Campath-1H in B-chronic lymphocytic leukemia: report on a patient treated thrice in a 3 year period

Monoclonal antibody (mAb) therapy is a novel alternative treatment for lymphoid malignancies. in this report we present a 55-year-old patient with B-chronic lymphocytic leukemia, who was initially treated with chlorambucil p.o. and subsequently with cyclophosphamide iv with poor response. Then Campath-1H mAb was administered, He received three cycles of Campath-1H, over a 3yr period, lasting 12 weeks each, at a final dose of 30mg weekly, on an outpatient basis. After each cycle of Campath-1H administration there was a significant decrease of the size of the palpable lymph nodes, spleen and liver. Restoration of the blood lymphocyte count to normal and a significant decrease of the bone marrow lymphocytic infiltration was observed at the end of each cycle. Therefore, a major clinical response was obtained after all cycles. Campath-1H administration was well tolerated without causing any serious toxicity

EFFECTIVE TREATMENT OF DISEASE-RELATED ANEMIA IN B-CHRONIC LYMPHOCYTIC-LEUKEMIA PATIENTS WITH RECOMBINANT-HUMAN-ERYTHROPOIETIN

Nine B-chronic lymphocytic leukaemia (B-CLL) patients suffering from anaemia, due to no obvious cause except their disease, were treated with recombinant human erythropoietin (r-HuEPO). The treatment protocol provided a closed label phase of 3 months duration, during which the patients received r-HuEPO or placebo in a ratio of 2:1, followed by an open label phase, also of 3 months duration, during which r-KuEPO was administered to all patients three times a week s.c. r-HuEPO was given at a dose of 150 U/kg of body weight with an escalation of 50 U/kg up to a maximum of 300 U/kg three times a week. Complete response was achieved in 5/9 (55%) patients and partial response in 3/9 (33%). The response obtained was independent of the pretreatment serum EPO levels, the duration of anaemia, the concomitant administration of chemotherapy, the presence of splenomegaly, or the degree of bone marrow infiltration by lymphocytes. It appears that r-HuEPO is very effective in reversing the disease-related anaemia of B-CLL patients

Correction of disease related anaemia of B-chronic lymphoproliferative disorders by recombinant human erythropoietin: Maintenance is necessary to sustain response

Thirty three B-chronic lymphoproliferative disorder (B-CLD) patients [22 with B-chronic lymphocytic leukemia (B-CLL), 5 with small lymphocytic lymphoma (SLL) and 6 with lymphoplasmacytic lymphoma (LPL)] with anaemia (Ht <32%) of no other cause but their disease, received recombinant human erythropoietin (r-HuEPO). The treatment protocol provided r-HuEPO in a dose of 150 U/kg sc. thrice weekly for 3 mo. After 1.5 mo of r-HuEPO administration, if response was not satisfactory, r-HuEPO dose escalation was utilised by giving incremental doses of 50 U/kg more than the previous dose up to a maximum dose of 300 U/kg tiw. After maximal response, half of the responding patients discontinued therapy, while the other half received maintenance therapy at a dose of 150 U/kg sc./w. Oral iron was given throughout the study. Pretreatment EPO levels were determined in all patients. A complete response (CR) was defined when Ht was >38% and a partial response (PR) when there was an increase of the Ht >6% from the initial value was achieved. Sixteen of the 22 B-CLL patients had Rai stage III disease and 6 stage IV, with a median duration of anaemia 27 months (6-38); twelve of them were receiving chlorambucil while the rest were on no treatment. Of the SLL and LPL group, 4 patients had Ann Arbor stage III disease and 7 stage IV with a median duration of anaemia 24 months (5-36); 8 patients were on chlorambucil. Complete response was achieved in 50% of the B-CLL group and 54% of the SLL and LPL group, with an overall response rate of 77 and 81% respectively. All patients on maintenance therapy had a continuous response, while all patients. in whom rHuEPO was discontinued, relapsed. No correlation was found between patients: with low or high pretreatment serum EPO levels; those receiving concomitant therapy or not; those with B-symptoms or not; those with a non-diffuse or diffuse bone marrow infiltration pattern: and with splenomegaly or not. Life quality was significantly improved and no major side effects were encountered. We conclude from our study that r-HuEPO is very effective in correcting disease-related anaemia in B-CLD, resulting in down-staging of Rai stage III patients and that maintenance therapy is necessary. Whether the correction of anaemia improves patients’ overall survival, still remains to be seen

