Prolonged survival (17 years) in a patient with chronic myelogenous leukemia after therapy for Hodgkin's disease.

A case of secondary chronic myelogenous leukemia after successful therapy for Hodgkin's disease is reported. The patient was diagnosed as having stage IIIA Hodgkin's disease, at the age of 33. He underwent staging laparosplenectomy and was treated with radiotherapy plus chemotherapy. Forty three months after the diagnosis of Hodgkin's disease, a Philadelphia-positive chronic myelogenous leukemia developed. It required periodic chemotherapy and each time a remission, lasting several months (up to 14 months), was obtained. The disease had an unusually prolonged clinical course, and the blast crisis, of lymphoid type, occurred only 17 years later.

Secondary leukemia following treatment for Hodgkin's disease.

AIMS AND BACKGROUND: Patients treated for Hodgkin's disease with chemotherapy or with the association of chemotherapy and radiotherapy have an increased risk of secondary leukemia. The aim of this study was to evaluate the leukemogenic risk due to these treatment modalities. METHODS: We performed a case-control study on a population of 1410 patients treated for Hodgkin's disease from 1970 to 1990 in our Institute. Among these patients, we identified 25 cases of secondary leukemia and 3 cases of myelodysplasia, all occurring more than one year after the diagnosis of Hodgkin's disease. Three cases occurred among the patients treated with radiotherapy alone. When we analyzed the risk in relation to the type of treatment (radiotherapy, chemotherapy, or both), the comparisons were relative to patients treated with radiotherapy alone. RESULTS: We found that chemotherapy alone is associated with a fivefold increased risk (odds ratio = 5.4) compared with radiotherapy alone. When both treatments are used, the risk is not further increased (odds ratio = 4.4). Patients receiving more than 6 courses of chemotherapy have an excess risk (relative risk = 2.5) compared with those treated with 6 courses or less. No increased risk was observed after splenectomy. CONCLUSIONS: This study confirms an increased incidence of secondary leukemia occurring in patients treated for Hodgkin's disease. The increased risk seems to be correlated with the number of courses of alkylating agent therapy, whereas it is unaffected by the addition of radiotherapy.

Gastric non-Hodgkin's lymphoma: analysis of 252 patients from a multicenter study.

AIMS AND BACKGROUND: The stomach is the most common site of primary extranodal non-Hodgkin's lymphoma (NHL) and no agreement has been reached so far on the best therapeutic approach. The main objects of this study were to report the long-term results and to evaluate the importance of some possible prognostic factors in a large series of patients. NHL was considered primary gastric if the main symptoms at presentation were those of gastric disease. METHODS AND STUDY DESIGN: We analyzed 252 consecutive patients treated between 1980 and 1993 in five hospitals in north-east Italy. According to the Working Formulation, 98 patients had low grade lymphoma, 59 intermediate grade (D to F), 81 G or high grade and 14 were not classified. The patients were divided into two groups: one including patients with limited disease (localized to the stomach or perigastric lymph nodes: 165 patients) and one including those with advanced disease (87 patients). The treatment consisted of surgery, chemotherapy, radiotherapy or combinations of these. Sixteen patients received only supportive therapy. RESULTS: The five-year overall survival was 65.4%: 80.3% for patients with limited disease and 36.7% for those with advanced disease (P < 0.0001). Among the limited disease patients the five-year survival was 84.4% for those treated with gastrectomy alone and 88.7% for those who received also adjuvant chemotherapy (P = 0.11). However, while chemotherapy did not improve survival in low grade NHL, it seemed to produce a better survival in the intermediate and high grade groups (P = 0.06). Twelve patients were treated with primary chemotherapy and the five-year survival was 71.2%. In multivariate regression analysis the most important variable for overall survival was surgery for the whole group of 252 patients (P < 0.0001), while it was age for the group with limited disease (P = 0.0008). CONCLUSIONS: Surgery alone can be curative for most patients with gastric lymphoma limited to the stomach or to the perigastric lymph nodes; surgery followed by chemotherapy seems to produce better results than surgery alone in intermediate and high grade lymphomas. Also a non-surgical approach with first-line chemotherapy is associated with a high rate of complete remissions and five-year survival. In advanced disease the five-year survival is similar to that of nodal NHL.

Allogeneic hemopoietic SCT for patients with primary myelofibrosis: a predictive transplant score based on transfusion requirement, spleen size and donor type.

A total of 46 patients with primary myelofibrosis (PMF) (median age 51 years), underwent an allogeneic hemopoietic SCT (HSCT) after a thiotepa-based reduced-intensity conditioning regimen. The median follow-up for surviving patients is 3.8 years. In multivariate analysis, independent unfavorable factors for survival were RBC transfusions >20, a spleen size >22 cm and an alternative donor-24 patients had 0-1 unfavorable predictors (low risk) and 22 patients had 2 or more negative predictors (high risk). The overall actuarial 5-year survival of the 46 patients is 45%. The actuarial survival of low-risk and high-risk patients is, respectively, 77 and 8% (P<0.0001); this is because of a higher TRM for high-risk patients (RR, 6.0, P=0.006) and a higher relapse-related death (RR, 7.69; P=0.001). In multivariate Cox analysis, the score maintained its predictive value (P=0.0003), even after correcting for donor-patient age and gender, Dupriez score, IPSS (International Prognostic Scoring System) score pre-transplant and splenectomy. In conclusion, PMF patients undergoing an allogeneic HSCT may be scored according to the spleen size, transfusion history and donor type; this scoring system may be useful to discuss transplant strategies.

