Anna Paola Anselmo

Hodgkin/Reed-Sternberg cells and Hodgkin's disease in patients with B-cell chronic lymphocytic leukaemia: an immunohistological, molecular and clinical study of four cases suggesting a heterogeneous pathogenetic background.

Abstract We report the immunohistological, molecular and clinical findings in four patients affected by B-cell chronic lymphocytic leukaemia (CLL) who developed ”Richter’s syndrome with Hodgkin’s disease (HD) features” or ”CLL with Hodgkin’s transformation”, all characterised by the presence of typical Hodgkin / Reed-Sternberg (H/RS) cells in lymph node biopsies. In three cases the nodal involvement by CLL was demonstrated both by the presence of a predominant background of CD5/CD19/CD23+ small lymphocytes and an IgH monoclonal rearrangement revealed by PCR analysis. Conversely, in the remaining case there was neither immunohistological nor molecular evidence of lymph node involvement by CLL. In all four cases H/RS cells were Epstein-Barr virus (EBV) latent membrane protein (LMP-1) positive. These findings suggest that the presence of H/RS cells in the first three patients, who had CLL/HD nodal involvement, might be related to transformation or clonal evolution of CLL cells in H/RS cells, which is in keeping with use of the term ”CLL with Hodgkin’s transformation”. In the fourth case a de novo HD may be postulated, representing a second malignancy presumably not clonally related to CLL. In all cases a key pathogenetic role of EBV is suggested by the expression of LMP-1 in H/RS cells. Our findings indicate that the presence of typical H/RS cells in lymph node biopsies in CLL patients may reflect a heterogeneous pathogenetic background. The different clinico-pathologic settings should be taken into consideration because of their possible implications for patients’ treatment and prognosis.

Acute leukaemia in patients treated for Hodgkin's disease

Fourteen acute non‐Iymphoid leukaemias (ANIL) were identified among 947 consecutive patients with Hodgkins disease (HD) treated in five collaborating centres in Italy between January 1969 and December 1979.

Treatment of MOPP-resistant Hodgkin's disease with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)

Abstract ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) was given in monthly courses to 20 patients with Hodgkins disease resistant to MOPP. Complete responses were achieved in 10 of the 18 evaluable patients ( 55% ). Responses occurred rapidly with a median of 3 months . Nine of the 10 complete responders are presently off all therapy and remain disease-free after 9–60 months . The actuarial median survival for all patients is 38 months . Toxicity caused by ABVD was acceptable. ABVD is a useful salvage chemotherapy program for patients with Hodgkins disease resistant to MOPP.

Peripheral neuroectodermal tumor of the chest (Askin tumor) as secondary neoplasm after Hodgkin's disease: A case report

SummaryThe authors present the case of a 20-yearold woman who developed a peripheral neuroectodermal neoplasm of the thoracopulmonary region (Askin tumor) 7 years after achieving complete remission of stage-IV Hodgkins disease. The previous treatment had consisted of eight courses of alternating MOPP/ ABVD combined with involved-field 20-Gy radiotherapy. The second neoplasm appeared in a nonirradiated area of the chest wall, with erosion of the ribs as shown by sonography and computed tomography. The histological pattern was in accordance with a generic diagnosis of a malignant small cell tumor; the immunostaining positivity of the neoplastic cells for the neuron-specific enolase allowed us to make the diagnosis of a tumor with a neuroectodermal origin. Partial resection of the neoplasm and four courses of chemotherapy including adriamycin, cisplatin, and ifosfamide induced a complete remission, confirmed by surgical restaging. She is alive and well 10 months after the completion of therapy. The clinical, radiological, and microscopic features of this tumor occurring as a secondary neoplasm after Hodgkins disease are described.

Avascular osteonecrosis in patients treated for Hodgkin's disease

Abstract: The aim of this study is to assess the risk of avascular osteonecrosis (AVN) of the femoral head in patients treated for Hodgkins disease (HD), in relation to the type of treatment they have received. For this purpose, a cohort of 1391 patients treated for HD at University of Rome between 1972 and 1996 was divided into 2 groups according to their initial treatment. The first group contained 784 patients treated, at the onset of HD, either with chemotherapy (CT) containing steroids, combined in some cases with subdiaphragmatic radiotherapy (RT), or with subdiaphragmatic RT combined with CT without steroids. The second group was made up of 607 patients who had received, initially, supradiaphragmatic RT alone or supradiaphragmatic RT combined with CT without steroids. For the purpose of this study, only the 784 patients belonging to the first group were observed for the appearance of AVN, which occurred in 9 cases. The period of time which elapsed between the end of treatment and the radiological evidence of AVN ranged from 23 to 97 months, with an average of 35 months. Because the number of cases of AVN was so small, the pathogenesis of this complication could not be identified.

Bone marrow involvement at onset of Hodgkin's disease.

Bilateral trephine bone marrow biopsies of 370 patients with Hodgkins disease first seen at the Institute of Hematology, University of Rome, between 1970 and 1981, revealed tumor involvement of the bone marrow in 18 cases. The histologic type was mixed cellularity in 7 cases, lymphocytic depletion in 4 cases, nodular sclerosis in 4 cases, and lymphocytic prevalence in 1 case. Anemia with less than 10 g/dl of hemoglobin was observed in 5 patients; white blood cells were less than 4.0 × 109/liter in 2 patients; platelets were less than 12.0 × 109/liter in 1 case; a pancytopenic condition was observed in only 1 case. B symptoms were present in 14 of the 18 patients. All patients who underwent laparosplenectomy presented spleen involvement, 4 also had liver involvement. All patients were treated with chemotherapy; MOPP regimen was employed in 11 cases, ABVD in 5 patients, and PROVECIP in 1 case. Of the 13 patients evaluable for therapeutic response, 11 achieved complete remission, with a median actuarial relapse-free survival of 15 months. The actuarial survival curve showed that 50% of all patients are projected alive at 47 months with a follow-up ranging from 1 to 109 months.

