Risk of secondary acute leukemia and preleukemia after Hodgkin's disease: the Institut Gustave-Roussy experience.

From 1960 to 1984, 871 patients were treated for Hodgkin's disease at the Institut Gustave-Roussy. Twenty-six percent of the cohort were treated with radiotherapy (RT) alone, 6% with chemotherapy (CT) alone, and 68% with a combination of RT and CT, either at first line or for salvage treatment. MOPP chemotherapy was given to 42% of the patients. Overall, 19 secondary acute leukemias or preleukemias were observed, 3 of them after extended RT alone, the other 16 after a combination of RT and MOPP. Among the alkylating agents used, only nitrogen mustard (mechloretamine) was shown in a multivariate analysis to be significantly associated (P less than 0.001) with an increased risk of secondary leukemia. A dose response was observed, with the risk relative to general population incidence rates being 45 in patients having been treated with 1-59 mg (total dose) of nitrogen mustard, 211 in those treated with 60-119 mg, and 636 in those treated with greater than or equal to 120 mg. No other factors were found to be associated with leukemia risk. The 10-year cumulative incidence of leukemia was zero in patients treated with limited RT alone, 2.4% in those treated with extended RT alone, 0% in those treated with a combination of RT and CT without nitrogen mustard, and 12.4% in those treated with RT + nitrogen mustard. Whether other alkylating agents give a similar result remains to be determined; these data suggest that the use of nitrogen mustard at a higher total dose than 60 mg is questionable in the treatment of Hodgkin's disease.

Subacute and chronic myelomonocytic leukemia in children (juvenile CML). Clinical and hematologic observations, and identification of prognostic factors.

The clinical and hematologic characteristics of 38 children with subacute and chronic myelomonocytic leukemia (S & CMMOL) are described, and the prognostic significance of these characteristics as recorded at diagnosis is reported. The common and distinctive feature of these children was the excessive proliferation of cells of neutrophilic and monocytic series. The disease predominated in younger children, 95% were younger than 4 years, and boys were more affected than girls (22/16). The onset of the disease was heralded most often by acute or subacute symptoms. Splenomegaly was the most common physical finding at diagnosis. Leukocytosis was usually under 100 X 10(9)/l. Monocytosis and granulocytosis were often associated with normoblastosis, and, in some cases, with moderate blastosis (less than or equal to 30%). Severe anemia and marked thrombocytopenia were found in about one third of patients, increased fetal hemoglobin levels in 53%, and increased gamma-globulin levels in 50% of cases. The Philadelphia chromosome was absent in all blood and marrow cell karyotypes. Thirty-three of 38 patients were treated with moderate or intensive chemotherapy, and in all cases treatment never resulted in a complete remission. Terminal acute leukemia occurred in 11 cases. Of the 38 patients, 29 have died (median survival time, 16 months). Initial characteristics predicting a short survival (log-rank test) included: older age (greater than or equal to 2 years) (P less than 0.001), hepatomegaly (P less than 0.05), bleeding (P less than 0.001), thrombocytopenia (P less than 0.01), high counts of blasts and normoblasts in peripheral blood (P less than 0.01, P less than 0.01). Sex, infections, cutaneous manifestations, lymphadenopathy, degree of splenomegaly, hemoglobin levels, fetal hemoglobin, leukocyte counts, percent of blasts in bone marrow, and serum gamma-globulin levels were of no prognostic value. When survival was plotted on a semilogarithmic scale, a change in death rate was evident at the second year of survival suggesting that there may be two subgroups of patients with myelomonocytic picture, one with very rapid, and another with a slower rate of mortality. A stepwise discriminant-function analysis was performed in an attempt to distinguish between those children who lived less than or equal to 2 years and those who lived longer. A linear combination of variables which best discriminated between these two subgroups was found. Nearly all patients could be classified as a short-survivor or long-survivor on the basis of age and platelet, blast, and normoblast counts in peripheral blood.(ABSTRACT TRUNCATED AT 400 WORDS)

Hodgkin's disease in children. Results of therapy in a mixed group of 178 clinical and pathologically staged patients over 13 years.

One hundred seventy-eight previously untreated children with biopsy-proven Hodgkin's disease of clinical Stages I and II were treated and followed between 1965 and 1978. Staging laparotomy was performed in 30 patients. Ninety-four percent of the patients obtained a complete remission; 24 patients have died. The actuarial survival rate for all patients was 90% at 5 years, and 81% at 10 years. The disease-free survival rate was 69% at 5 years, and 65% at 10 years. When nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was added to either extended field or involved field irradiation, the relapse rate was significantly decreased as compared with the protocols without MOPP and prophylactic para-aortic irradiation. The authors believe that surgical staging may not be necessary as splenic involvement may be treated in some patients by MOPP chemotherapy alone or in association with splenic paraaortic radiotherapy. However, the side effects of MOPP need further study by other chemotherapy programs.

