PUVA plus interferon α2b in the treatment of advanced or refractory to PUVA early stage mycosis fungoides: a case series.

BACKGROUND: The combination of PUVA with variable doses of systemically administered interferon α2b (IFN-α2b) reduces the number of PUVA treatments and the dose of IFN-α2b required to produce remission in all mycosis fungoides (MF) stages. OBJECTIVES: To evaluate the efficacy of the combination of PUVA and IFN-α2b in patients with late stage or refractory to treatment early stage MF. METHODS: The combination of PUVA three times weekly and IFN-α2b 2-5 MU three times weekly was retrospectively reviewed in 22 patients. Kaplan-Meyer method and log-rank test was used for statistical analysis. RESULTS: Twenty-two patients were analysed, seven with refractory to PUVA early stage MF, seven with tumour stage, five with erythrodermic MF and three with Sézary syndrome (SS). The overall response rate (complete or partial response) was 68%, including 10 complete responses (CR) (45%) and five partial responses (PR) (23%). Significantly, more patients of the early stage group achieved CR compared with the advanced stage group (86% vs. 27%, P=0.03). Within the advanced stage group, CR rates were 14% vs. 37% in stage IIB and III/SS patients respectively, but the difference was not statistically significant. Patients with early stage disease had a 2-year PFS of 100% vs. 27% for the advanced stage group (P<0.001). Sustained remissions (>2 years) were achieved in five out of six complete responders in the early stage group of patients. CONCLUSION: This combination of IFN-α2b and PUVA is an effective and safe treatment for refractory to treatment early stage MF patients as well as treatment-naïve advanced stage patients. Its efficacy is more pronounced in the former patient group.

Primary effusion lymphoma in two HIV-negative patients successfully treated with pleurodesis as first-line therapy.

Primary effusion lymphoma (PEL) is a rare non-Hodgkin's lymphoma (NHL) mostly occurring in HIV-positive patients. It is characterized by the development of effusion in one or more body cavities, with no tumor masses and a positive human herpes virus-8 (HHV8) status. It has a poor survival profile and no optimal treatment is yet defined. We report two HIV-negative, HHV8-positive patients with PEL of the pleural cavity who achieved a durable remission after pleurodesis with bleomycin and no systemic therapy. We also perform a review of the relevant literature regarding the clinical data, treatment, and survival of PEL in HIV-negative patients.

Rituximab monotherapy is highly effective in splenic marginal zone lymphoma.

Splenectomy has traditionally been considered as a standard first line treatment for splenic marginal zone lymphoma (SMZL) conferring a survival advantage over chemotherapy. However it carries significant complications, especially in elderly patients. The purpose of this retrospective study was to report our experience on the efficacy of Rituximab as first line treatment in 16 consecutive SMZL patients, diagnosed in our department. The diagnosis was established using standard criteria. Patients' median age was 57 years (range, 48-78). Prior to treatment initiation all patients had splenomegaly, nine had anemia, five lymphocytosis, five neutropenia and six thrombocytopenia. Rituximab was administered at a dose of 375 mg/m2/week for 6 consecutive weeks. The overall response rate was 100%. After treatment, all patients had a complete resolution of splenomegaly along with restoration of their blood counts. Eleven patients (69%) achieved a CR, three (19%) unconfirmed CR and two (12%) a PR. Among the complete responders seven patients had also a molecular remission. The median time to clinical response was 3 weeks (range, 2-6). Rituximab maintenance was given to 12 patients. Eleven of them had no evidence of disease progression after a median follow-up time of 28.5 months (range, 14-36), while two out of four patients who did not receive maintenance, relapsed 7 and 24 months after the completion of induction treatment. Median follow-up time for the entire series was 29.5 months (range, 15-81). No deaths were recorded during the follow-up period. Therapy was well tolerated. The present study demonstrates that rituximab is an effective treatment for SMZL and could be considered as a substitute or alternative to splenectomy.

Angiogenesis in Hodgkin's lymphoma: a morphometric approach in 286 patients with prognostic implications.