B-chronic lymphocytic leukemia: Practical aspects

B-CLL is the most common adult leukemia in the Western world. It is a neoplasia of mature looking B-monoclonal lymphocytes co-expressing the CD5 antigen (involving the blood, the bone marrow, the lymph nodes and related organs). Much new information about the nature of the neoplastic cells, including chromosomal and molecular changes as well as mechanisms participating in the survival of the leukemic clone have been published recently, in an attempt to elucidate the biology of the disease and identify prognostic subgroups. For the time being, clinical stage based on Rai and Binet staging systems remains the strongest predictor of prognosis and patients’ survival, and therefore it affects treatment decisions. In the early stages treatment may be delayed until progression. When treatment is necessary according to well-established criteria, there are nowadays many different options. Chlorambucil has been the standard regimen for many years. During the last decade novel modalities have been tried with the emphasis on fludarabine and 2-chlorodeoxyadenosine and their combinations with other drugs. Such an approach offers greater probability of a durable complete remission but no effect on overall survival has been clearly proven so far. Other modalities, included in the therapeutic armamentarium, are monoclonal antibodies, stem cell transplantation (autologous or allogeneic) and new experimental drugs. Supportive care is an important part of patient management and it involves restoring hypogammaglobulinemia and disease-related anemia by polyvalent immunoglobulin administration and erythropoietin respectively. Copyright (C) 2002 John Wiley Sons, Ltd

Imaging of primary central nervous system lymphoma before and after radiotherapy

The imaging studies of seven patients (two of whom had acquired immunodeficiency syndrome) with histologically proven primary lymphoma of the central nervous system (PCNSL) were reviewed. Computed tomography (CT) and magnetic resonance imaging (MRI) scans were taken prior to and following radiotherapy. After radiotherapy, except in one case, all tumors rapidly decreased in size either partially or completely. The imaging features on MRI scans are not pathognomonic since intracerebral infections or gliomatosis cerebri may give similar findings. However, on T2-weighted images, homogeneous, slightly high-signal to isointense masses deep within the brain and in close proximity to the corpus callosum may give characteristic appearances. MRI findings assist in the differential diagnosis between PCNSL and toxoplasmosis, metastatic disease, gliomas and infarcts, especially if the tumor is situated in the brain stem and the posterior fossa. It is also useful in the follow-up of patients after radiotherapy in order to make management decisions related to adjuvant chemotherapy administration

Campath-1H (anti-CD52) monoclonal antibody therapy in lymphoproliferative disorders - A review

Campath-1H is a humanized monoclonal antibody targeted against the CDw52 membrane antigen of lymphocytes, which causes complement and antibody-dependent cell-mediated cytotoxicity. Campath-1H has been used in B-chronic lymphocytic leukemia (B-CLL), T-prolymphocytic leukemia (T-PLL), and low-grade non-Hodgkin’s lymphoma (LGNHL). Campath-1H is administered intravenously thrice weekly for up to 12 wk, at an initial dose of 3 mg, escalated to 10 and 30 mg. The responses (complete FCR] and partial [PR]) obtained in untreated B-CLL patients are of the order of 90%. In previously treated B-CLL patients, responses are of the order of approximately 40%, with 2-4% CRs. Responses are more prominent in the blood and bone marrow compared to the lymph nodes. The median duration of response is 9-12 mo. Because of the antibody’s higher activity on circulating lymphocytes, it has been used for in vivo purging of residual disease in B-CLL, followed by autologous stem-cell transplantation. In heavily pretreated advanced stage LGNHL, response is achieved only in 14% of cases with B-phenotype; a 50% response rate is noted in mycosis fungoides. In T-PLL, the CR rate is approximately 60%. Promising results have been reported in a small number of patients with refractory autoimmune thrombocytopenia of lymphoproliferative disorders. The main complications of Campath-1H treatment are caused by tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 release, usually during the first intravenous infusion, and include fever, rigor, nausea, vomiting, and hypotension responsive to steroids. These side effects are usually less severe with subsequent infusions and can be prevented by paracetamol and antihistamines. Immunosupression resulting from normal B- and T-lymphocyte depletion is frequent, resulting in an increased risk for opportunistic infections. More clinical trials in a larger number of patients are necessary to determine the exact role and indications of Campath-1H in lymphoproliferative disorders

Serum levels of tetranectin, intercellular adhesion molecule-1 and interleukin-10 in B-chronic lymphocytic leukemia

