Gillian Vaughan Hudson

Relationship of histopathologic features to survival and relapse in nodular sclerosing Hodgkin's disease. A study of 1659 patients

Nodular sclerosing (NS) Hodgkins disease (HD) with extensive areas of lymphocyte depletion or with numerous anaplastic Hodgkins cells, termed Grade II NS, is associated with a poor response to initial therapy, an increased relapse rate, and decreased survival when compared with other NS variants, termed Grade I NS. The histopathologic subdivision of NS HD into Grade I and Grade II is easy to perform and provides essential prognostic information that is independent of stage. Patients with Grade II NS HD may require more aggressive initial therapy if their survival is to be improved.

The clinical outcome of 65 cases of mantle cell lymphoma initially treated with non-intensive therapy by the British National Lymphoma Investigation Group

Mantle cell lymphoma (MCL) was first described as a distinct biological entity on the basis of its association with the t(11;14)(q13;q32) resulting in over‐expression of the cyclin D1 gene. Recognition of the morphological, immunophenotypic and clinical characteristics of MCL has enabled the accurate diagnosis of this entity and appreciation of its poor prognosis. Most published series of patients with MCL have used anthracycline‐containing regimens. In contrast the British National Lymphoma Investigation (BNLI) group have treated 65 patients with MCL with non‐intensive ‘low‐grade lymphoma’ therapy. The median overall survival of 57 months and progression‐free survival of 24 months compares favourably with the more intensively treated series. Although the disease was generally more aggressive than other low‐grade lymphomas, some patients were asymptomatic and had indolent disease. When compared to 1853 patients with non‐MCL low‐grade lymphomas entered on the BNLI database, patients were found on average to be older (P = 0.02), to have more extra‐nodal disease (P < 0.00001), and a higher proportion to have a raised ESR (P = 0.02) and a low serum albumin (P = 0.002). Multivariate analysis of significant prognostic markers in all BNLI low‐grade lymphomas failed to identify MCL as an independent prognostic factor.

G-CSF after peripheral blood stem cell transplantation in lymphoma patients significantly accelerated neutrophil recovery and shortened time in hospital: results of a randomized BNLI trial.

We have undertaken a prospective randomized study in 90 patients with relapsed or resistant lymphomas to assess the value of G‐CSF (lenograstim) in the acceleration of myeloid recovery after peripheral blood stem cell transplantation (PBSCT). A common regimen of cyclophosphamide 1.5 g/m2 on day 1 and lenograstim 263 μg s.c. on days 2–10 with two aphereses on days 10 and 11 was used for stem cell mobilization. 77% of patients achieved an adequate PBSC collection in two harvests (>2 × 108 MNC/kg or >2 × 106 CD34+ cells/kg). 65 patients went on to receive high‐dose BEAM chemotherapy and engraftment data was available for 62. 34 patients had been randomized to receive lenograstim 263 μg/d s.c. and 28 to no growth factor. The median time to ANC > 0.5 × 109/l was 9 d in the lenograstim arm versus 12.5 d in the no‐lenograstim arm (P = 0.0001). This was associated with a median duration of time in hospital post PBSCT of 13 d in the lenograstim arm versus 15.5 d in the no‐lenograstim arm (P = 0.0002). Median days to platelet independence, platelet transfusions, incidence of infection and red cell transfusion were the same in both arms. These data indicate that lenograstim significantly accelerated myeloid recovery after PBSCT and shortened the duration of hospital stay.

High-dose BEAM chemotherapy with autologous haemopoietic stem cell transplantation for Hodgkin's disease is unlikely to be associated with a major increased risk of secondary MDS/AML.

SummaryHodgkin’s disease is curable in the majority of patients, although a proportion of patients are resistant to or relapse after initial therapy. High-dose therapy with autologous stem cell support has become the standard salvage therapy for patients failing chemotherapy, but there have been reports of a high incidence of myelodysplasia/acute myeloid leukaemia (MDS/AML) following such treatment. Patients who receive such therapy form a selected group, however, who have already been subjected to other leukaemogenic factors, such as treatment with alkylating agents. In order to ascertain the true risk of MDS/AML, comparison must be made with other patients subjected to the same risks but not undergoing transplantation. We report a retrospective comparative study of 4576 patients with Hodgkin’s disease from the BNLI and UCLH Hodgkin’s databases, which includes 595 patients who have received a transplant. Statistical analysis including Cox’s proportional hazards multivariate regression model with time-dependent covariates was employed. This analysis reveals that the risk of developing MDS/AML was dominated by three factors, namely quantity of prior therapy (relative risk [RR] 2.01, 95% confidence intervals [CI] 1.49–2.71, for each treatment block, P < 0.0001) and whether the patient had been exposed to MOPP (RR 3.61, 95% CI 1.64–7.95, P = 0.0009) or lomustine chemotherapy (RR 4.53, 95% CI 1.96–10.44, P = 0.001). Following adjustment for these factors in the multivariate model the relative risk associated with transplantation was 1.83 (95% CI 0.66–5.11, P = 0.25). This study provides no evidence of a significantly increased risk of MDS/AML associated with BEAM therapy and autologous transplantation in Hodgkin’s disease. Concern over MDS/AML should not mitigate against the timely use of this treatment modality.

The Clinical and Prognostic Relevance of Histopathologic Classification in Hodgkin’s Disease

Few diseases have caused such confusion or generated as much controversy as Hodgkin’s disease. The debate over this disease has centered not only on terminology (by 1933 Wallhauser1 could find 52 synonyms for this condition in the literature), but also upon the basic nature of the disease process. The view that Hodgkin’s disease was inflammatory was held by many workers. Some believed it was an atypical reaction to the Tubercle bacillus,2 others were convinced it was a malignant tumor.3, 4 Modern karyotypic and culture studies have confirmed Hodgkin’s disease to be a neoplastic process,5,9 but although many theories have been proposed,6, 9,10– 16 the precise identity of the malignant cell has remained obscure.

Outcome of secondary myeloid malignancy in Hodgkin's disease: the BNLI experience

Abstract: In Hodgkins disease where the majority of patients are long‐term survivors secondary myeloid malignancies are a well‐documented complication. The survival of those who develop secondary myelodysplasia/ acute myeloid leukaemia (MDS/AML) is historically said to be extremely poor. This study from the BNLI database of over 4900 patients with Hodgkins disease reports long‐term follow‐up of 30 patients with secondary MDS/AML. Five patients have survived at least 5 yr (1>12 yr) from the time of diagnosis of AML. These patients were significantly younger (p=0.03) than those who succumbed to this complication and each also had standard or favourable risk cytogenetics. The actuarial 5‐ and 10‐yr survival rates are 17.4% (7.7–34.9%, 95% CI) and 8.7% (1.9–31.7%, 95% CI), respectively. There is therefore a subgroup of patients who will achieve long‐term survival despite the development of secondary myeloid malignancy.