Spontaneous Remission of Chronic Lymphocytic Leukemia: An Update

Abstract

In 1904, Dock reported the following: “Summary of the case: A woman with mixed-cell [myelogenous] leukaemia, with greatly enlarged spleen. Two weeks after an attack of what was probably influenza, the leukocytes were found reduced from 367,070 to 7500…The spleen was much smaller; the liver became smaller later…[and both] remained small for many months…Such a change…forces one to try to learn something from it…of therapeutic value.” Since Dock’s observation, (American Journal of the Medical Sciences 127 (1904), 563-592) there have been additional well-documented cases in which the progress of cancer was interrupted temporarily by intercurrent infection. (Bierman et al., Cancer 6 (1953), 591; Einhorn M, Journal of the American Medical Association 175 (1961), 1006; Paolino W et al., Minerva Medica 51 (1960), 3454; Pelner L et al., Acta Medica Scandinavica suppl 338 (1958), 1.) Among the experiments done in this field to induce infection as a therapeutic measure, those of Southam and Moore (Cancer 5 (1952), 1025; American Journal of Tropical Medicine 3 (1954), 19) with West Nile virus in humans with advanced lymphoma are the most meaningful. Evidence of tumor regression was observed in 4 patients. The present report describes tumor regression in 4 individuals with advanced lymphomas (3 patients with lymphosarcoma and 1 patient with Hodgkin’s disease) inoculated with an attenuated strain of Venezuelan equine encephalomyelitis virus. Inoculation was followed by objective evidence of regression of tumor masses; this was associated with obvious subjective improvement in 3 of the patients. It was preceded by a febrile illness, with a temporary suppression of circulating leukocytes and platelets. Overt clinical encephalitis did not occur in these patients, and neither clinical nor histological evidence of encephalitis was found in 4 preterminal patients similarly inoculated.

Case Details

Personal Characteristics

The cohort included seven males and four females. Their ages ranged from 37 to 69 years at the time of diagnosis.

Clinical Characteristics

Six had stage 0, 3 had stage ii and the remaining two had stage iii disease. One patient with stage iii had two partial remissions with chlorambucil therapy followed by relapses some years before the spontaneous disappearance of all peripheral manifestations of her disease. Another patient with stage iii had two transient partial remissions with triethylene melamine therapy prior to the spontaneous remission; he died of bronchogenic carcinoma 14 years after the diagnosis of leukemia and 7 years after the onset of his spontaneous remission.

Remission Characteristics

Spontaneous remission was observed several years after the diagnosis in seven patients (six with stage 0 and one with stage ii disease); five of those are still alive and two have died of unrelated cause. A complete autopsy was carried out on one case and no microscopic evidence of leukemia was found.

Treatment & Mechanisms

Proposed Remission Mechanisms

Upper respiratory infection was noted prior to the onset of spontaneous remission in 2 of 11 patients with cll in the present study. Ribera and associates (blood cells 12 (1986), 471-479) observed viral infection (varicella zoster) in one case and possible viral infection (bilateral orchitis) in another case among three cases of spontaneous remission. Viral infections also preceded spontaneous remission in two cases reported by others. (vladimirskaia eb, problem gematologii i perelevaniya krovi, 7: 1962, 51-54 and bousser j, novelle revue franchise d’hematologic 5 (1965), 498-601.) in two additional patients, spontaneous remission was related to smallpox vaccination. (hansen rm, archives of internal medicine 138 (1978), 1137 and yettra m, archives of internal medicine 139 (1979), 603.) these observations suggest that viral infection may play a role in the induction of spontaneous remission in some cases.

Clinical Treatment

One patient with stage iii had two partial remissions with chlorambucil therapy followed by relapses. Another patient with stage iii had two transient partial remissions with triethylene melamine therapy.

Additional Notes

Spontaneous remission in CLL may not be as rare as previously thought.