Nodular mixed lymphoma: results of a randomized trial failing to confirm prolonged disease-free survival with COPP chemotherapy

Fifty-two patients with stage III or IV nodular mixed lymphocytic- histiocytic lymphoma (NM) were entered on a prospective randomized trial comparing cyclophosphamide-prednisone (CP) to either COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or BCVP (BCNU, cyclophosphamide, vincristine, prednisone). The COPP regimen utilized in this Eastern Cooperative Oncology Group (ECOG) trial was similar to the four-drug regimen C-MOPP reported by the National Cancer Institute to achieve prolonged relapse-free survival in this histology. No significant differences in complete response rates, response duration, or overall survival were noted among the three regimens. A pattern of continuous late relapse was observed for all three chemotherapy programs. Although 11 of the 18 (61%) COPP patients achieved a complete response, only 3/11 (27%) remain disease-free with a median follow-up of over 3 yr. However, two of these three long-term complete responders have died with no clinical evidence of recurrent disease. The COPP patients received 84% of the calculated ideal doses of cyclophosphamide and 78% of the ideal dosage of procarbazine. Grade 3-4 hematologic toxicity was noted in 22% of the COPP group, 36% with BCVP, and 0% for the CP patients. We were unable to confirm the ability of COPP to achieve durable complete remissions in NM lymphoma. The cyclophosphamide-prednisone combination was equally effective when compared with COPP and BCVP, but produced minimal toxicity.     

CALLA-positive myeloma: an aggressive subtype with poor survival

Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group.     

Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) are distinct tumors and are treated differently. They are linked by a morphologic and probably a biologic continuum, which renders the differential diagnosis difficult. To develop criteria to distinguish the entities along the morphologic continuum, we correlated the lymph node architecture and immunophenotype of both tumor cells and reactive components of 235 neoplasms in the spectrum of NLPHL and T/HRBCL with clinical data. Two hundred and eighteen cases fitted the World Health Organization (WHO) criteria of NLPHL (139) or T/HRBCL (79). While tumor cells in both entities were immunophenotypically similar, background composition differed: in NLPHL small B cells and CD3⁺CD4⁺CD57⁺ T cells were common, whereas in T/HRBCL, CD8⁺ cytotoxic T cells and histiocytes dominated. Follicular dendritic cells (FDCs) formed expanded meshworks in NLPHL, whereas they were absent in T/HRBCL. Seventeen cases represented a gray zone: within FDC meshworks, neoplastic B cells resided in a background depleted of small B cells but rich in T cells and histiocytes. Tumor cells either were loosely scattered or formed clusters, thus resembling areas of either T/HRBCL or inflammatory diffuse large BCL (DLBCL) within the nodules. Patients with these NLPHLs with T-cell/histiocyte-rich nodules presented at a high stage and with B symptoms, as in T/HRBCL, but had an excellent survival, as in NLPHL. This morphologic pattern suggests a biologic continuum between NLPHL and T/HRBCL. (Blood. 2003;102:3753-3758)      

Long-term disease-free survival of patients with advanced follicular lymphoma after allogeneic bone marrow transplantation

Myeloablative allogeneic bone marrow transplantation (BMT) may be curative in patients with follicular non-Hodgkin's lymphoma, however, the impact of this therapy on long-term survival, disease progression and functional status is less clear. Twenty-nine patients (median age 42 years, range: 20-53) with advanced stage follicular lymphoma proceeded to allogeneic BMT a median of 25 (range: 8-154) months postdiagnosis, between 1985 and 2001, and have been followed for a minimum of 2 years. Eleven of 29 (38%) had refractory disease (n = 5 induction failure, n = 6 resistant relapse). Most (27 of 29, 93%) received total body irradiation-based conditioning; stem cell source was marrow from a related donor (n = 20) or unrelated donor (n = 9). Seventeen of 29 patients (59%) were alive a median of 5 years (range: 2-11) post-BMT with a median Karnofsky Performance Score of 100%. Death occurred because of transplant complications in seven patients (cumulative incidence of non-relapse mortality 24%), and progressive lymphoma in five patients (cumulative incidence of refractory/recurrent lymphoma 23%). The 5-year probability of overall and event-free survival was 58% and 53% respectively. Allogeneic BMT has resulted in long-term disease-free survival for approximately 50% of this cohort of patients with advanced follicular lymphoma and most of them now enjoy robust health.     