The significance of angiogenesis in Hodgkin's lymphoma (HL) is not well defined. The aim of this study was to evaluate various morphometric characteristics of microvessels in lymph node sections of 286 patients with HL at diagnosis and investigate their relationship with clinicopathologic parameters and prognosis. Microvessel density (MVD), total vascular area (TVA) and several size- and shape-related microvascular parameters were quantitated--after anti-CD34 immunohistochemical staining--in the region of most intense vascularization, using image analysis. An increase in microvessel caliber parameters (area, perimeter, major and minor axis length) and a decrease in MVD were noted with increasing stage. An inverse relationship was recorded between MVD and the number of involved sites (NIS) and LDH. In univariate analysis, overall disease-specific survival was adversely affected by MVD and TVA, whereas inferior failure-free survival (FFS) was associated with the presence of more flattened vessel sections. Multivariate analysis disclosed that the extent of angiogenesis (MVD/TVA), age and the NIS independently affected overall survival. Accordingly, FFS was independently linked to the shape of microvessels and albumin levels or the NIS. In conclusion, our data support the view that angiogenesis in HL provides independent prognostic information, requiring the concomitant evaluation of quantitative and qualitative aspects of microvascular network.

Breast cancer following curative chemotherapy for non-Hodgkin's lymphoma and the effect of drug resistance proteins to the final outcome. A retrospective study.

PURPOSE: To investigate the overall survival (OS) of patients developing breast cancer (BC) after curative chemotherapy for non-Hodgkin's lymphoma (NHL) and to evaluate the possible effect on the patients' outcome of the expression of drug resistance-related proteins (P-glycoprotein-Pgp, multidrug resistance-associated protein-MRP, and multidrug resistance-related vault lung resistance protein-LRP) in BC issue. STUDY GROUP: 25 female patients (median age 60 years, range 37-70) who developed BC after chemotherapy for high/intermediate grade B-cell NHL, treated with CHOP and achieving complete remission (CR). This group was further subdivided in subgroups A and B, according to the time interval between NHL and BC development ( 24 months, respectively). A matched-pair group of de novo BC patients formed the control group. BC tissue was immuno-histochemically stained for Pgp, MRP and LRP. RESULTS: The median interval between NHL diagnosis and BC development was 26 months (range 9-49). In both groups 14 patients had tumor grade II; 16 were negative for steroid receptors; 17 overexpressed c-erbB-2; 14 were stage IIIA/B, and 11 stage IV. CMF or CNF (mitoxantrone instead of doxorubicin) were given for BC. Early progression was noticed in all study group patients for which second-line chemotherapy was instituted. There was a better response for stage IV patients in the control versus the study group (p=0.07). More prolonged OS was demonstrate for patients with stage III in the control group (median 51 months) and in subgroup B (median 47 months) than in subgroup A (median 16 months; p=0.00012), as well as for patients with advanced disease (p=0.0045). Development of BC < 24 months after NHL resulted in reduced OS (p=0.017). No difference was noticed in the expression of drug resistance proteins between the study and control group or between subgroups A and B. CONCLUSION: BC developing shortly after a CR to NHL is an aggressive disease variant with minimal potential for response to conventional chemotherapy. Analysis of Pgp, MRP and LRP failed to demonstrate significant difference between the study and control group, although indications exist that drug resistance mechanisms might be part of the aggressive disease phenotype, contributing to the poor outcome.

beta(2)-microglobulin in Hodgkin's lymphoma: prognostic significance in patients treated with ABVD or equivalent regimens.

