tumor. Spitz (1948) conducted a histological analysis of postmortem tissue of 57 cases consisting of a variety of lymphomas, leukemias, and other malignant tumors treated with nitrogen mustards. Attributable to mustard therapy in these cases was a consistent, apparently accumulative hypoplasia of bone marrow. This hypoplasia was correlated with the degree of leukopenia and thrombocytopenia that had existed prior to death.
The immunosuppressive effects of alkylating agents have also been demonstrated in treating autoimmune disease and as adjunctive therapy in organ transplantation procedures, to prevent rejection by the recipient. Immunosuppressive treatments, like exposure to sulfur mustard, result in increased incidence of infectious disease. There is a well-established association between the therapeutic use of chemical immunosuppressants, such as those used in organ transplant therapy, and an increased incidence of infectious disease in humans (Ehrke and Mihich, 1985).
Evidence from animal experiments consistently confirms that mustard agents affect immune system functions. Animal models are most valuable in studying the physiological and molecular mechanisms involved in mustard agent effects. In general, this review accorded greater weight to data derived from studies in more than one animal species or test system, on results that have been reproduced in different laboratories and on data that indicated a dose-response relationship. However, results from animal studies cannot be used alone either to affirm or to negate relationships between exposure to mustard agents and chronic disorders, nor can they be used to estimate accurately the size of the effects in humans.
Clinical observations in humans provide the most direct evidence of the immunologic effects of mustard agents. In this review, greater significance was accorded to observations in humans that provide clear evidence that mustard agent exposure is associated with bone marrow toxicity expressed as leukopenia, pancytopenia, or a plastic or hypoplastic bone marrow. Underrepresented in these works is information on chronic or delayed effects. This may be attributable to the fact that patients, if they survive the acute effects, experience a number of secondary infections and may in fact die from them. Finally, the data presented here indicate that clinical studies as a whole support a close parallelism between animal experiments and observations in humans regarding the immunosuppressive properties of mustard agents.