Background and objective: The fibrinolytic regulator tetranectin (TN), in association with the circulating intercellular adhesive molecule-1 (clCAM-1) and interleukin-10 (IL-10), may be involved in the metastatic cascade of B-chronic lymphocytic leukemia (B-CLL). Our aim was to investigate the potential usefulness of these molecules as prognostic markers in B-CLL. Design and methods: Therefore, TN, clCAM-1, and IL-10 were assessed (ELISA) in the serum of 53 B-CLL patients, classified in Binet A, B, and C stages in comparison with those in 45 healthy subjects (HS). Results: TN was significantly lower in B-CLL patients than in HS (9.63 [8.75-11.51] mg/L, 13.75 [12.56-14.64] ng/mL, respectively. p < 10(-5)), being lower (p = 0.05) in B and C stage patients (subgroup B+C) than in A stage ones (subgroup A). clCAM-1 levels were significantly higher in B-CLL patients than in HS (475.86 [355.86-593.79] ng/mL vs. 225.62 [118.49-312.83] ng/mL, respectively, p = 10-5) with a tendency for higher levels in subgroup B+C than in subgroup A. A significant correlation of clCAM-1 with lactate dehydrogenase (LDH) (r(s) = 0.532, p = 0.049), and a significant increase in clCAM-1 in B-CLL with diffuse bone marrow infiltration (BMI) compared to that in B-CLL with nondiffuse BMI (624.48 [557.24-726.55] ng/mL vs. 480.34 [368.96-590.34] ng/mL, respectively, p = 0.0172) were found. A significant negative correlation between TN and clCAM-1 (r(s) = -0.5017, p = 0.0001) was observed. IL-10 was detected in all B-CLL patients and in no HS (7.37 [5.30-10.55] pg/mL), being higher (p = 0.0153) in C than in A stage patients. A significant correlation of IL-10 with TN and clCAM-1 in subgroup B+C (r(s) = -0.659 [p = 0.014] and r(s) = 0.679 [p = 0.011], respectively) was found. Conclusions: The abovementioned findings and good performance characteristics of TN and clCAM-1 in B-CLL suggest the potential usefulness of these adhesive/recognition molecules as prognostic markers in B-CLL. The implication of these molecules along with IL-10 in the disease process deserves further study. Copyright (C) 1999 The Canadian Society of Clinical Chemists

Primary lung involvement in Waldenstrom's macroglobulinaemia - Report of two cases and review of the literature

Pulmonary involvement in Waldenstrom’s macroglobulinaemia (WM) occurs in 3-5% of cases, but lung involvement without bone marrow infiltration is extremely rare, We report 2 patients who presented with bilateral consolidations on chest X-ray and non-specific symptoms and were treated for a long period of time for pulmonary infections until the diagnosis was made by open lung biopsy, Both patients presented high monoclonal IgM in the serum and one also had blood lymphoplasmacytosis. Trephine bone biopsy and bone marrow smears were normal and there was no other site of involvement. Along with the presentation of our patients, we review the literature, discuss some of the possible underlying mechanisms and raise the attention of clinicians to this rare manifestation of the disease. Copyright (C) 2001 S. Karger AG, Basel

Primary non-Hodgkin's lymphoma of the gall bladder

Primary non-Hodgkin lymphoma of the gallbladder is a very rare location of extranodal non-Hodgkin lymphomas. A patient with a primary non-Hodgkin lymphoma of the gallbladder is reported and in addition, the English literature is reviewed. Clinical presentation, diagnostic evaluation, histopathologic findings, treatment modalities and prognosis of primary gallbladder lymphomas reported up to date are reviewed and discussed. Our patient was diagnosed as a T-cell lymphoblastic lymphoma, after cholecystectomy, and had no evidence of disease elsewhere. She was treated with combination chemotherapy and complete remission was achieved. She remains free of disease 9 years later. Review of the literature over a 30-year period revealed only 12 cases of well-documented primary non-Hodgkin lymphoma involvement of the gallbladder, including the present case. Patients present clinically with symptoms and signs indicating either biliary tract pathology or a gastrointestinal tumor. Diagnostic investigation included ultrasound of the upper abdomen, computed tomography of the abdomen and pelvis, oral cholecystography, percutaneous cholangiography and endoscopic retrograde cholangiopangreatography. Preoperative diagnosis was established in none of the patients. Treatment modalities included surgery and postoperative chemotherapy and irradiation. The prognosis is overall poor and only 2 patients are alive after 1 and 9 years respectively, the latter being our case. Here we document the first reported case of a patient with primary T-cell lymphoblastic non-Hodgkin lymphoma of the gallbladder. Review of the literature shows the existence of non-Hodgkin lymphoma of the gallbladder, its rarity and its general dismal prognosis