Favourable response to therapy with the anti-CD20 monoclonal antibody rituximab in primary chronic cold agglutinin disease.

The 'primary' form of chronic cold agglutinin disease is a clonal B-cell lymphoproliferative disorder that is notoriously difficult to treat with drugs, including corticosteroids, alkylating agents, alpha-interferon and purine analogues. We performed a small, open, uncontrolled, prospective study to evaluate the effect of therapy with the monoclonal anti-CD20 antibody rituximab. Six patients with clonal CD20(+)kappa(+) B-cell proliferation received seven courses of rituximab 375 mg/m(2), d 1, 8, 15, and 22. One patient achieved a complete response. Four partial responses were observed, including a response to re-treatment in one patient. Two patients were categorized as non-responders. Haemoglobin levels increased by a median of 4.1 g/dl in the total group and 4.7 g/dl in the responders, who also experienced a substantial improvement of clinical symptoms. The treatment was well tolerated. We discuss the effect of rituximab therapy compared with other treatment options, and try to explain why two individual patients did not respond. Despite the small numbers, the results are very encouraging. Further studies of rituximab therapy for chronic cold agglutinin disease are warranted.

Stage I high-grade non-Hodgkin's lymphoma.

We report long-term survival and prognostic factors in 252 patients with stage I high-grade lymphoma. Median patient age was 64 years and 49% of patients had extranodal lymphoma. Premenopausal women had less risk of extranodal lymphoma than older women or males (p < 0.002). Disease specific 5 and 15 years' survival in patients < 64 years was 83% and 76%, respectively; compared to 54% and 46% in patients > 64 years of age. Age, non-centroblastic histology, B-symptoms, and increased serum lactate dehydrogenase (LDH) were independently negative prognostic factors (p < 0.01), while extranodal, testicular, or bulky ( > 6 cm) lymphoma presentation were of no prognostic significance. A radiation dose of 40 Gy in 2 Gy fractions to the primary site prevented in-field relapse in 159 of 173 irradiated patients (92%) and only three of 173 patients (1.7%) had local relapse in the absence of systemic dissemination.

Prognostic value of lymphoma-specific S-phase fraction compared with that of other cell proliferation markers.

The proliferation-associated antigens Ki67 (immunohistochemistry) and proliferative cell nuclear antigen (PCNA) (immunohistochemistry and immunoblotting) were analysed together with DNA synthesis (3H-thymidine incorporation) and cell-cycle distribution (tumour-specific S-phase fraction determined by flow cytometry) in lymph node suspensions from 63 patients with newly diagnosed B-Cell non-Hodgkin's lymphomas. Details of clinical parameters, treatment and patient outcome were available for all patients, and retrospectively analysed. Of the proliferation-associated parameters, only high S-phase fraction (p < 0.00001) and high PCNA expression by immunoblotting (p = 0.012) were predictive of a poor prognosis. Of the conventional parameters, high-grade malignancy, high International Prognostic Index (IPI) score, bulky disease and presence of B symptoms predicted a patient for poor survival. High S-phase fraction was predictive of a short survival for the low-grade lymphomas analysed separately (p < 0.00001), as well as for patients treated with an Adriamycin- and a non-Adriamycin-containing regimen (p < 0.005 for both groups). In a multivariate analysis, S-phase fraction (p = 0.00006), IPI score (p = 0.015) and B symptoms (p = 0.017) had independent prognostic values, but not histological grade.

Bone-marrow MR imaging before and after autologous marrow transplantation in lymphoma patients without known bone-marrow involvement.

PURPOSE: To study lumbar bone marrow by means of MR imaging before and after bone-marrow transplantation in lymphoma patients. Particular emphasis was paid to heterogeneity and to focal manifestations, i.e. appearances that could simulate tumor. MATERIAL AND METHODS: Twenty-two patients who were disease-free for a minimum of 30 months after transplantation were studied in 107 MR examinations. Two radiologists visually evaluated coronal T1-weighted and short inversion time inversion-recovery (STIR) images. RESULTS: T1-weighted images demonstrated a more heterogeneous marrow after transplantation than before it. Sharply defined focal low signal intensity areas appeared on this sequence in 5 (23%) of the 22 patients at between 21 and 60 weeks after transplantation. The mean age of these 5 patients was 48.4 years (range 42-54 years). The difference in age between these 5 patients and the remaining 17 patients, who had a mean age of 33.4 years (range 14-51 years), was statistically significant (p < 0.01, Student's t-test, 2-sided test). CONCLUSION: Sharply defined focal low signal intensity areas may be seen on T1-weighted images of bone marrow in patients who are in complete remission after transplantation, particularly in those aged over 40-45 years.