PURPOSE: Serum beta-2 microglobulin (sbeta(2)m) is an established prognostic factor for several lymphoproliferative disorders. Because its significance in Hodgkin's lymphoma (HL) is controversial, we determined sbeta(2)m levels in pretreatment serum samples of patients with HL in order to elucidate its prognostic value in this condition. PATIENTS AND METHODS: Pretreatment sbeta(2)m levels were determined in 379 HL patients who were treated with ABVD or equivalent regimens with or without radiotherapy (RT), using a radioimmunoassay (upper normal limit 2.4 mg/l). Sbeta(2)m levels were correlated with several clinical and laboratory parameters. RESULTS: Elevated sbeta(2)m levels were detected in 138/379 (36%) patients and correlated with all clinical and laboratory baseline features except gender, lung involvement and mediastinal bulk. They also correlated with serum soluble CD30 and interleukin-10 levels. The 8-year failure-free survival (FFS) was 78 -/+ 4% for patients with normal versus 65 -/+ 7% for patients with elevated sbeta(2)m levels (p=0.003). The corresponding rates among early-stage patients were 83 -/+ 53% versus 71 -/+ 9% (p=0.003), while for advanced stages they were 70 -/+ 6% versus 64 -/+ 8% (p=0.54). In multivariate analysis of the whole patient population elevation of sbeta(2)m levels was not predictive of FFS, but it was strongly predictive among early-stage patients. The 8-year overall survival (OS) rates were 91 -/+ 3% for patients with normal versus 59 -/+ 11% (p <0,0001) for patients with elevated sbeta(2)m levels, while unrelated mortality at 8 years was 1 -/+ 1% versus 27 -/+ 12% (p<0.0001). CONCLUSION: Our data suggest that sbeta(2)m levels may be a potent prognostic factor for FFS in patients with early stage HL treated with ABVD and equivalent regimens. Their effect on OS is confounded by the higher unrelated mortality in patients with elevated baseline sbeta(2)m levels, probably due to the strong association between sbeta(2)m and older age.

Breast cancer after curative chemotherapy in non-Hodgkin's lymphoma: examination of the role of drug resistance and retrospective comparison to the outcome of de novo breast cancer.

We examined the outcome of patients who developed breast cancer after curative chemotherapy (CHOP) for aggressive non-Hodgkin's lymphoma (NHL) in comparison to the outcome of a retrospectively selected matched-pair group of patients with de novo breast cancer, and evaluated the role of drug resistance-related protein (MDR, MRP, LRP) expression in breast cancer tissue. Twenty-two patients presented with breast cancer (BC) in complete remission after CHOP for NHL. The median age was 62 (49-70) years, each had high/intermediate grade B-cell NHL treated with 6 courses of CHOP, and were in complete remission. These patients were compared to a matched-pair group of de novo BC patients selected from our database over the same time period. Breast cancer tissue was stained by immunohistochemistry for drug resistance proteins LRP, MRP, and MDR. Breast cancer developed after a median of 26 (9-49) months of NHL diagnosis; breast tumor grades 1-2 were seen in 12, and grade 3 in 10 patients; 15 were negative and 7 weakly positive for estrogen and progesterone receptors. Twelve patients were stage IIIA/B, and 10 stage IV and were treated with conventional chemotherapy regimens. All progressed early in liver (n=13), brain (n=9), lung (n=6), bone (n=8), lymph nodes (n=7) and soft tissue (n=5), and received second-line chemotherapy with mitomycin-C + vinblastine or taxanes. The overall survival was 11.8 (6-26) months (p<0.01). Time from NHL to breast cancer development was 19 (14-27) months in patients with positive drug resistance proteins (group A), and 37 (26-56) months in patients with 1 or 2 positive resistance proteins (group B) (p<0.001). In patients with stage IIIA/B disease, there was no difference between the examined and control matched-pair group in median TTP, but there was in overall survival (OS) (23 vs 36 months, p=0.029). In advanced disease, there were more responders in the control vs the examined group (p=0.07). Patients in the control matched-pair group had more prolonged OS when compared to group A patients who developed BC in <24 months from NHL to BC (p=0.017). We conclude that breast cancer developing shortly after a complete response in NHL, is an aggressive disease variant with minimal potential for response to conventional chemotherapy. Analysis of drug resistance mechanisms concerning MDR, MRP and LRP indicates that most of these patients have BC that overexpress these proteins leading to the suggestion that these mechanisms might be a part of the aggressive disease phenotype and partially explain the poor outcome.

Pulmonary Balantidium coli infection in a leukemic patient.

A 59-year-old woman suffering from chronic lymphocytic leukemia developed pulmonary lesions; bronchoalveolar lavage was performed for possible systemic fungal infection. However, direct microscopic analysis revealed ciliated protozoa identified as Balantidium coli. B. coli is the only known pathogenic ciliate, and is usually associated with intestinal infection in areas associated with pig rearing. On very rare occasions the organisms may invade extra-intestinal organs, in this case the lungs of an immunocompromised patient. This case is unusual as balantidiasis is rare in Europe, the patient had no obvious contact with pigs, and there was no history of diarrhea prior to pulmonary colonization. Metronidazole was rapidly administered, and the condition improved after 24-48 hr.

