Correspondence

Autologous Stem-Cell Transplantation for Multiple Myeloma

N Engl J Med 2009; 361:1118-1119September 10, 2009

Article

To the Editor:

In the last sentence of their review article, Harousseau and Moreau (June 18 issue)1 state that the patient they describe had no adverse prognostic factors. However, the patient actually had three such adverse factors: a deletion of chromosome 13, a β₂-microglobulin level of 2.8 mg per liter, and a hemoglobin level of 9.8 g per deciliter.2 In a study of 110 patients undergoing autologous stem-cell transplantation for myeloma, the two most powerful adverse prognostic factors were a monosomy or deletion of chromosome 13 and a serum β₂-microglobulin level of more than 2.5 mg per liter. Median survival for patients with none, one, or two of these adverse features were more than 111 months, 47 months, and 25 months, respectively.3 In another study, patients with a chromosome 13 deletion had a significantly decreased overall survival (24 months vs. >60 months) and rate of response to chemotherapy (41% vs. 79%).4 These are key factors to take into account during the decision-making process, since a drug such as bortezomib may abrogate the adverse prognostic effect of a chromosome 13 deletion and may be useful during induction therapy before transplantation.5

Vernon J. Louw, M.B., Ch.B., M.Med.
Hymne Louw, B.Sc.
Michael J. Webb, M.B., Ch.B., M.Med.
University of the Free State, Bloemfontein, South Africa
louwvj.md@ufs.ac.za

5 References

1. 1

   Harousseau J-L, Moreau P. Autologous hematopoietic stem-cell transplantation for multiple myeloma. N Engl J Med 2009;360:2645-2654
   Full Text | Web of Science | Medline

2. 2

   Paul E, Sutlu T, Deneberg S, et al. Impact of chromosome 13 deletion and plasma cell load on long-term survival of patients with multiple myeloma undergoing autologous transplantation. Oncol Rep 2009;22:137-142
   Web of Science | Medline

3. 3

   Facon T, Avet-Loiseau H, Guillerm G, et al. Chromosome 13 abnormalities identified by FISH analysis and serum beta2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood 2001;97:1566-1571
   CrossRef | Web of Science | Medline

4. 4

   Zojer N, Konigsberg R, Ackermann J, et al. Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization. Blood 2000;95:1925-1930
   Web of Science | Medline

5. 5

   Jagannath S, Richardson PG, Sonneveld P, et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia 2007;21:151-157
   CrossRef | Web of Science | Medline

Author/Editor Response

In the large survey that led to the development of the International Staging System (ISS) in multiple myeloma, anemia was associated with a shorter survival time in univariate analysis but was not one of the most powerful prognostic indicators in multivariate analysis.1 Anemia is currently considered part of the related organ and tissue impairment that separates smoldering myeloma from symptomatic myeloma.2 In the ISS, the cutoff values for β₂-microglobulin are 3.5 mg per liter for stage II multiple myeloma and 5.5 mg per liter for stage III multiple myeloma. According to this widely accepted classification, our patient had stage I disease. The deletion of chromosome 13 is associated with a poorer outcome when it is detected with the use of conventional cytogenetic analysis.3 The references cited by Louw et al. with respect to fluorescence in situ hybridization (FISH) are old. We now know that the negative prognostic effect of the chromosome 13 deletion, as detected with the use of FISH, is actually related to other associated abnormalities, such as a t(4;14) translocation and a partial deletion on chromosome 17p. Patients who have only a chromosome 13 deletion have the same prognosis as patients who do not have this abnormality.4 The patient in our vignette had only a chromosome 13 deletion, as detected with the use of FISH, with no other adverse prognostic factors.

Jean-Luc Harousseau, M.D.
Rene Gauducheau Cancer Center, Nantes-Saint Herblain, France
jl-harousseau@nantes.fnclcc.fr

Philippe Moreau, M.D.
University Hospital Hôtel Dieu, Nantes, France

4 References

1. 1

   Greipp P, San Miguel J, Durie BGM, et al. International staging system in multiple myeloma. J Clin Oncol 2005;23:3412-3420[Erratum, J Clin Oncol 2005;23:6281.]
   CrossRef | Web of Science | Medline

2. 2

   International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working group. Br J Haematol 2003;121:749-757
   CrossRef | Web of Science | Medline

3. 3

   Stewart AK, Fonseca R. Prognostic and therapeutic significance of myeloma genetics and gene expression profiling. J Clin Oncol 2005;23:6339-6344
   CrossRef | Web of Science | Medline

4. 4

   Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood 2007;109:3489-3495
   CrossRef | Web of Science | Medline