Hodgkin's disease in a national and hospital population: trends over 20 years.

The aim of the study was to investigate the incidence rate and time trends in a national registry population of Hodgkin's disease (HD) and the effects of selection in a hospital population. A national registry population of all HD patients from Norway and a hospital population of HD patients treated at the Norwegian Radium Hospital (NRH) were studied retrospectively from 1971 to 1993. The incidence of non-Hodgkin's lymphomas (NHL) in Norway increased steadily from 1961 in contrast to a stable incidence pattern for HD before 1980 and a decreasing incidence since 1980. Due to improved diagnostic tools after 1980, an increasing proportion of patients previously diagnosed as lymphocyte depleted and unclassified HD were classified as NHL. As these histologies are dominant in older patients, the incidence of older patients with HD and the total population of HD have decreased since 1980. As a result, the proportion of young adults with a favourable histology has increased. These changes may partly explain the increased patient survival observed both in the national and the hospital population. The hospital population comprised 92% of patients aged 15-39 years, 80% of patients aged 40-59 years and 53% of patients aged > 60 years in the national population. The selection of younger patients in the hospital material may explain a higher survival rate as compared with the national population.

[High-dose therapy with autologous stem cell support in malignant lymphoma and breast cancer. Experiences with hematopoietic stem cells isolate from blood]. / Høydosebehandling med autolog stamcellestøtte ved malignt lymfom og cancer mammae. Erfaring med hematopoetiske stamceller høstet fra blod.

Since 1994, 17 breast cancer patients and 16 lymphoma patients have been treated at the Norwegian Radium Hospital with high-dose therapy supported by autologous peripheral progenitor cells. All the patients were given granulocyte colony stimulating factor in the recovery phase after cytotoxic treatment in order to mobilize and harvest peripheral progenitor cells. Aphareses were successful in all patients and the mean number of CD34 cells reinfused per kilo body weight was 7.05 x 10(6) for the lymphoma patients and 11.1 x 10(6) for the breast cancer patients. The mean time to recover > or = 0.5 x 10(9)/l granulocytes and > or = 20 x 10(9)/l platelets after reinfusion of stem cells was 10 days and 11.7 days respectively for the lymphoma patients, while the breast cancer patients engrafted at day 8.6 and day 9.3. No severe treatment-related complications were observed.

Clinical stage I and II Hodgkin's disease: long-term results of therapy without laparotomy. Experience at one institution.

BACKGROUND: We concluded a program in which we administered radiotherapy only to clinical stages I and II Hodgkin's disease patients at standard risk, with the addition of 4 cycles of combination chemotherapy before radiotherapy for high-risk patients. PATIENTS AND METHODS: From 1980 to 1991, 313 patients with clinical stages I or II Hodgkin's disease underwent treatment in our hospital. Fifty percent of the patients in groups previously identified as being at high risk for relapse received 4 cycles of combination chemotherapy before radiotherapy. The remaining half of the patients received radiotherapy only. RESULTS: Low- and high-risk patients aged 15-59 years had, respectively, complete remission (CR) rates of 97% and 94%, 5-year survivals of 95% and 91%, and 5-year freedom from relapse (FFR) rates of 78% and 89%. Older low- and high-risk groups had CR rates of 97% and 93%, 5-year survivals of 60% and 56% and 5-year FFR of 77% and 93%, respectively. CONCLUSION: Here we present our favorable results after treating standard-risk patients with clinical stages I and II Hodgkin's disease with radiotherapy only. With the addition of chemotherapy, the rate of relapse in the high-risk patients was reduced below that of the standard-risk patients. Overall survival was the same for the high- and standard-risk patients.

[Human T-cell lymphotrophic virus type I and T-cell lymphoma]. / Humant T-cellelymfotropt virus type I og T-cellelymfom.

Human T-cell lymphotropic virus type I is an oncogenic retrovirus, endemic in Southwestern Japan, the Caribbean, some parts of Africa and Central and South America. The virus is etiologically associated with adult T-cell leukemia/lymphoma and a myelopathy called tropical spastic paraparesis or HTLV-I associated myelopathy. Transmission of the virus is almost identical to that of HIV. The latency period before onset of clinical symptoms can last from a few years (tropical spastic paraparesis) up to several decades (adult T-cell leukemia/lymphoma). Four different clinicopathological subtypes of the T-cell neoplasia are known, and in this article we describe two patients with the subtype lymphoma.