Hodgkin's disease stage I and II with exclusive subdiaphragmatic presentation. The experience of the Departments of Radiation Oncology and Hematology, University "La Sapienza" of Rome.

During the period 1978 to 1994, 1054 patients with Hodgkins disease were evaluated and treated at the Departments of Radiation Oncology and Hematology, University “La Sapienza”, Rome. A total of 549 patients presented with clinical or pathological stage I and II; 37 of these had Hodgkins disease below the diaphragm (BDHD), and 512 above the diaphragm (ADHD). A comparison of patients with BDHD versus those with ADHD showed that the first group had a higher male to female ratio. A comparison of cases with stage II BDHD versus those with stage II ADHD showed that patients with BDHD were older (48 years vs 28 years), had different histologic features and a higher incidence of systemic symptoms (67% vs 33%). Stage II BDHD patients had a worse prognosis; in fact, there were significant differences in the overall survival and relapse-free-survival rates for cases with stage II BDHD versus those with stage II ADHD (overall survival, 46% vs 80%, P<0.001; relapse-free survival, 44% vs 69%, P<0.005). Stage was found to be the most important prognostic factor for BDHD cases without systemic symptoms treated with radiation therapy alone. The type of infradiaphragmatic presentation (intra-abdominal vs peripheral disease) did not influence outcome, probably due to the more aggressive therapy received by the intra-adbominal group. Treatment recommendations for BDHD cases should be tailored to the stage and the presence or absence of intra-abdominal localization. For patients with stage IA extended fields, irradiation (inverted Y) is sufficent. However, combined modality therapy should be the treatment of choice for stage II cases, particularly in the presence of intra-abdominal disease. Patients with systemic symptoms also require combined modalities.

Recurrence of Hodgkin’s Disease after 10 Years: Observation of 5 Cases

Five patients whose Hodgkins disease recurred 10 years or more after the achievement of complete remission are reported. Four out of 5 patients had shown an advanced stage at the onset of disease and therefore had received combination chemotherapy (ABVD or MOPP-like) as primary treatment. Involved-field irradiation was delivered as consolidation therapy in 1 patient only. All pathologically proven relapses occurred in a previously affected area and the histologic subtype differed from the primary subtype. The time interval between the achievement of the first complete remission and the relapse was 120, 170 and 190 months in 3, 1, and 1 patient, respectively. All 5 patients are alive in second complete remission. This paper emphasizes the risk of late relapse even after a prolonged disease-free interval for patients with Hodgkins disease. Close follow-up is therefore recommended also in this clinical setting.

Long-term results of 60 patients with pathologic stage I & IIA Hodgkin's disease treated with exclusive mantle radiation therapy

Abstract: Between January 1972 and December 1982 60 patients with pathological stage IA and IIA Hodgkins disease (HD) were submitted to Mantle irradiation only. Twenty‐five were in stage I (32.1%) and 35 in stage II (67.9%). All patients were submitted to staging laparotomy. Cases with large mediastinal mass were excluded from this series. Delivered doses were 44 Gy in involved areas, 40 Gy on the mediastinum and 36 Gy on uninvolved sites. Twenty‐four patients in stage I (96%) and 33 in stage II (94.2%) obtained complete remission. Actuarial 10‐ and 20‐yr overall (OS) rates were 86% and 79.1%, respectively. Event‐free (EFS) and relapse‐free (RFS) survival rates at 10 and 20 yr were 67.5% and 62.1%, respectively. The occurrence of disease relapse resulted in the only statistical significant prognostic factor for OS in both univariate and multivariate analysis. Distant and extranodal recurrences were significantly (P<0.01) related to a reduced OS. On multivariate analysis stage was the only determinant factor for increased RFS. Extended field RT proved to be an effective curative modality for stage I HD patients, whereas 15 out of 33 patients in stage II relapsed requiring salvage therapy. Long‐term analysis of survival and treatment‐related morbidity rates will improve our knowledge and assist the physicians to choose the therapeutic option to offer to HD patients.

Secondary acute non lymphoid leukemia in patients treated for non Hodgkin's lymphoma: no risk of therapy-related ANLL after PROVECIP schedule.

The present study was undertaken to evaluate the frequency, characteristics and actuarial risk of secondary acute non lymphoid leukemia (s-ANLL) in 141 patients treated for non Hodgkins lymphoma with different modalities. One hundred and twenty-four patients received chemotherapy according to PROVECIP protocol (9). Of these, 15 also received as induction treatment a local nodal irradiation and 33 an extended field radiotherapy. Seventeen out of 141 were treated by total body irradiation. Of these, 15 relapsed and received salvage chemotherapy. Sixteen of the 124 patients treated with PROVECIP also underwent different chemotherapeutic programs as salvage treatment. Of the entire population studied, 2 patients developed an s-ANLL, 45 and 63 months after diagnosis of NHL. The type of treatment significantly affected the occurrence of s-ANLL, since both leukemias occurred in patients treated with total body irradiation, given alone or followed by chemotherapy. The actuarial risk at 8 years was 5.24% in the whole group, whereas it greatly increased in the group of patients treated with total body irradiation (24%). Conversely, no risk was found in the group treated with PROVECIP, alone, with additional chemotherapy, or with associated local or extended field radiotherapy.