Primary lung involvement in Waldenström's macroglobulinaemia: report of two cases and review of the literature.

Pulmonary involvement in Waldenström'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.

Serum interleukin-10 levels are an independent prognostic factor for patients with Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: Interleukin-10 (IL-10) is a pleiotropic cytokine which increases bcl-2 levels and protects cells from steroid or doxorubicin-induced apoptosis. Hodgkin and Reed-Sternberg (HRS) cells bear functional IL-10 receptors. Thus serum IL-10 (sIL-10) might inhibit apoptosis in HRS cells, which could occur as a result of either chemotherapy or the crippled immunoglobulin genes. DESIGN AND METHODS: We determined sIL-10 levels in 122 patients with Hodgkin's lymphoma (HL), treated with ABVD or equivalent regimens with or without radiotherapy, and correlated them with presenting clinical and laboratory features, as well as failure-free survival (FFS) and overall survival. RESULTS: Elevated sIL-10 levels ( > or = 10 pg/mL) were detected in 55 patients (45%), and were correlated with advanced stage and elevated serum b2-microglobulin levels. At 7 years FFS was 85% vs. 63% for patients with normal vs. elevated sIL-10 levels, respectively (p=0.01); overall survival was 97% vs. 73% (p=0.005). Multivariate analysis with Cox's proportional hazards model demonstrated that elevated sIL-10 levels were the strongest independent predictor of FFS, and were also associated with inferior overall survival. INTERPRETATION AND CONCLUSIONS: We conclude that sIL-10 levels are elevated in 45% of patients with HL, and are associated with inferior FFS and overall survival, independently of other established prognostic factors.

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

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 [CR] 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.

Prognostic factors in advanced stage Hodgkin's lymphoma: the significance of the number of involved anatomic sites.

BACKGROUND: Advanced Hodgkin's lymphoma (HL) is curable by conventional chemotherapy in 60--70% of patients. The pretreatment identification of a sizeable subgroup of patients with sufficiently low failure-free survival (FFS) to be eligible for investigational treatment is necessary. OBJECTIVES: To determine the prognostic significance of the number of involved sites (NIS) in patients with advanced HL and its relationship to the International Prognostic Score (IPS). METHODS: A retrospective review of patients with advanced HL, defined as Ann Arbor stage (AAS) IB, IIB, III or IV, treated with anthracycline-based regimens. The end-point was FFS. RESULTS: We identified 277 patients with a median age of 32 yr (14--78), 57% of whom were males. AAS was I in 4% of patients, II in 29%, III in 38% and IV in 29%. B-symptoms were recorded in 81%. Most patients had nodular sclerosis (64%) and mixed cellularity (26%) histology. IPS was greater-than-or-equals 3 in 44% of 242 evaluable patients. The NIS was greater-than-or-equals 5 in 32% of the patients and 20% of all patients had both greater-than-or-equals 5 involved sites and IPS greater-than-or-equals 3. The 10-yr FFS was 67%, being 76% vs. 50% for patients with less-than-or-equals 4 vs. greater-than-or-equals 5 involved sites (P < 0.0001). The NIS (greater-than-or-equal 5), AAS IV and anemia were independent predictors of FFS in multivariate analysis. The NIS remained significant along with IPS, when the latter was included in the analysis. Patients with greater-than-or-equals 5 involved sites and IPS greater-than-or-equals 3 had 10-yr FFS overall, and relapse-free survival of 41%, 45% and 49%, respectively. CONCLUSIONS: The NIS was associated with FFS in advanced HL, was independent of IPS, and led to the identification of a sizeable subgroup of patients with 10-yr FFS of approximately 40%. This factor should be evaluated during the development of prognostic systems.

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 3 yr period, lasting 12 weeks each, at a final dose of 30 mg 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.

EBVD combination chemotherapy plus low dose involved field radiation is a highly effective treatment modality for early stage Hodgkin's disease.

