The manuscript represents the first comprehensive analysis of a large group of uniformly treated patients with multiple myeloma and points to the overriding grave prognostic implications of chromosome 13 abnormalities. The presence of such cytogenetic aberrations was incompatible with durable disease control and long-term survival. Thus, for the first time, a separate cytogenetically defined entity of multiple myeloma has been defined, permitting basic and clinical scientists to concentrate their research efforts on patients with a dismal prognosis. In this fashion, only a brief follow-up in two to three years will be required to determine whether novel therapies display efficacy in this group of patients.

As a result of the above, both fundamental and clinical trials research can now hone in on the mechanisms associated with the exquisitely poor prognosis of chromosome 13 deletion. Traditional obstacles to advances in myeloma therapy were the tremendous heterogeneity in the clinical course of patients surviving anywhere from a few months to over a decade. As a result of focus on myeloma with chromosome 13 aberrations, new agents can be introduced into the management of myeloma patients more rapidly, also attracting the interest of members of the pharmaceutical industry, with their great potential for unique drug development.

I recognized, over 30 years ago, that cytogenetic abnormalities can define discrete clinical entities of leukemia, which have been established also in lymphoma. Those approaches paved the way to identifying the molecular mechanisms of these malignancies and enabled the development of highly specific agents, such as Gleevec, for the treatment of CML (chronic myelogenous leukemia). The situation in multiple myeloma was considerably more complex as informative (i.e. abnormal) karyotypes could be detected in only one-third of patients. When present, a profound genomic chaos was apparent in that, on average, 10 different chromosomes were involved in both structural and numeric aberrations. This genomic instability is rather unique among the hematologic malignancies and much more typical of the more common solid tumors. Painstaking efforts of scrutinizing these complex cytogenetic abnormalities in the context of a clinical readout made possible the discovery of the chromosome 13 entity.

For the patient and other laymen, the fundamental message is that the study of chromosomes in human myeloma cells more than any other test can predict the fate of a patient’s clinical course. "Knowing the enemy" is a strategy that I have embraced in my clinical practice, helping me to select the best available more therapeutic interventions for patients with poor outcome. Thus, we are practicing, at the myeloma program in Arkansas, a risk-based approach whereby we attempt to match the risk of therapeutic intervention with the risk of the disease. Specifically, we are evaluating so-called mini-allogeneic transplants from matched related and unrelated donors, which carry a higher morbidity and mortality than autologous transplants, in this setting of chromosome 13 deletion myeloma. We recommend such patients receive a mini-allotransplant after a single autotransplant, instead of the standard tandem (two) autotransplants, in order to take advantage of the major immune-controlling effect of the healthy donor immune cells toward the patient’s myeloma. In addition to mini-allotransplants, we also examine new drugs, typically reserved for more advanced and refractory disease, in this high-risk setting up front.