Highlights From the 39th Annual Meeting of the American Society of Hematology
More than 14,000 people from all over the world congregated in San Diego’s Convention Center December 5-9, 1997, for the annual meeting of the American Society of Hematology.
One major attraction of this meeting is the blend of basic and clinical science and the very broad range of topics presented. The Plenary Session illustrated this point as presentations on the differentiation of hematopoietic stem cells and the influence of telomere shortening on cell fate were presented together with clinical trial results in allogeneic bone marrow transplantation and sickle cell disease.
We discussed above the issue of whether interferon therapy alters the efficacy of a subsequent matched sibling donor allogeneic bone marrow transplant in CML. A plenary abstract from the University of Washington addressed the influence of prior interferon therapy on the course of allogeneic bone marrow transplants using unrelated donor marrow in CML. Outcome was assessed in 183 patients in chronic phase. Patients who had received interferon therapy for six months or longer before the transplant had significantly more severe acute graft-vs.-host disease and poorer survival. However, for the group of patients less than 51 years old, receiving marrow matched at HLA-A, -B, DRB1, and DQB1, receiving CMV and fungal prophylaxis, and receiving interferon for less than six months before receiving the transplant, five-year survival was 87%. (Morton AJ, et al. Blood 1997;90(suppl 1):#535, 123a.)
Also presented in the Plenary Session was an interim analysis of the European Acute Promyelocytic Leukemia Group study comparing all-trans retinoic acid (ATRA) followed by combination chemotherapy vs. ATRA plus chemotherapy induction. Ninety-three treatment centers contributed 403 patients with acute promyelocytic leukemia and a peripheral white blood count of greater than 5000. One group received 45 mg/m2 ATRA daily until they reached a complete response, and then they received cytarabine and daunorubicin leukemia induction therapy. The other received the same dose of ATRA with chemotherapy beginning on day 3. Also included was a randomization to two different consolidation and maintenance treatments. Preliminary analysis suggests that the use of ATRA together with chemotherapy results in significantly fewer relapses. (Fenaux P, et al. Blood 1997;90 (suppl 1):#533, 122a.)
A phase II Southwest Oncology Group study of fludarabine in patients with Waldenstrom’s macroglobulinemia produced disappointing response rates. Prior single institution studies involving small numbers of patients had suggested that fludarabine may be nearly as active in Waldenstrom’s macroglobulinemia as in chronic lymphocytic leukemia. However, a phase II study in 210 patients found an overall response rate of only 34% and complete response rate of 15%. Patients who were previously untreated had better progression-free survival, 42 months vs. 27 months. Frankly, I expected better results. Nevertheless, the drug is comparably active in previously untreated patients and in those who have received alkylating agents. (Dhodapkar M, et al. Blood 1997;90(suppl 1):#2571, 577a.)
Antibiotic therapy works in gastric MALT lymphoma, but in myeloma? Durie and colleagues wondered whether there might be bacterial antigens driving myeloma cell proliferation as well, based upon detecting circulating sequences containing what appeared to be a bcl1/JH region fusion similar to some patients with MALT. They administered 500 mg clarithromycin twice a day to 30 patients. Follow-up is quite short, but 13 patients have had major regressions, six have had stable disease, four have had mixed responses, and seven are too early to evaluate. Clearly, the rationale for this intervention is debatable, but most would consider it pretty flimsy. However, the reported clinical results are surprisingly good. It is now important to try to understand whether the result is related to some unknown direct antitumor effect of the drug or whether there is some bacterial antigen driving the proliferation of the tumor cells. (Durie BGM, et al. Blood 1997;90 (suppl 1):#2577, 579a.)
Preliminary analysis of the efficacy of ATRA used together with chemotherapy revealed that the combination:
a. had no effect.
b. resulted in more relapses.
c. resulted in fewer relapses.
d. could not be evaluated.
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