To evaluate the efficacy of EBVD combination chemotherapy followed by low dose (LD) involved field (IF) radiation therapy (RT) in patients with clinical stage (CS) I-IIA Hodgkin's disease (HD), we analyzed 148 patients treated in our Unit from March 1988 to November 1995. EBVD consisted of Epirubicine 40 mg/m2, Bleomycin 10 mg/m2, Vinblastine 6 mg/m2 and Dacarbazine 300 mg. All drugs were administered i.v. at days 1 and 15, every 4 weeks, for a total of 4-6 cycles. LDIF RT (24-32 Gy) was scheduled for patients with complete response (CR) or >90% reduction of tumor load, after EBVD. Patients with stable or progressive disease (SD, PD) after EBVDx3 or poor compliance to the regimen received mantle or inverted Y RT at standard dose. The median follow-up of patients currently alive was 71.5 months. 129 patients achieved a CR after EBVD and 10 a >90% reduction of tumor load, for a post-CT response rate of 94%. Eight patients had SD after EBVDx3 and one had a partial response with poor compliance. All 9 patients received mantle or inverted Y RT and 8/9 achieved a CR. Nine patients relapsed at a median of 7 months from the end of treatment. At 10 years, FFS was 90% and overall survival 95%. Six patients have died so far; 5 of HD and one of stroke. One patient developed a diffuse large cell lymphoma 48 months after the diagnosis of HD. We conclude that EBVD followed by LDIF RT is a highly effective regimen for patients with CS I-IIA HD. Longer follow up is required to assess the risk of secondary malignancies, especially solid tumors.

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.

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 s.c. 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 s.c./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, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma, including Waldenström's macroglobulinemia: a clinical, morphologic, and biologic spectrum of similar disorders.

Among small lymphocyte cell disorders, B-chronic lymphocytic leukemia (B-CLL), small lymphocytic lymphoma (SLL), and lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/MW) are included. B-CLL patients always have blood and bone marrow (BM) involvement by a CD5+ B lymphocyte. They frequently present with lymphadenopathy and/or hepatosplenomegaly, although in a considerable number of patients, no abnormal physical findings are found. They are prone to develop hypogammaglobulinemia, autoimmune hemolysis, or autoimmune thrombocytopenia. The typical immunophenotype of the malignant cell is CD5+, surface immunoglobulin (slg)+ (weak), CD23+, CD79b-, and FMC7-. Trisomy 12 and 13q deletions are frequent chromosomal abnormalities. The bcl-2 protein is usually overexpressed. SLL patients present with lymphadenopathy, usually generalized. Lymphocytosis is by definition absent and BM involvement, usually nodular, is found in 25% to 50% of patients. The lymph node lymphocytes are CD5+ and have a similar immunophenotype with CLL, but frequently express the LFA-1 adhesion molecule. Patients are at low risk to develop hypogammaglobulinemia, autoimmune hemolysis, or autoimmune thrombocytopenia. LPL/MW patients may present either with an accidental discovery of IgM gammopathy, symptoms related to paraproteinemia, or lymphadenopathy and/or splenomegaly. The BM is frequently involved and a leukemic picture may be found. A monoclonal gammopathy of IgM class is by definition present in MW and is frequently accompanied by hypogammaglobulinemia. Immunophenotypic studies usually reveal a CD5-, slg+ (moderate), cytoplasmic immunoglobulin (clg)+, FMC7+, and CD38+ cell. A significant proportion of cases carry the translocation t(9;14)(p13;q32) involving the PAX-5 gene. All of these disorders may potentially undergo transformation to large-cell lymphoma or Richter's syndrome. Prognostic factors have been extensively studied in B-CLL, but more studies are needed for SLL and LPL/MW. These entities should be differentiated from other B-chronic small lymphocyte cell disorders, particularly when the latter are leukemic.

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 (cICAM-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, cICAM-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). cICAM-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 cICAM-1 with lactate dehydrogenase (LDH) (r(s) = 0.532, p = 0.049), and a significant increase in cICAM-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 cICAM-1 (r = -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 cICAM-1 in subgroup B+C (r(s) = -0.659 [p = 0.014] and r = 0.679 [p = 0.011], respectively) was found. CONCLUSIONS: The abovementioned findings and good performance characteristics of TN and cICAM-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.