CD5-positive Diffuse Large B-cell Research Articles

Ocular involvement as first sign of isolated CNS relapse in diffuse large B-cell lymphoma

A 52-year-old man was diagnosed with stage IVB nonHodgkin lymphoma of diffuse large B-cell lymphoma subtype that involved the bone marrow and liver. Analysis of serum samples showed a raised concentration of lactate dehydrogenase, suggesting a high–intermediate risk of non-Hodgkin lymphoma according to the international prognostic index, but no HIV-1. The patient received six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab, and achieved complete remission. 6 months after diagnosis and 2 months after complete remission was achieved, the patient was admitted to hospital because of loss of vision. In the early phase of the examination, a fluorescein angiogram of the right eye (figure A) showed two large hyperfluorescent infiltrates with granularity (arrows) with small regions of retinal pigment epithelial detachments (arrowheads). In the late phase of the study, the left eye (figure B) showed a diffuse retinal pigment epithelial detachment that remained densely hypofluorescent (arrows), suggesting presence of lymphoma. However, bone-marrow biopsy and a CT scan of the neck, chest, and abdomen showed no relapse of lymphoma. 6 days later, the patient became somnolent and agitated, and developed confusion and lethargy. A CT scan (not shown) and an MRI of the brain (figure C) showed multifocal intraparenchymal lesions. Histological and immunohistochemical analysis of a stereotactic biopsy sample of one of the frontal lesions showed presence of B-lymphocyte antigen CD20positive diffuse large B-cell lymphoma, and no presence of Epstein-Barr virus. The patient was given high-dose methotrexate followed by whole-brain radiotherapy. The patient died 1 month after CNS relapse because of disease progression.

Study of Pegylated Liposomal Doxorubicin in First Line Therapy of Aggressive Lymphomas.

Purpose: Conventional doxorubicin is currently used in many treatment protocols for lymphoma. Pegylated liposomal doxorubicin has a different pharmacokinetic profile with prolonged half life, reduced toxicity, especially cardiotoxicity and possible enhanced antitumor activity. This study was designed to evaluate tolerability and efficacy of pegylated liposomal doxorubicin in patients with aggressive lymphomas.Methods: Twenty-nine patients entered the study, 12 male, aged 36–86 (median 66 years), 22 with newly diagnosed CD20 positive diffuse large B-cell lymphoma (DLBCL), elderly with median age 77 years, 4 MALT in transformation, 2 mantle and one anaplastic. Patients' characteristics: IPI-1 10%, IPI-2 25%, IPI-3 10%, IPI-4 55%, stages III–IV 60%, bulky disease 40%, extranodal 55%. Combined immunochemotherapy with Rituximab 375 mg/m2, day1, added to standard CHOP was performed, 8 courses, with a follow up of nearly 3 years. Pegylated liposomal doxorubicin (Caelyx®) replaced doxorubicin at 30 mg/m2. Response was evaluated after 3 and 8 courses. Cardiac function was estimated at the beginning and after the end of therapy. LVEF, fractional shortening (FS) and myocardial performance index (MPI) according Tei et al, as most sensitive index for global LV function, were measured.Results: All responded except for three, one with active SEL and one with CNS lymphoma (refractory 10%). Overall response 91%, CR 76%, PR 15%, overall survival 82%, relapse rate 4.5% (1/22). No synergistic toxicity was observed, as there were no remarkable hematological or extrahematological toxic events. No clinical deterioration of cardiac function was observed. The patient with anaplastic lymphoma had severe preexisting cardiovascular disease and died from cardiac complications, in lymphoma remission. Two patients experienced a single episode of atrial fibrillation with successful pharmaceutical conversion. None developed alopecia, nausea, vomiting, palmar-plantar erythrodysesthesia, local injury in extravasation area. Treatment related mortality was documented in none. LVEF and FS were not changed, but MPI was slightly increased, detecting subclinical myocardial dysfunction.Conclusions: Pegylated liposomal doxorubicin is useful in the treatment of aggressive lymphomas, including elderly patients, well tolerated, producing durable complete remissions and offering advantages in combination with immunotherapy.

High CR Rate and Prolonged EFS in aaIPI 2 – 3 Diffuse Large B-Cell Lymphoma Following High-Dose Sequential Chemotherapy and In Vivo Rituximab-Purged Stem Cell Autografting (R-HDS Regimen): Results of a Prospective Phase II Multicenter Study Sponsored by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi).

