NITROGEN MUSTARD THERAPY IN HODGKIN’S DISEASE: Analysis of Fifty Consecutive Cases

Abstract

Abstract 1. Methyl bis (B chloroethyl) amine (HN2) was given by intravenous route for the treatment of 50 successive cases of Hodgkin’s disease, most of them severe and far advanced. Doses somewhat smaller than the usually recommended amount of 0.1 mg. per Kg. were used in courses of four to six injections. 2. Nausea and vomiting followed administration of the drug in 93.2 per cent of cases. Chills and fever occurred in 12.4 and 6.8 per cent of cases respectively. Dyspnea, cyanosis and diarrhea were rare. 3. In previously untreated cases, remissions were of much shorter duration than those obtained with Roentgen therapy. However, striking remissions were commonly obtained in x-ray resistant cases. Remissions lasted from 17 to 331 days and in individuals receiving multiple courses were roughly proportional to the total dosage administered. A moderate prolongation of the remission period was obtained when HN2 was combined with roentgen therapy. 4. Constitutional symptoms such as fever, night sweats, weakness and itching responded exceedingly well in most cases to HN2 therapy. Many previously incapacitated patients were completely rehabilitated for several weeks to several months after a single course of HN2 therapy. 5. Adenopathy and splenomegaly regressed in 70.2 and 71.7 per cent of cases respectively. Lymphoid masses previously resistant to x-ray therapy appeared to develop increased sensitivity to x-rays after a course of HN2 therapy. 6. Patients with extensive mediastinal involvement and obstructive symptoms responded only moderately well while those with lesser degrees of involvement showed a better response. 7. Paraplegia due to intraspinal involvement was partially relieved in half the cases while pain due to similar involvement was dramatically relieved in all cases. Pain due to pressure upon peripheral nerves was similarly relieved in all cases. 8. A slight but definite fall in the erythrocyte and hemoglobin levels occurred within five to six days after the institution of therapy. Reticulocytes were maximally depressed on the sixth to tenth days. Of the leukocytic elements, the granulocytes were predominately affected, with maximal cytopenic levels on the twenty-first to twenty-fifth day. The leukocytes gradually returned to normal by the thirty-sixth to fortieth day. Cases presenting an initial leukopenia tended to develop normal leukocyte counts after an initial drop to low levels. The platelet count was affected in only 20.5 per cent of cases. Terminal cases at times developed marked pancytopenia. 9. In one case severe hemorrhagic complications due chiefly to thrombocytopenia followed the administration of the tris form of nitrogen mustard and gradually subsided after a very stormy course. 10. Progressive but temporary marrow hypoplasia followed nitrogen mustard therapy in eleven cases studied with serial marrow punctures. Erythroblastic depression was noted within twenty-four hours and granulocytic depression within forty-eight to seventy-two hours. The megakaryocytes proved to be the most resistant of the marrow elements. The marrow picture usually returned to normal spontaneously within a period of six to eight weeks after the cessation of therapy. 11. Lymph node punctures revealed degeneration and pyknosis of lymphocytes within twenty-four hours after the institution of therapy with a subsequent gradual disappearance of polymorphonuclear neutrophiles, eosinophiles, plasma cells, reticulum cells and Dorothy Reed cells. Miliary foci of necrosis were demonstrated in a gland obtained at post mortem seven days after the institution of HN2 therapy. 12. Miliary foci of necrosis were demonstrated in the liver of 3 cases dying between nine and nineteen days after the institution of HN2 therapy. No such findings could be found in a case in which death occurred fifty-four days after the initiation of therapy. 13. The therapeutic results with HN2 in Hodgkin’s disease appeared to have little relationship to the histologic appearance of the involved tissue. The immediate response in so-called Hodgkin’s sarcoma was particularly striking, and in one case, a remission lasting about a year took place.