Prognostic variables and results of salvage treatment in Hodgkin's disease.

Treatment results and prognostic variables were studied in 549 adult patients with Hodgkin's disease after first-line and salvage treatment. After first-line treatment, 479 out of 549 patients (87%) achieved complete remission (CR). During a mean observation time of 74 months, 99 patients (21%) relapsed. Sixty-nine patients (70% of relapsed patients) achieved a second CR. Variables predicting poor response (< CR) and shortened survival after first-line treatment were advanced disease, B-symptoms and age >60 years. In relapsing patients, age >60 years, relapse within 12 months and non-CR after relapse treatment predicted a poor prognosis, and none of these patients were alive after 10 years. Localized disease at diagnosis and relapse, and relapse later than 24 months predicted a good prognosis with 10-year survival after relapse of 68% and 57%, respectively. Patients with a second relapse had 5-year survival of 28% and 10-year survival of 14%. Based on the prognostic variables at first-line treatment and at relapse, selection of patients to more intensive treatment is discussed.

Small cell pleomorphic T-cell lymphoma presenting with cutaneous vasculitis.

The association between cutaneous vasculitis and lymphoproliferative disease has been increasingly recognized. We report a female patient who presented with cutaneous vasculitis which was due to a small cell pleomorphic T-cell lymphoma. In spite of aggressive therapy, she died two years after onset of disease. The clinical picture of vasculitis associated with lympho-proliferative disease is addressed with particular emphasis on symptoms and signs suggesting malignancy rather than vasculitis appearing in concert with well-defined connective tissue disorders.

A 10-year experience with splenectomy in patients with malignant non-Hodgkin's lymphoma at the Norwegian Radium Hospital.

BACKGROUND: Splenectomy is a major surgical intervention that has many implications for patients with malignant non-Hodgkin's lymphoma. As debated during the last few decades, the therapeutic benefit must outweigh the surgical risk and the loss of cellular immunity. A more liberal attitude toward splenectomy developed during the years 1980-1990 at the Norwegian Radium Hospital, as illustrated by the higher number of operations performed in the last 5 years (21 patients) compared to the first 5 years (14 patients). METHODS: A 10-year retrospective review of the effects and side effects of splenectomy in 35 patients with malignant non-Hodgkin's lymphoma was performed, based on information obtained from the patient files at the authors' institution. RESULTS: Clinical Stage IV disease was found in 29 patients (83%), and B symptoms in 15 patients (43%). At diagnosis, 26 patients (74%) had splenomegaly, and 8 patients (23%) had primary splenic lymphoma. The surgical mortality was 2.9%, and the morbidity was 37%. Infection was the most common complication, occurring in seven patients (20%). Pneumococcal vaccination had been performed in 13 patients, and the frequency of septicemia and pneumonia tended to be higher during follow-up in unvaccinated patients (not significant). Blood counts returned to normal during the first postoperative month in 18 of 25 patients (72%) who had cytopenia. After splenectomy, a durable remission was achieved in five patients (14%) who did not receive subsequent treatment. CONCLUSIONS: Splenectomy has the potential to relieve local symptoms, correct cytopenias, and modify the disease course in patients with malignant non-Hodgkin's lymphomas, even in advanced stages, at the cost of an acceptable operative risk.

Detection of bone marrow metastases in small cell lung cancer patients. Comparison of immunologic and morphologic methods.

An immunocytochemical method, involving four monoclonal antibodies (MAbs) previously selected for their specific binding to small cell lung cancer (SCLC) cells in human bone marrow, was used for detection of bone marrow metastases in 81 patients with diagnosed SCLC. This procedure was compared with two routine morphologic methods with regard to diagnostic efficiency and sensitivity. Bone marrow involvement was found in 26 patients (32%), one of which had limited disease according to conventional clinical criteria. Eight of the positive cases were exclusively diagnosed by immunocytochemistry, whereas the histologic and cytologic methods separately identified two patients each. Immunocytochemistry had a detection level of tumor cells in the mononuclear cell fraction of approximately 1-2%, whereas no patients with less than 10% immunocytologically detectable tumor cells were diagnosed by cytomorphologic examination of bone marrow aspirates. Evidence was obtained that the diagnostic efficiency of any method increased with the number of samples examined. Of the four MAbs used, the anti-NCAM antibody, MOC-1, labeled tumor cells in all immunologically positive patients, and in all but one of these patients all cytologically confirmed tumor cells were stained. The antibodies MOC-31, which recognize a cluster-2 antigen, and NrLu10 bound nearly all tumor cells in most cases, whereas MLuC1 only diagnosed tumor cells in a fraction of the patients. The results show that the immunocytochemical application of these antibodies is superior to morphologic techniques in detecting SCLC bone marrow metastases. Further use of the method might provide prognostically and therapeutically useful information.

