scholarly journals CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin's disease

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2905-2917 ◽  
Author(s):  
DA Filippa ◽  
M Ladanyi ◽  
N Wollner ◽  
DJ Straus ◽  
JP O'Brien ◽  
...  

This study compares the histologic and immunophenotypic features of 71 cases of primary CD30+ diffuse large-cell lymphomas (DLCL) and 128 cases of Hodgkin's disease (HD) and discusses the clinical features of 52 patients with CD30+ DLCL. It includes analysis of sites of involvement, staging, response to treatment, sites and treatment of recurrences, and disease-free and overall survival. Diagnostic immunophenotypic differences were found between CD30+ DLCL and HD. All cases of CD30+ DLCL were positive for one or more common or lineage- specific lymphocyte antigens or for EMA. In contrast, 96.9% of HD cases were negative for CD45, CD45-RO, CD43, and CD20. The four exceptions are discussed. All cases of HD were negative for EMA. In patients with CD30+ DLCL, a T-cell phenotype was found in 60%, a null-cell type in 22%, and a B-cell type in 18% of the cases. The median age of patients with T- and null-cell phenotype was 22 years (range, 4 to 72). Fifty- two percent of them had high-stage (III and IV) disease and 61% had extranodal involvement at presentation, including 25% with skin lesions. Lymph nodes draining the skin lesions became involved in seven of 11 patients. No patient had initial bone marrow involvement. Most patients were treated with chemotherapy, and 83% had a complete remission. Fifty-four percent remain free of disease with a median follow-up of 47 months. Thirteen patients (29%) had one or more recurrences and five of them remain free of disease after salvage therapy, with a median follow-up period of 79 months. The clinical stage did not affect survival, probably as a result of different therapy. The t(2;5) translocation was found in five of 15 patients who had cytogenetic abnormalities. Of the other 10 cases, the translocation was detected by reverse transcriptase-polymerase chain reaction (RT- PCR) in four of five cases studied. All nine cases were of T- or null- cell phenotype. The cases of B-cell CD30+ DLCL had a characteristic immunophenotype. All were negative for EMA. These patients were older and had frequent bone marrow involvement but no skin infiltration by lymphoma. All three patients who were human immunodeficiency virus- positive (HIV+) had lymphomas of B-cell lineage. Detection of the t(2;5) translocation by molecular genetics is a useful and highly specific marker in the differential diagnosis between HD and CD30+ DLCL.

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 848-858 ◽  
Author(s):  
H Stein ◽  
DY Mason ◽  
J Gerdes ◽  
N O'Connor ◽  
J Wainscoat ◽  
...  

Abstract Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease- derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio- immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large- cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell- related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an “activation state.” In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.


1990 ◽  
Vol 8 (12) ◽  
pp. 1959-1965 ◽  
Author(s):  
A Tefferi ◽  
R A Zellers ◽  
P M Banks ◽  
T M Therneau ◽  
J P Colgan

Histologic and paraffin immunohistologic studies were carried out on 32 patients with lymphocyte-predominance Hodgkin's disease (LPHD) seen from 1970 through 1982. While nodular histology was accurately predictive of B-cell phenotype (Leu M1 -/L26+), diffuse histology corresponded to either B-cell or Hodgkin's (Leu M1 +/L26-) phenotype, not invariably predictable even when attention was paid to subtle paragranuloma cytology. Clinical characteristics were compared between histologic (diffuse v nodular) and immunophenotypic (Leu M1 +/L26-, Hodgkin's phenotype, v Leu M1 -/L26+, B-cell phenotype) subgroups. Ten patients have since died, and the median follow-up of the living patients was 14 years (range, 6 to 31). Of the several clinical parameters compared, only axillary nodal presentation was strongly associated with both B-cell phenotype and nodular histology, while male predominance related more to B-cell phenotype than nodular histology. No significant difference in overall survival or relapse rate was apparent among either the histologic or the immunophenotypic subgroups. However, very late but salvageable relapses were associated with nodular histology. The incidences of secondary malignancies and death from Hodgkin's disease (HD) were also comparable between the subgroups. Although difference in clinical presentation may exist, neither the histologic nor the immunophenotypic subcategories of LPHD could be demonstrated to correlate with differences in clinical outcome.


Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 848-858 ◽  
Author(s):  
H Stein ◽  
DY Mason ◽  
J Gerdes ◽  
N O'Connor ◽  
J Wainscoat ◽  
...  

Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease- derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio- immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large- cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell- related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an “activation state.” In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.


1981 ◽  
Vol 66 (4) ◽  
pp. 217-225 ◽  
Author(s):  
J.M. Andrieu ◽  
P. Cramer ◽  
B. Asselain ◽  
N. Tea ◽  
G. Tricot ◽  
...  

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 708-715 ◽  
Author(s):  
J Tamaru ◽  
M Hummel ◽  
M Zemlin ◽  
B Kalvelage ◽  
H Stein

Abstract The nature of Hodgkin and Reed-Sternberg (HRS) cells remains in question. Immunophenotypic studies favor a relation to the lymphoid lineage with the existence of B- and T-cell types. However, studies on the detection of antigen (Ag) receptor gene rearrangements provided inconsistent results. They concur in that rearranged Ig and T-cell receptor (TCR) genes are not demonstrable in most Hodgkin's disease (HD) cases. To clarify whether this is because of the insensitivity of the method of detection or a real absence of clonal Ig heavy chain (IgH) rearrangements, a polymerase chain reaction (PCR) method with high sensitivity was applied, allowing the detection of less than 50 cells with clonally rearranged IgH genes in a mixture of 100,000 germline or individually rearranged cells. In 67 cases of HD, most of those (67%) with B-Ag+ HRS cells express clonal VDJ rearrangements of the IgH gene. No cases with T-cell Ag+ HRS cells harbored detectable clonal VDJ rearrangements. Of 10 sequenced rearranged IgH genes, the VH segment of six contained considerable somatic mutations. These results suggest that the demonstrated VDJ rearrangements stem from the HRS cells themselves and that the HRS cells of cases with rearranged IgH genes are B-cell related and correspond in their differentiation stage either to naive pregerminal center B cells or (more commonly) to germinal center/postgerminal center-derived memory B cells.


1995 ◽  
Vol 13 (2) ◽  
pp. 403-409 ◽  
Author(s):  
R Munker ◽  
D Hasenclever ◽  
O Brosteanu ◽  
E Hiller ◽  
V Diehl

PURPOSE To describe the incidence of primary bone marrow involvement (BMI) in Hodgkin's disease (HD) and its correlation with clinical and laboratory features present at diagnosis, and to evaluate the prognostic relevance of BMI. PATIENTS AND METHODS Between 1983 and 1991, 2,307 patients with HD were treated according to two trial generations (HD1-3 and HD4-6) of the German Hodgkin's Lymphoma Study Group (GHSG). RESULTS One hundred thirty-five cases of primary BMI were observed. The incidence of BMI was 4.8% in the HD4-6 study generation, which included all stages. Among stage IV patients, 32% had BMI. Among those with BMI, other organs were also involved in 33%. Among all patients, the presence of BMI was significantly associated with B symptoms, lymph nodes on both sides of the diaphragm, mixed cellularity histologic subtype, leukocytopenia, anemia, thrombocytopenia, lactate dehydrogenase (LDH) level more than 400 U/L, and erythrocyte sedimentation rate (ESR) more than 40 mm/h. BMI was negatively correlated with a large mediastinal tumor (3.7% v 20.0% in non-BMI cases). Eighty-seven of 108 (81%) assessable patients with BMI achieved a complete remission (CR). This compares favorably with the overall CR rate in all stage IIIB/IV patients. Among stage IV patients, BMI has no prognostic relevance with regard to freedom from treatment failure and overall survival. Twenty-one patients with BMI relapsed after having achieved a CR. Only five of these (24%) again had a positive bone marrow biopsy. CONCLUSION The prognosis of patients with BMI is not worse than the prognosis of other advanced-stage HD patients. BMI alone does not define a special high-risk group in which a different treatment approach is indicated.


1983 ◽  
Vol 69 (1) ◽  
pp. 47-51 ◽  
Author(s):  
Giuseppe Cimino ◽  
Anna Paola Anselmo ◽  
Anna Maria De Luca ◽  
Paola Fidani ◽  
Francesca Mauro ◽  
...  

