Mortality and morbidity in long-term surviving patients treated with chemotherapy with or without irradiation for small-cell lung cancer.

Mortality and morbidity was investigated in a consecutive series of 72 patients with small-cell lung cancer (SCLC) who were found to be disease-free at restaging after 18 months of treatment. These patients were all the long-term survivors among 874 patients included in one of six trials between 1973 and 1981. All studies used combination chemotherapy with or without irradiation. Follow-up of the patients varied between 4 and 11 years. The estimated 5-year survival rate subsequent to discontinuation of therapy was 0.24, corresponding to a death rate of 0.25 per year or ten times greater than the expected mortality for persons of the same age group. This high mortality was primarily related to recurrent SCLC, the estimated cumulative risk of relapse reaching 46% at the time of the latest recurrence 5 years from diagnosis. The risk of relapse was generally independent of the pretreatment disease stage although it was reduced in patients with resectable disease and was greater in those with pretreatment liver or bone marrow metastases. Equal risks of relapse were related to the use of regimens with and without radiotherapy. The cumulative risk of relapse in patients surviving 3 years from initiation of the treatment was less than 15% and accordingly, 3 years of follow-up seems sufficient for comparison of long-term results obtained in different trials. The second factor resulting in death or disease was second cancer, for which the cumulated risk increased to 32%, the latest occurring 5.4 years from the diagnosis of SCLC. Five of these cases were non-small-cell lung cancers and three were secondary leukemias. The estimated mortality related to non-neoplastic conditions was just significantly greater than expected. In spite of the increased mortality in this series, 38 of 54 2-year disease-free survivors and 20 of 22 5-year survivors resumed a lifestyle similar to that before diagnosis of SCLC.

Secondary leukemia following treatment of Hodgkin's disease: ultrastructural and cytogenetic data in two cases with a review of the literature.

Two cases of secondary acute nonlymphocytic leukemia developing after combined chemo-radiotherapy for Hodgkin's disease (HD) are reported. The first case was a 28-year-old woman with PSIIIsA HD, treated with total lymphoid irradiation followed by combination chemotherapy that was almost entirely ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine), who developed acute monoblastic leukemia three years after the diagnosis of Hodgkin's disease. We believe this to be the first reported case of secondary leukemia associated with the combination of radiotherapy and ABVD chemotherapy. The second case was a 37-year-old man with Stage IVB Hodgkin's disease, treated with radiotherapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) who developed acute myeloblastic leukemia five years after the diagnosis of Hodgkin's disease. Both cases showed typical changes of panmyelosis demonstrated by cytochemical and ultrastructural studies. In both cases, bone marrow cells had a dominant clone with a markedly abnormal karyotype. The nature of therapy-related secondary leukemia after Hodgkin's disease and its relationship to current modes of treatment are discussed.

Gonadal morphology in patients receiving chemotherapy for leukemia. Evidence for reproductive potential and against a testicular tumor sanctuary.

To evaluate the possible reproductive potential in patients who receive chemotherapy for leukemia, we reviewed the gonadal histologic findings at autopsy in 183 treated leukemic patients and in 183 age- and sex-matched control subjects. The 103 male leukemic patients had significantly reduced spermatogenic activity and tubular fertility index and increased interstitial fibrosis as compared with control subjects (p less than 0.001). The 80 females had marked reduction of secondary follicles (p less than 0.001). These lesions showed no predilection for grouping by sexual maturity or by leukemia diagnosis. There was no correlation with the type of chemotherapy or time since last dose of any antileukemic agent. Despite these extensive pathologic changes, there was histologic evidence of residual reproductive potential--a tubular fertility index greater than zero in 65 percent of males and intact primary follicles in 81 percent of premenopausal females. Testicular leukemia was present in 25 percent of males; all of the patients with testicular leukemia had additional foci of leukemia in other organs. The study shows histologic evidence of possible reproductive potential in treated leukemic patients of both sexes and does not support the concept of the testis as a tumor sanctuary in leukemia.

Ultrastructural characterization of de novo and secondary leukemias.

Cells from 95 patients with acute leukemia were studied by cytochemistry, light microscopy, and transmission electron microscopy (TEM), and were classified according to the French-American-British (FAB) guidelines. This group included 63 patients with acute nonlymphocytic leukemia (ANLL) de novo, 18 with acute lymphocytic leukemia (ALL), and 14 with ANLL as a second malignancy. In addition, 13 cases of chronic myelocytic leukemia in blast crisis were studied. Ultrastructural examination resulted in reclassification of 6 cases of ANLL de novo; two of these were reclassified from M2 (myeloblastic leukemia with maturation) to M3 variant (microgranular variant of hypergranular promyelocytic leukemia). The classification of the cases of CML in blast crisis was identical by light microscopy and TEM. IN 1 case of myeloblastic crisis, however, basophilic granules were demonstrated by TEM but were not appreciated by light microscopy. Classification of the cases of secondary leukemia was possible by light microscopy and cytochemistry in all 14 cases, but was often difficult since the cytochemical reactions were usually less intense than in de novo ANLL. This was particularly true in those cases classified as M1, and in such cases, TEM was required to confirm the diagnosis.

Abolished production of interferon by leucocytes of patients with the acquired cytogenetic abnormalities 5q -- or -- 5 in secondary and de-novo acute non-lymphocytic leukaemia.

Interferon production by leucocytes on stimulation with inactivated antigens from herpes simplex virus, varicella zoster virus and cytomegalovirus was determined in 19 patients with preleukaemia or acute non-lymphocytic leukaemia, in 15 following treatment for other tumours. Production of interferon was abolished in 10 patients and preserved in nine cases after stimulation with herpes simplex antigen. Cytogenetic studies of bone marrow demonstrated an abnormal karyotype in 13/15 patients with secondary preleukaemia or leukaemia. Characteristics were (a) hypodiploid cell lines demonstrated in eight cases, (b) a B-chromosome defect found in five cases and verified as 5q -- in four, and (c) defects in C-group chromosomes in 10, verified as monosomy 7 in nine. All four patients with de-novo preleukaemia or leukaemia had abnormal cytogenetic findings, two B-chromosome abnormalities verified as monosomy 5. A relationship between abnormalities in chromosome no. 5 and abolished production of interferon was demonstrated, as only one of seven patients with 5q --, --5 or --B produced interferon by the leucocytes, compared with eight of a total of 12 patients with other cytogenetic defects or a normal karyotype (P=0.04). The results are remarkable, as chromosome no. 5 has recently been discovered to contain a gene for interferon production. Furthermore abolished production of interferon by leucocytes seemed correlated to previous irradiation and to disease-related fever.

Superficial head and neck metastases in adults with widespread cancer.

In this study of 1,782 adult patients with disseminated malignancies, superficial soft tissue cervicocephalic metastases developed in about 1 in 20. In only six patients was the primary tumor located in the head or neck, and in one of these did it involve the skin or oral mucosa. In each instance the intraoral or extraoral soft tissue metastases were clearly apparent on physical examination. Biopsy should be performed on every newly formed persistent mucocutaneous lump or bump in the head and neck to rule out not only local tumor but metastasis from remote primary lesions.