Bone marrow examination in Hodgkin's disease.

Bone marrow aspiration and biopsy was performed as part of routine staging in 425 patients with primary Hodgkin's disease. Only seven patients were found to have bone marrow disease by biopsy and only four by aspiration. All these patients had B symptoms and stage III or IV before bone marrow examination. Bone marrow infiltration did not influence treatment decision and there was no association between bone marrow findings and outcome of the disease.

Karyotyping of a hematologic neoplasia developing shortly after treatment for cerebral extragonadal germ cell tumor.

Hematologic malignancies may be associated with mediastinal extragonadal germ cell tumors. It may be that the hematologic malignancy is a part of the natural history of the teratoma, one germ cell tumor line being able to differentiate into hematological cells, or the hematologic malignancy is related to the treatment, or the two malignancies develop independently. Cytogenetic analysis of bone marrow from a patient with a germ cell tumor in the brain and the almost simultaneous appearance of a hematologic neoplasia showed a rearranged karyotype in that all 15 analyzed cells had the same karyotype: 50,XY, +X, +del(1)(p21), +10, +11, -12, +der(12)t(12;?)(q?;?). Our findings were consistent with the interpretation that the hematologic malignancy was derived from the germ cell tumor.

[Non-Hodgkin's lymphoma in the gastrointestinal tract]. / Non-Hodgkins lymfom i gastrointestinaltractus.

The gastrointestinal tract is the predominant site of extranodal non-Hodgkin's lymphoma. We present a summary of our recommendations as regards treatment. To avoid serious complications, such as perforation and/or bleeding, surgical resection should be considered before chemotherapy or radiation therapy. The laparotomy gives an opportunity to perform an exact staging procedure, including biopsy from the primary site and the lymph nodes. We recommend that gastrointestinal malignant lymphomas should be referred to medical centers with special competence in this field.

[Visceral leishmaniasis (kala-azar)]. / Visceral leishmaniasis (kala azar).

Visceral leishmaniasis is a serious zoonosis which has very rarely been diagnosed in Norway. We report a case of visceral leishmaniasis in a Norwegian patient, and present an up-to-date review of the disease. We conclude that this disease should be considered even in Scandinavian patients if the appropriate symptoms and signs are present and there has been possibility of exposure. Simple blood tests and serum electrophoresis are of considerable value. If possible, the protozoa should be demonstrated by microscopy of bone marrow aspirate. We also discuss the identification of the parasites in bone marrow biopsy, which should be performed in pancytopenic patients. The diagnosis should be confirmed by culture or a serological test.

[Diagnosis and treatment of solitary plasmacytoma]. / Diagnostikk og behandling av solitaere plasmacytomer.

Solitary plasmacytomas are rare tumours. We report our experience from 25 solitary osseous and 18 solitary extramedullary plasmacytomas. 41 patients were given high voltage radiotherapy, usually 40 Gy in 20 fractions. Two patients with extramedullary plasmacytoma developed generalized disease, while ten patients with osseous plasmacytoma developed myelomatosis. Extramedullary plasmacytomas are usually cured by adequate local treatment, while in solitary osseous plasmacytomas the prognosis is more dubious.

Extramedullary plasmacytomas and solitary plasma cell tumours of bone.

We describe clinical features and treatment results in 25 patients with solitary osseous (SOP) and 18 patients with solitary extramedullary plasmacytoma (EMP). 41 patients were treated with high-voltage radiotherapy, median 40 Gy in 20 fractions. Surgery was part of the treatment in 21 and chemotherapy in 5 patients. The median age in both groups was 56 years, with a preponderance of males. Myelomatosis developed in 10 SOP and 2 EMP patients, and this development did not correlate with the presence or absence of an M-component at the time of diagnosis of plasmacytoma. The estimated 5- and 10-y survival was 87% and 76% without a statistical difference between SOP and EMP groups. The patients in the SOP group usually died from myelomatosis while EMP patients died from other causes.