Claude Jacquillat

Post-therapeutic acute leukemia.

This study reports 35 cases of posttherapeutic acute leukemia and reviews the literature on this subject. These ALs are characterized by a high incidence of anemia, in particular refractory anemia, preceding the hematological disorder by several months, by the frequent finding of myelofibrosis, by the essentially granulocytic nature of the AL, and by the low rate of remission and the, in general, extremely short survival of a few months. These leukemias may develop following continuous chemotherapy with an alkylating agent, radiotherapy of various extent, or most commonly following intensive treatment with extensive irradiation and polychemotherapy as in the management of Hodgkins disease. In view of these therapeutic hazards, the present objectives are the modification of alkylating agent therapy by the use of other drugs and sequential administration, and a reduction in the dose and field of irradiation and the duration of polychemotherapy, as in Hodgkins disease; all present protocols are orientated in this direction.

Non-Hodgkin's lymphoma occurring after hodgkin's disease four new cases and a review of the literature

This article describes four cases of non‐Hodgkins lymphomas occurring after successful treatment of Hodgkins disease (HD). The clinical symptoms consisted of digestive disorders, and the histology confirmed an intestinal involvement in these four patients. In all cases patients had diffuse large cell types (intermediate or high grade). The respective role of HD treatment (combination chemotherapy in 3 of 4 patients with irradiation in 3 of 4 patients) and of other pathogenic hypotheses, are discussed.

Adjuvant chemotherapy in the management of primary malignant melanoma

In a prospective randomized study, the effect of chemotherapy (either systemic or combined intraarterial and systemic) was studied in 117 patients undergoing a curative resection of Clarks level III, IV or V malignant melanoma. Systemic chemotherapy was started one month after surgery one week courses with an I.V. injection of Vinblastin 6 mg/m2, Thiotepa 6 mg/m2, Rufocromomycine 60 μg/m2, Methotrexate 15 mg/m2 on day one with procarbazine 30 mg/m2 orally daily were given every other week for three months and later every four weeks. Intraarterial chemotherapy of DTIC 80 mg/kg/day for ten days was given 28 days prior to surgery. 65 patients with limb malignant melanoma were treated either by surgery only (27 patients), or by systemic chemotherapy (23 patients) or by preoperative intraarterial chemotherapy and systemic chemotherapy (15 patients): 52 patients with non limb malignant melanoma were treated either by surgery only (28 patients) or by systemic chemotherapy (24 patients). We drew curves of disease free survival following surgery and studied the levelling off of the curves, 24 months after surgery 65% of the patients treated by surgery alone were alive and free of disease whereas 81% of the patients treated by surgery and chemotherapy were alive and free of disease (p < 0.05) suggesting a possible benefit of adjuvant chemotherapy. Intraarterial preoperative chemotherapy has not proved of additional benefit to date.

Philadelphia chromosome‐positive chronic myelocytic leukemia in children survival and prognostic factors

The survival and the prognostic significance of the diagnostic characteristics of 39 children with Philadelphia chromosome‐positive chronic myelocytic leukemia (Ph1‐positive CML), seen between 1963–1976 at the Hǒpital Saint‐Louis of Paris, have been analyzed. The disease predominated in children older than age 4 years (95%), with girls being more affected than boys (24 versus 15). The clinical and hematological picture at presentation was similar to that observed in adults with Ph1‐positive CML. Most children of this series were treated with busulfan which, as in adults, led to reduction of leucocytosis and organomegaly but did not prevent the occurrence of blastic crisis. Well‐documented blastic crisis was observed in 78% of cases. Of 39 children, 12 were still alive, all in the chronic phase. Twenty‐seven have died, 21 of them after blastic crisis, 4–156 months after diagnosis (median survival, 53 months). The effect of each diagnostic characteristic on survival was evaluated using the log‐rank test. Of the 14 characteristics studied, only the degree of blood and marrow blastosis was associated with a shorter survival. Age, sex, bleeding, lymphadenopathy, hepatomegaly, degree of splenomegaly, hemoglobin level, total leucocyte, immature granulocyte (promyelocytes + myelocytes + metamyelocytes), eosinophil, basophil, and platelet counts in the peripheral blood were of no prognostic significance. The failure to attain a level of statistical significance for some characteristics found to be of prognostic value for adults, could be due to the small sample size and/or to the disease homogeneity. The results of this study, however, stress the importance of the initial blastic infiltration in determining the duration of survival, which is ultimately determined by the occurrence of terminal acute leukemia. In conclusion, this study shows that the Ph1‐positive CML of childhood exhibits the same course, incidence of blastic crisis, and survival as the disease of adults. It also indicates that treatment with moderate chemotherapy, such as busulfan, has no effect on the duration of survival. Therefore, new therapeutic approaches are urgently needed for the treatment of this disorder in children.

Chemotherapy of reticuloendotheliosis: Comparison of methotrexate plus prednisone vs. vincristine plus prednisone

Twenty‐eight children, ages 2 months to 13 years, with a diagnosis of reticuloendotheliosis were treated on a random basis with either vincristine (VCR) 2 mg/m2/week or methotrexate (MTX) 30 mg/m2 twice a week. Both groups received prednisone 40 mg/m2/day. The responders received randomly either MTX 30 mg/m2 twice weekly or no maintenance therapy. Of the 11 patients receiving VCR, 2 achieved complete and 5 partial remissions. Among 17 treated with MTX there were 8 complete and 1 partial remissions. The complete plus partial remission rate is 64% for VCR and 53% for MTX. The duration of response was superior in the MTX‐treated group, with a median remission duration of 315 days; the 4 patients above the median are still in remission. With VCR therapy, the median was 96 days, and all patients have relapsed. Maintenance therapy also improved the duration of remission, with a median of 20 months, compared to 79 days with no maintenance. Thus, in this clinical trial the best results were obtained when methotrexate plus prednisone were used for induction, followed by methotrexate maintenance therapy.