Bilateral trephine bone marrow biopsies of 370 patients with Hodgkin's disease first seen at the Institute of Hematology, University of Rome, between 1970 and 1981, revealed tumor involvement of the bone marrow in 18 cases. The histologic type was mixed cellularity in 7 cases, lymphocytic depletion in 4 cases, nodular sclerosis in 4 cases, and lymphocytic prevalence in 1 case. Anemia with less than 10 g/dl of hemoglobin was observed in 5 patients; white blood cells were less than 4.0 × 109/liter in 2 patients; platelets were less than 12.0 × 109/liter in 1 case; a pancytopenic condition was observed in only 1 case. B symptoms were present in 14 of the 18 patients. All patients who underwent laparosplenectomy presented spleen involvement, 4 also had liver involvement. All patients were treated with chemotherapy; MOPP regimen was employed in 11 cases, ABVD in 5 patients, and PROVECIP in 1 case. Of the 13 patients evaluable for therapeutic response, 11 achieved complete remission, with a median actuarial relapse-free survival of 15 months. The actuarial survival curve showed that 50% of all patients are projected alive at 47 months with a follow-up ranging from 1 to 109 months.


2003 ◽  
Vol 1 (5) ◽  
pp. S301
Author(s):  
S. Kanaev ◽  
S.N. Novikov ◽  
L. Jukova ◽  
M. Girschovich

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2083-2083
Author(s):  
Brian Bolwell ◽  
Brad Pohlman ◽  
Matt Kalaycio ◽  
Steve Andresen ◽  
Elizabeth Kuczkowski ◽  
...  

Abstract Long-term results of conventional therapy of Hodgkin’s disease (HD) has demonstrated the importance of long-term and ongoing follow-up given the potential for later complications after curative therapy. While many transplant series report follow-up of several years after ABMT, few report a 15-year experience from a single institution. This report examines the outcomes of 220 patients receiving high-dose chemotherapy and autologous stem cell transplant (ABMT) at The Cleveland Clinic Foundation from January 1990 through June 2005. Median age was 33 years (range, 14–70 years); median time from diagnosis to transplant was 19 months; 47% received prior radiation therapy; 82% had nodular sclerosis histologic subtype; number of courses of prior chemotherapy were: 1 (16%), 2 (66%), 3 (14%), 4 or more (4%). All patients received salvage therapy prior to transplant: 29% were in a complete remission (CR), 55% in a partial remission (PR), and 16% refractory. All patients received a chemotherapy-only preparative regimen, most commonly Bu/Cy/VP (73%), followed by CBV (17%). 78% received peripheral stem cells alone; 22% received either autologous bone marrow or a combination of bone marrow plus peripheral stem cells. At the present time 60% of patients are alive. Of the 88 patients who died, the most common cause of death is relapse (69% of deaths). Secondary malignancy occurred in 11 patients (5%); 9 of these cases were secondary AML/MDS and 5 of these patients with secondary malignancies have died. 44% of the entire cohort has relapsed, at a median of 9 months post-transplant (range, 1.4–76 months). 10-year overall survival is 47%. A multivariable analysis showed that the two significant variables that correlated with post-BMT relapse were the number of prior chemotherapies (p = 0.011), and patients treated in remission vs. those not in remission (p = 0.002). Of patients receiving 2 or more prior courses of chemotherapy, 60% have relapsed 8 years post-transplant, compared to 40% of those receiving one course of prior chemotherapy. The risk of relapse by the number of prior chemotherapy courses is shown graphically below: Figure Figure In conclusion, this very large series of ABMT for recurrent HD with long-term follow-up demonstrates the importance of timely autografting in relapsed HD patients. The optimal time to proceed with ABMT is after failing one, and only one, course of chemotherapy. Delaying transplant for unrealistic long-term salvage with other courses of traditional chemotherapy will negatively affect the outcome of subsequent ABMT.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2866-2866
Author(s):  
Katarina Luptakova ◽  
Michelle Kim ◽  
Pamela Ely ◽  
Barbara Grant ◽  
John Anthony Parker ◽  
...  