Late relapses in Hodgkin's disease: outcome of patients relapsing more than twelve months after primary chemotherapy.

BACKGROUND: Patients with Hodgkin's disease whose initial complete remissions (CR) after primary chemotherapy were longer than 1 year are thought to have better prognoses than patients whose initial remissions were shorter than 1 year. However, only a few studies have analyzed the long-term survival in addition to the results of retreatment in patients relapsing after CR lasting more than 1 year. PATIENTS AND METHODS: We analyzed the data of 40 patients with Hodgkin's disease who were treated in a single institution and whose CR were > 1 year after primary chemotherapy. Therapy at relapse was not standardized: of 36 patients evaluable for response, 29 received second-line chemotherapy and 7 received radiotherapy alone. RESULTS: Sixty-five percent of the patients obtained CR (median duration: 21 months). Sixty-eight percent of the complete responders relapsed again; however, long-lasting third and fourth remissions were observed. All of the 7 patients whose retreatment consisted of radiotherapy alone obtained CR, but only 1 is in continuous CR. The presence of nodular sclerosing histologic subtype, the absence of extranodal involvement and the use of hybrid MOPP/ABVD or ABVD alone as salvage treatment are independently associated with a higher CR rate and a higher probability of 5-year survival. The 5-year survival for all 40 patients is 49%. For the patients obtaining CR, the 5-year survival and the 5-year relapse-free survival are 76% and 25%, respectively. However, the survival curve continues to fall in the succeeding years because of third and fourth relapses and the occurrence of secondary acute leukemia and non-Hodgkin's lymphoma. CONCLUSIONS: A high percentage of patients relapsing more than 12 months after primary chemotherapy can obtain second CR. Even if most of our patients eventually relapse, third and fourth CRs are not uncommon. However, the long-term survival is low and it is further diminished by secondary leukemia and non-Hodgkin's lymphoma.

A combination of mitoxantrone, etoposide and prednisone in elderly patients with non-Hodgkin's lymphoma.

From January 1988 to December 1991, 55 elderly patients (14 pretreated and 41 previously untreated) with non-Hodgkin's lymphoma (NHL) entered a prospective study to evaluate the feasibility of a combination of mitoxantrone (7-9 mg/m2), VP 16-213 (150 mg, 2-hour infusion on day 1, and 200 mg per os on days 3 and 5) and low-dose prednisone (25 mg days 1-5) (MVP regimen), recycling every 21-28 days. The median age was 75 (range 64-93). All but 4 pretreated patients had intermediate- or high-grade lymphomas. Complete remissions were obtained in 22 of 40 (55%) evaluable previously untreated patients, and partial remissions in 10 (2 of these obtained complete remissions after radiotherapy), for an overall response rate of 80%. The median duration of response was 12 months. At 24 months the overall survival was 52% and the relapse-free survival was 31%. Of 14 pretreated patients complete remissions were obtained in 4 (29%) and partial remissions in 3. Granulocytopenia and fever were the most important side effects; two patients contracted bronchopneumonia and one of them died. Other toxicities were mild. We conclude that this combination chemotherapy is effective as first-line and salvage treatment in elderly patients with intermediate- and high-grade NHL, and that it is feasible on an outpatient basis, with manageable toxicity.

Hybrid MOPP/ABVD and radiotherapy in advanced Hodgkin's disease.

BACKGROUND: In patients with advanced Hodgkin's disease (HD), the alternation of MOPP with ABVD or hybrid MOPP/ABVD are associated with a high CR rate and a high probability of 5-year survival. However, even after effective chemotherapy the risk of nodal relapse is not negligible, and not only in initial bulky site(s) of disease. For this reason, in an attempt to prevent relapses after combination chemotherapy alone, we performed a prospective study to evaluate the efficacy and toxic effects of 6 courses of hybrid MOPP/ABVD followed by radiotherapy (RT) in stages II A bulky, II B, III and also in stage IV with bulky disease of residual after chemotherapy. PATIENTS AND METHODS: From January 1985 to August 1993, 133 patients with HD (128 newly diagnosed, stage II A bulky-IV, 5 in first relapse after RT) were treated according to the following program: 6 courses of the hybrid MOPP/ABVD regimen followed by RT (STNI + spleen in stages II A, II B, III without pelvic lymph node involvement, TNI + spleen in stage III with pelvic lymph node involvement, involved field in stage IV with bulky disease or residual after chemotherapy). The total dose of RT was 4000 cGy to the sites of bulky or residual disease and 2000 cGy to the other sites. RESULTS: After hybrid MOPP/ABVD, 107 of 130 (82.3%) fully evaluable patients were classified as in CR or CR(U). After completion of RT, 108 patients were in CR and 3 were in PR, for an overall response rate of 85%. With a median follow-up duration of 45 months, the actuarial 5-year survival is 76% and the progression-free survival 68.6%. So far, only 14 patients have relapsed (6 within the irradiation field) and the 5-year relapse-free survival is 82.5%. CONCLUSION: Six courses of hybrid MOPP/ABVD followed by RT in stages II A bulky, II B, III and in stage IV with bulky disease or residual after chemotherapy produced a high CR rate with low risk of relapse. However, a longer follow-up is necessary to evaluate the late effects of combined therapy.