Comparison of methyl-CCNU and CCNU in patients with advanced forms of Hodgkin's disease, lymphosarcoma and reticulum cell sarcoma

In May 1972, the Cancer and Leukemia Group B initiated a randomized study comparing the effectiveness of CCNU and methyl‐CCNU in patients with advanced malignant lymphomas, including Hodgkins disease (HD), lymphosarcoma (LYS) and reticulum cell sarcoma (RCS). A single dose of 100 mg/m2 of CCNU or 150 mg/m2 of methyl‐CCNU was given orally every 6 weeks. In patients with leukopenia or thrombocytopenia, due to prior treatment, this dose was reduced to 70 mg/m2 of CCNU and 100 gm/m2 of methyl‐CCNU. Of 109 evaluable patients, 60 received CCNU and 49 received methyl‐CCNU. Response rates (complete and partial) to CCNU and methyl‐CCNU were respectively 42% (14/33) and 15% (3/20) in HD, 21% (3/14) and 21% (3/14) in LYS, 15% (2/13) and 27% (4/15) in RCS. Responses to methyl‐CCNU, but not to CCNU, were seen only in patients who developed significant hematologic toxicity. Responses to both drugs were generally of short duration due to the advanced stage of the disease. Renal, hepatic or neurological toxicity was not observed. In conclusion, CCNU proved to be superior to methyl‐CCNU for the treatment of advanced HD. CCNU was also observed to be of higher activity in Hodgkins than in non‐Hodgkins lymphomas.

Preleukemic changes in cases of nonlymphocytic leukemia secondary to cytotoxic therapy analysis of 105 cases

Peripheral blood changes preceding therapy‐related leukemia were studied in 105 patients who had received cytotoxic therapy, 53 for Hodgkins disease and 52 for other cancers. Preleukemic anomalies were observed in 74.3% of the cases, appearing after a mean interval of 68.7 months after diagnosis of the initial cancer. This interval was only 57.5 months in patients aged 50 years or older and only 42.3 months in patients with Hodgkins disease having received cytotoxic therapy for 6 months or less. The first changes most frequently observed were pancytopenia (24.8%) and isolated erythrocyte abnormalities such as anemia or macrocytosis (18.1%). Involvement of two cell lines, isolated thrombocytopenia or leukopenia, circulating immature cells, monocytosis, leukocytosis, or thrombocytosis were also observed. Therapy‐related myelodysplastic syndrome was recognized in 19 patients and myelofibrosis in 3. Median duration of the preleukemic phase was 6 months; 9 months in cases of isolated erythrocyte involvement and 5 months in the other cases. Myelomonocytic or monoblastic leukemia appeared less frequently when the first sign involved erythrocytes only. Hematological surveillance thus appears necessary in all patients having received cytotoxic therapy. Bone marrow study with cytogenetic examination should be performed in cases of persistent peripheral blood abnormalities.

Erythrocyte Mean Corpuscular Volume During Cytotoxic Therapy is a Predictive Parameter of Secondary Leukemia in Hodgkin 's Disease

Mean corpuscular volume (MCV) evolution during cytotoxic therapy was studied in 32 patients with Hodgkins disease (HD) who developed therapy‐related acute nonlymphocytic leukemia (t‐ANLL) and in 64 HD controls matched for age, therapy duration, and MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) administration. Maximum MCV during therapy reached 108.3 ± 8.2 fl in t‐ANLL patients and 103.4 ± 9.1 fl in the controls (P = 0.001). Maximum MCV increase was 26.7 ± 8.3 fl in t‐ANLL patients and 16.6 ± 8.3 fl in the controls (P = 10−9). The greatest 3‐month increase observed during therapy was 14.8 ± 6 fl in the t‐ANLL patients and 10.1 ± 4.8 fl in the controls (P = 0.0001). During initial MOPP therapy, the greatest 3‐month increase reached 14.1 ± 5.3 fl in t‐ANLL patients and 9.8 ± 4.5 fl in the controls (P = 0.01). The relative risk of developing t‐ANLL was 9 for a MCV maximum increase over 24 fl during therapy, which was observed in 71% of the patients with t‐ANLL and in only 22% of the controls. For the greatest 3‐month MCV increase over 15 fl observed in 57% of the t‐ANLL patients and in 17% of the controls, the relative risk reached 15. This suggests that there is at least one factor, independent from therapy, which predisposes to t‐ANLL. MCV evolution during therapy appears useful in determining which HD patients have a high risk of developing t‐ANLL. Cancer 59:301–304, 1987.

Prognostic value of lymphograms in chronic lymphatic leukemia

Chronic lymphatic leukemia (CLL) is a disease with a prognosis that has previously been difficult to assess. In recent years, this problem has largely been overcome by various classifications based on clinical and hematologic findings. This article presents the results of a study designed to show the value of lymphograms in assessing the prognosis. These results show that prognosis is associated with lymph node structure, as assessed by lymphography. Lymphography, as an investigation is superior to scanning or echography, since these give information merely on nodal size. It is proposed that lymphograms should be used for assessing the gravity of the disease and help in the choice of therapy.

Present Results on Daunorubicine (Rubidomycin, Daunomycin)

We have treated 1299 patients with Daunorubicine between 1966 and 1969 (Table 1). Among those patients 785 were treated at the Hopital Saint Louis with our personal protocols, 514 were treated according to protocols of ALGB. I am glad to have this opportinuty to thank Dr. J. F. Holland for his chairmanship and for his friendship.