Deletion 5q31 in patients with stable, melphalan-treated multiple myeloma.
The risk of myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML) in patients with multiple myeloma has been estimated to be 10-20% after 10 years. Most myeloma patients develop MDS/AML after 3-4 years of treatment with alkylating agents, mainly melphalan; chromosomes 5 and 7 are most frequently involved. We studied 14 patients with myeloma by fluorescence in situ hybridization (FISH) with a probe to 5q31 (the critical area of deletion on chromosome 5) to verify whether deletion of 5q31 occurs during the course of stable, uncomplicated myeloma, and to assess the clinical importance of this abnormality. We found 2 patients (14%) with deletion of 5q31 in 30-40% of their peripheral white blood cells. One patient with this deletion received a high cumulative amount of melphalan, and the other patient was treated with multiple alkylating agents, including melphalan. In these patients, no clinical or laboratory evidence of transformation occurred 14 and 12 months after the finding of the aberration. These findings suggest that 5q-may occur months prior to the overt development of (t)-MDS/AML, and raise important concerns regarding the management of patients with this and similar aberrations, including modification of treatment and performance of cytogenetic evaluation prior to autologous or PSC transplantation. The clinical and biological implications of these findings should be evaluated in larger clinical and laboratory studies.
Amiel
A
A
Department of Medicine, Meir Hospital, Kfar-Saba, Israel.
Fridman
K
K
Elis
A
A
Gaber
E
E
Manor
Y
Y
Fejgin
M
M
Lishner
M
M
D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D002273:Carcinogens / Q000009:adverse effects*; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics; D008297:Male; D008558:Melphalan / Q000009:adverse effects*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000235:genetics; D013997:Time Factors
D018906:Antineoplastic Agents, Alkylating; D002273:Carcinogens; D008558:Melphalan