration of Remission TO THE EDITOR: In younger patients with newly diagnosed multiple myeloma (MM) high-dose therapy with autologous stem cell transplantation (ASCT) is considered the standard of care since it significantly prolonged the survival in comparison with conventional chemotherapy. 1 More recently, several studies provided demonstra- tion that double ASCT was superior to a single transplantation, 2,3 particularly in patients who failed complete remission or good partial remission following the first transplantation. However, in other series double ASCT was of no clinical benefit for patients with monosomy or deletion of chromosome 13, 4 emphasizing the relevance of detecting cytogenetic and molecular abnormalities as a means to reliably predict different outcomes of the disease. The t(11;14), for example, identifies a subset of low risk MM patients who are more likely to have pro- longed duration of remission and event-free survival (EFS) following autologous transplantation. 5 At the opposite end of the spectrum, several studies, one of whom has been recently published in this journal, 6 included the t(4;14) in the list of the most adverse prognostic variables predicting for poor outcome with ASCT. 7-11 These results are consistent with those of an analysis we performed on a series of 63 previously untreated MM patients for whom bone marrow samples collected at diagnosis and stored for subsequent polymer- ase chain reaction (PCR) analyses were available. All patients were randomly assigned to receive either single or double ASCT as part of front-line therapy. 3 The clinical study was approved by local ethical committee; informed consent was provided according to the declaration of Helsinki. Using a real time-nested PCR assay designed to detect the presence of IgH/MMSET fusion gene as a surrogate marker for t(4;14), we found that 17 patients (27%) carried this cytogenetic abnormality. Comparison between pa- tients with and without IgH-MMSET hybrid transcripts showed that the two groups had similar characteristics at diagnosis, includ- ing M protein isotypes and serum beta2-microglobulin (beta2-m) levels. These results are consistent with those of a similar study, 7 but differ from data of other studies showing a higher prevalence of IgA isotype and elevated beta2-m concentrations in patients with t(4;14). 8-10 In addition, a close relationship between t(4;14) and chro- mosome 13 abnormalities was generally reported, 7,8,11 and was found also in 73% of our patients. Using an intent-to-treat approach, we found that the probability to attain stringently defined complete re- mission following melphalan 200 mg/m 2 or melphalan 140 mg/m 2 and busulfan 12 mg/kg was only 12% for t(4;14)-positive patients, compared to 39% for t(4;14)-negative patients (P = .04). Notably, in a recent study 10 resistance to alkylating agents after post-transplant relapse has been identified as a major factor contributing to the poor prognosis of t(4;14) patients treated with ASCT. With a median follow-up of 40 months from start of therapy, median EFS for our patients with and without IgH-MMSET hybrid transcripts was 23 and 32 months, respectively. The difference between the two groups was statistically significant (P = .01; Fig 1). Compared to patients without t(4;14), patients with this chromosomal abnormality also had a significantly shorter duration of remission (median, 30 months v 20 months; P = .01). In conclusion, the worsened outcome with ASCT observed in our patients with t(4;14) was related both to a higher degree of chemoresistance, that was not circumvented even by HDT, and to a disappointingly short duration of remission following ASCT. Newer and more effective treatment modalities should be explored in an attempt to improve on the dismal clinical outlook of MM patients carrying t(4;14). Michele Cavo, Carolina Terragna, Matteo Renzulli, Elena Zamagni, Patrizia Tosi, Nicoletta Testoni, Chiara Nicci, Delia Cangini, Paola Tacchetti, Tiziana Grafone, Claudia Cellini, Michela Ceccolini, Giulia Perrone, Giovanni Martinelli, and Michele Baccarani Institute of Hematology and Medical Oncology Sera ` gnoli, University of Bologna, Italy Luciano Guardigni Division of Medicine, Bufalini, Cesena, Italy REFERENCES 1. Child JA, Gareth JM, Davies FE, et al: High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 348:1875- 1883, 2003 2. Attal M, Harousseau J-L, Facon T, et al: Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495-2502, 2003 3. Cavo M, Cellini C, Zamagni, et al: Superiority of double over single autologous stem cell transplantation as first-line therapy for multiple myeloma. Blood 104:155a, 2004 (abstr 536) 4. Desikan R, Barlogie B, Sawyer J, et al: Results of high-dose therapy for 1000 patients with multiple myeloma: Durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 95:4008-4010, 2000 Fig 1. Event-free survival for 17 patients with IgH/MMSET (median, 23 months) and 46 patients without IgH/MMSET (median, 32 months) hybrid transcripts (P = .01). JOURNAL OF CLINICAL ONCOLOGY C O R R E S P O N D E N C E VOLUME 24  NUMBER 3  JANUARY 20 2006 e4 Journal of Clinical Oncology, Vol 24, No 3 (January 20), 2006: pp e4-e5 Downloaded from jco.ascopubs.org on May 18, 2011. For personal use only. No other uses without permission. Copyright © 2006 American Society of Clinical Oncology. All rights reserved.