Beta-2-Microglobulin: Prognostic Indicator in Early Stage Hodgkin’s Disease

Abstract & Commentary

Synopsis: Of 217 consecutive Hodgkin’s disease patients seen at M.D. Anderson with Stage I or II disease who received chemo- and radiation therapy, 12 had elevated b2M (> 2.5 mg/L). There was a trend for reduced relapse-free survival for those with elevated levels, and a significant correlation with reduced overall survival. Thus, an inexpensive and widely available laboratory measure might provide useful prognostic information in patients with Hodgkin’s disease.

Source: Chronos GM, et al. Cancer. 2002;95: 2534-2538.

Over an 8-year period (1987-1995) 217 consecutive patients with Stage I or II Hodgkin’s disease (HD) were treated at M.D. Anderson Cancer Center in Houston with initial chemotherapy and radiation. Patients received a median of 3 cycles of combination chemotherapy followed by radiation. In the current report, various clinical features were examined to determine if they were of prognostic significance. Medical records were reviewed including beta-2-microglobulin (b2M), albumin, gender, and presence of bulky disease and relapse-free survival (RFS) and overall survival (OS) were recorded.

Patients were followed from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3 or more years. All patients were free of HD at the end of treatment. Twenty-eight patients developed recurrence and of these, 19 have died. The 5-year RFS and OS were 88% and 95%, respectively. A serum level of b2M > 2.5 mg/L was considered elevated and this level or higher was found in 12 of the patients.

With regard to RFS, male gender and bulky disease were statistically significant adverse prognostic factors (P < 0.05) on both univariate and multivariate analysis. There was a trend toward elevation of the serum b2M level also representing an adverse prognostic factor. However, with regard to OS, only b2M was a significant adverse prognostic factor on univariate and multivariate analyses.

Comment by William B. Ershler, MD

b2M is a single chain polypeptide of unknown function linked to the major histocompatibility complex Class I cell surface antigen.1 Its presence in serum reflects lymphoid cell turnover, and elevated levels have been associated with a number of malignancies including multiple myeloma, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and HD. In fact, b2M levels have been shown to correlate with stage in HD, and elevated levels have correlated with less favorable prognosis.2-4 The current study adds strength to this correlation, inasmuch as the follow-up period was of sufficient duration that an association of elevated b2M with overall survival could be determined. However, it should be remembered that this was a retrospective analysis of a subset of HD patients (early stage disease, treated at a single institution), and only 12 patients had high b2M levels.

These caveats notwithstanding, a simple, widely available and inexpensive laboratory test may be of great value as a predictor of unfavorable outcomes, and thus may be useful in identifying those patients for whom more aggressive therapy is warranted. However, it would be premature to hinge clinical decisions on the b2M level. Such would be the recommendation only after the current findings are confirmed in a larger, multi-institutional analysis. Even then, b2M is likely to be just one of several prognostic factors, along with age, gender, presence of bulky disease, leukocytosis and lymphocytopenia, that may ultimately guide clinicians to the appropriate treatments for early stage HD. 

Dr. Ershler of INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.

References

1. Grey HM, et al. J Exp Med. 1973;138: 1608-1612.

2. Dimopoulos MA, et al. J Clin Oncol. 1993;11: 1108-1111.

3. Melillo L, et al. Tumori. 1988;74:129-135.

4. Hagberg H, et al. Cancer. 1983;51:2220-2225.