Background. Recent reports have shown that Rituximab added to conventional chemotherapy may significantly improve the prognosis of CD20-positive Diffuse Large B-cell Lymphoma (DLB-CL). However, patients with unfavorable clinical presentation still have a poor outcome. Other studies have documented an increased anti-lymphoma activity upon addition of Rituximab to intensified treatments with autologous peripheral blood stem cell (PBSC) transplantation. Based on these premises, a prospective multicenter study has been performed on the use of a Rituximab-supplemented high-dose sequential (R-HDS) chemotherapy schedule with PBPC autografting in patients with unfavorable DLB-CL, defined as score 2 and 3 (intermediate-high or high) according to the age-adjusted International Prognostic Index (aaIPI).Methods. The R-HDS regimen included: (i) an initial debulkying with 3 APO courses; (ii) a high-dose (hd) phase consisting in the sequential administration, at 15–20 day intervals, of hd- cyclophosphamide (7gr/sqm, with two Rituximab doses at 375 mg/sqm), hd-Ara-C (2gr/sqm b.i.d. for 6 days with Rituximab), and hd etoposide + Cisplatin; (iii) a final myeloablative phase (hd-Mitoxantrone + L-Pam) with PBSC autografting and 2 more doses of Rituximab. Involved-field radiotherapy was scheduled on areas of previous bulky disease or residual lesions. Six Centers affiliated to the GITIL group (Gruppo Italiano Terapie Innovative nei Linfomi) participated in the multicenter study. Patient enrollment started in November 1999 and was closed in September 2004.Results. Overall, 112 previously untreated patients aged ≤ 60 years, with CD20-positive DLB-CL and aaIPI score 2 (74 pts) or 3 (38 pts), entered the study protocol and are evaluable. There were 5 early toxic deaths (3 sepsis in the hd-phase, 1 pneumonia and 1 leucoencephalopathy from JC-virus infection after autografting) and one late toxic death due to pneumonia which occurred at 10 mos. after R-HDS. The TRM was 5.3%. Ninety patients (80 %) achieved Complete Remission (CR). At a median follow-up of 24 mos, 90 patients (80%) are alive and 83 (74%) are in continuous CR (CCR), leading to a 5.3-yr event-free survival (EFS) projection of 71%. There was a trend towards a better outcome in aaIPI 2 vs. 3, although the difference was not statistically significant.Conclusions. The CR, OS and EFS rates observed after R-HDS compare favorably with the poor outcome anticipated in aaIPI 2–3 patients managed with conventional chemotherapy. The results of this phase II study prompted an ongoing phase III GITIL multicenter study to compare R-CHOP vs. R-HDS in younger patients with high-risk DLB-CL.

De novo CD5 Positive Diffuse Large B-cell Lymphomas with Bone Marrow Involvement in Korean

In CD5 positive (CD5+) mature B-cell lymphomas, newly recognized CD5+ diffuse large B-cell lymphoma (DLBCL) has been characterized by aggressive features. We studied twenty-five cases with CD5+ lymphomas involving bone marrow. Eleven cases were diagnosed as chronic lymphocytic leukemia, six cases were diagnosed as mantle cell lymphoma (MCL), and three cases with morphologic characteristics of MCL and without both the cyclin D1 expression and IGH/CCND1 rearrangement were unclassifiable. The remaining five cases, showing large to medium-sized lym-phoid cells with prominent nucleoli and a moderate amount of cytoplasm, were diagnosed as DLBCL. Five DLBCL cases were positive for CD5, CD20, surface immuno-globulin, but negative for CD23. Patients with CD5+ DLBCL showed a high age of onset (median, 68 yr) and two patients expired one month after the diagnosis. Since CD5+ DLBCL forms a distinct subgroup of DLBCL, a study of CD5 expression in DLBCL would be helpful to predict prognosis and to determine future therapeutic strategy. To the best of our knowledge, this is the first report on de novo CD5+ DLBCL in Koreans.

Extensive intraglomerular thrombi of monoclonal IgM-Κ in a patient with malignant lymphoma

We describe an 80-year-old man who developed malignant lymphoma (ML) complicated by extensive intraglomerular thrombi of immunoglobulin M (IgM)-Κ monoclonal immunoglobulin. The clinical picture was characterized by nephrotic syndrome and systemic lymphadenopathy. Laboratory examination showed mild anemia and a small amount of monoclonal IgM-Κ in the blood. The histopathologic findings and surface immunoglobulin analysis of the lymph node biopsy specimen were consistent with CD5-positive diffuse large B-cell (type, IgM-Κ) lymphoma. The subsequent renal biopsy showed a massive deposition of amorphous material in the glomerular capillary lumens, subendothelial areas, and mesangium. Nodular glomerulosclerosis was not found. An immunofluorescent study showed that the deposits consisted of IgM-Κ monoclonal immunoglobulin. Ultrastructurally, the deposits were composed of granular electron-dense material. Chemotherapy was effective for both the ML and nephrotic syndrome, and the patient's urine analysis results returned to normal. The histopathologic manifestations of this case are rare, and the pathogenesis of these glomerular lesions was obviously associated with ML.