[Possibilities of treatment of reduction in Hodgkin's disease. III. Can polychemotherapy when combined with radiotherapy of localised stages be reduced? (author's transl)]. / Möglichkeiten einer Therapiereduktion bei Morbus Hodgkin III. Kann die Polychemotherapie bei einer kombinierten Chemo-Strahlentherapie lokalisierter Stadien verringert werden?

The effectiveness of three and six cycles of MOPP (chlormethine, vincristine, procarbazine and prednisolone) as initial chemotherapy in 108 patients with Hodgkin's disease at clinical stages II nA, IIB, IIIA and B was compared in a study of two groups, one of them treated in six cycles (October, 1972--December, 1976), the other in three cycles (January, 1977--October, 1979). The clinically complete remissions obtained by this schedule and findings at exploratory splenectomy were chosen as measures of effectiveness. The frequency of clinically complete remission was similar in both groups. In 96% (97% for the second group) of patients in whom the three (six) MOPP cycles of cytostatic treatment achieved clinically complete remission, exploratory splenectomy failed to reveal any infradiaphragmatic involvement. In patients in stage IIA and IIB one can, therefore, consider reducing primary cytostatic treatment to three MOPP cycles. Exploratory splenectomy and prophylactic infradiaphragmatic radiotherapy can be omitted in these patients, if one accepts the 5% risk of infradiaphragmatic involvement. Splenectomy can also be omitted in patients in stage III, but not infradiaphragmatic radiotherapy, including that no the spleen.

Chemotherapy--radiotherapy association in Hodgkin's disease, clinical stages IA, II2A: results of a prospective clinical trial with 166 patients.

One hundred sixty-six patients with clinical stages IA, II2A Hodgkin's disease were treated between April 1972 and December 1976 with three courses of multiagent chemotherapy (methylchlorethamine, vincristine, procarbazine, prednisone) followed by mantle irradiation--excluding mediastinum for those with initial upper cervical presentation and absence of mediastinal involvement--or inverted Y radiotherapy. None had staging laparotomy. With a follow-up of 12--84 months, median 40 months, the overall survival is 93.5% and the overall relapse-free survival 89.9%. Eight patients died, three of them with evident disease. Ten patients relapsed; four are now free of disease after retreatment. With chemotherapy-radiotherapy sequence, staging laparotomy is not indicated. Results and side effects of this treatment strategy are compared with those of other treatment policies.

["Transparent circles" lymph glands: an unusual appearance on lymphography in certain proliferative lymphoid syndromes: prognostic value]. / Les ganglions "cerclés transparents". Aspect inhabituel de la lymphographie dans certains syndromes lympho-prolifératifs. Intêrêt pronostique.

The authors describe 27 cases in which a very particular type of lymphographic image was observed, associating disseminated lesions in all the retroperitoneal lymph glands, and an appearance of "circled" glands of very weak density. This image may be rarely observed in Hodgkin's disease and non-Hodgkin type hematosarcomas. It is frequently observed, however, during the course of angio-immunoblastic lymphadenopathy. Whatever the etiology, this image is of particularly poor prognostic significance.

[Possibilities of treatment reduction in Hodgkin's disease (author's transl)]. / Möglichkeiten einer Therapiereduktion beim Morbus Hodgkin. II. Ermöglicht eine primäre Polychemotherapie den Verzicht auf eine explorative Splenektomie bei klinisch lokalisiertem Krankheitsbefall?

Exploratory laparotomy with splenectomy was performed before or after multiple chemotherapy in 182 patients with clinically localised Hodgkin's disease in clinical stages IB, II3A, IIB, III A and III B. There was a 50% probability of clinically not diagnosed infradiaphragmatic involvement in patients with clinically localised stage IB, II B or II3A. Restaging was necessary in 20% of patients with clinical stage III, because infradiphragmatic involvement was histologically not demonstrable. Infradiaphragmatic involvement occurred in 12% of patients who had received six chemotherapy cycles according to the MOPP scheme, before exploratory splenectomy. When chemotherapy produced complete clinical remission, only 2.7% patients had any infradiaphragmatic involvements. Exploratory laparotomy with splenectomy is not required, therefore, in such patients.

[Possibilities of radiation-dose reduction in the treatment of Hodgkin's disease. I. Exclusion of the mediastinum from the radiation field in primary high-cervical or infradiaphragmatic involvement and stage I or II (author's transl)]. / Möglichkeiten einer Therapiereduktion beim Morbus Hodgkin. I. Aussparung des Mediastinums aus dem Strahlenfeld bei primär hochzervikalem oder infradiaphragmalem Befall und Stadium I oder II.

A retrospective analysis on 482 patients with localised Hodgkin's disease revealed that none of those with primary high-cervical or primary infradiaphragmatic involvement had any infiltration of the mediastinum, either at the time or later. As a result, prophylactic mediastinal radiation was not practised if high-cervical or infradiaphragmatic lymph-nodes had been affected first. None of these patients had any mediastinal recurrence after at least seven years.