Abstract Abstract 2866 Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy and is generally responsive to anthracycline-containing chemotherapy. However, 60% of patients (pts) will relapse after their first line treatment. At the time of relapse the only curative approach includes the use of a stem cell transplant (SCT). The incidence of DLBCL increases with age which creates a subset of pts who are not candidates for first line anthracycline-based chemotherapy, and a large subset of pts who are not candidates for SCT due to advanced age and/or co-morbidities. Thus, there is a significant unmet need for therapies with a low toxicity profile in elderly or medically unfit pts with DLBCL. 90Y-ibritumomab tiuxetan (90Y-IT) is an anti-CD20 murine antibody linked with a beta-emitting isotope approved for use in indolent lymphoma. Maintenance rituximab (R) has been reported to increase response rates and prolong remission duration in some lymphomas. We performed a phase II multicenter clinical trial to examine the efficacy of 90Y-IT induction followed by maintenance R in pts with DLBCL. Patients and Methods: Eligible pts were either intolerant of anthracycline-based chemotherapy or had relapsed or refractory CD20+ DLBCL with measurable disease. Pts had to be ineligible for SCT for reasons other than failure to harvest stem cells. Bone marrow involvement by lymphoma of less than 25% based on bilateral bone marrow aspirate and biopsy was required. R 250 mg/m2 was administered IV immediately followed by 111In-ibritumomab tiuxetan. Nuclear scans were performed at 24 and 48 hours to insure there was no altered biodistribution. On day 8 a second infusion of R 250 mg/m2 followed by 0.4 mCi/kg (for pts with a baseline platelet count >150,000/mm3) or 0.3 mCi/kg 90Y-IT (for pts with a baseline platelet count 100,000-149,000/mm3) was given. Pts with multiple extranodal sites or prior bone marrow involvement received CNS prophylaxis with intrathecal methotrexate or cytarabine. Maintenance R 375 mg/m2 was given on weeks 3–6, then weekly × 4 every 6 months × 4 cycles or until progression. Results: Between 10/2003 and 9/2009, 25 pts have been treated. During the course of the study, the ownership of the therapeutic agent changed three times and therefore enrollment was interrupted on two occasions. The median age of pts was 79 (range 45–91), 36% pts had a sIPI score 3 or more. The median number of prior regimens is 2 [0-5]. The 90Y-IT treatment regimen produced an overall response rate of 36% [9 pts] with 28% CR [7 pts]. To date, the mean OS is 18 months (median 8.1 months) with a median follow-up of 11.2 months. Among responding pts, the median OS has not been reached with a median follow-up of over 26.2 [0.1-71.4] months. Thirteen pts died within the first year, 6 patients (24%) continue to be in remission greater than 18 months, and 4 patients (16%) remain in long-term remission [39.9-71.4 months]. The most frequently observed toxicity was hematologic. Eleven percent of pts had grade 4 neutropenia with only one patient experiencing febrile neutropenia, and 16% of pts experienced grade 4 thrombocytopenia. There were no unexpected non-hematologic toxicities except for 1 patient that experienced extravasation. One late-occurring case of MDS/AML was reported that is possibly related to the study regimen, and one case of adenocarcinoma of the GI tract that is likely unrelated. Of note, none of the pts that progressed on the chemotherapy preceding this study achieved a response to the study regimen. Conclusions: The 90Y-IT treatment regimen has an acceptable toxicity profile in elderly or heavily pretreated pts with DLBCL. The two week outpatient 90Y-IT infusion produces response rates and durations similar to that of more prolonged cytotoxic chemotherapy regimens. Progression on previous chemotherapy predicts for poor response to 90Y-IT. Treatment with 90Y-IT can provide durable remission to a select subset of pts who are not candidates for SCT, or intensive anthracycline based chemotherapy. Disclosures: Off Label Use: We are describing a phase II study of the use of 90Y-Ibritumomab Tiuxetan for treatment of diffuse large B-cell lymphoma. Current FDA approved use of 90Y-Ibritumomab Tiuxetan includes relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL) or previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy. Joyce:Spectrum Pharmaceuticals, Inc.: Research Funding; Cell Therapeutics Inc: Research Funding; Biogen Idec: Research Funding.


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