Follicular large cell lymphoma: an aggressive lymphoma that often presents with favorable prognostic features

It is debated whether follicular large cell lymphoma (FLCL) has a clinical behavior that is distinct from indolent follicular lymphomas, and whether there is a subset of patients who can be potentially cured. We report here our experience with 100 FLCL patients treated at our institution since 1984 with three successive programs. We evaluated the predictive value of pretreatment clinical features, including two risk models, the Tumor Score System and the International Prognostic Index (IPI). With a median follow-up of 67 months, the 5-year survival is 72% and the failure-free survival (FFS) is 67%, with a possible plateau in the FFS curve, particularly for patients with stage I-III disease. Features associated with shorter survival included age >/=60, elevated lactic dehydrogenase (LDH) or beta-2-microglobulin (beta2M), advanced stage, and bone marrow involvement. Stage III patients had significantly better survival than stage IV patients (P <.05). By the IPI and Tumor Score System, 80% of the patients were in the lower risk groups; both systems stratified patients into prognostic groups. Patients with FLCL have clinical features and response to treatment similar to that reported for diffuse large cell lymphoma. Prognostic risk systems for aggressive lymphomas are useful for FLCL. A meaningful fraction of patients may possibly be cured when treated as aggressive lymphomas.     

Intracranial histiocytic lymphoma with rheumatoid arthritis.

A patient with classical rheumatoid arthritis presented with a primary intracranial histiocytic lymphoma. He had not received cytotoxic drugs and had no evidence for Sj?gren's syndrome or immunodeficiency. Previous radiation therapy to the shoulders is regarded as a possible, though unlikely, risk factor.     

Prolonged disease-free survival in relapsed/refractory low-grade lymphoma treated with fludarabine: a report of four cases

We report four patients with relapsed or refractory follicular (three) and lymphoplasmacytic (one) lymphoma who achieved complete remission (CR) with fludarabine (FDR) lasting from 3.2 to 6 years. One had stage III and three stage IV and were resistant to chlorambucil and/or anthracycline. FDR was well tolerated, the only complication being herpes zoster infection in three patients, which was controlled with aciclovir. One patient developed a gastric MALT lymphoma from a different clone than the follicular lymphoma. In conclusion, some patients with refractory low-grade lymphoma achieve long-term CR with FDR; therefore this agent may be considered as alternative to stem-cell transplantation.     

Survival of patients with localized diffuse histiocytic lymphoma

Twenty-eight patients with previously untreated diffuse histiocytic lymphoma (DHL) were identified to be in pathologic stage (PS) I (11), IE (3), II (8), or IIE (6) by exploratory laparotomy and splenectomy. Six patients were treated with total nodal radiotherapy; 14 with an extended mantle; 5 with an inverted Y or whole abdomen; and 3 with an involved field. Twenty-six patients achieved a complete remission (93%) and 2 patients had persistent local disease. The median survival and disease-free survival and for the complete response group are 56 and 51.5 mo, respectively. Ten of the 11 stage I or IE patients had supradiaphragmatic lymph node disease. Patients with stage I or IE disease (n = 14) demonstrated a median survival of 72.5 mo and a median disease-free survival of 69.5 mo; there was 1 disease-related death. Patients with stage II or IIE disease (n = 14) demonstrated a median survival of 33 mo and median disease-free survival of 29.5 mo; there were 10 relapses or deaths. Patients in stages I, IE, II, or IIE with infradiaphragmatic disease (n = 7) had a median survival of 36 mo, while patients with supradiaphragmatic presentation (n = 21) demonstrated median survival of 68 mo (p = 0.37). The data indicate that patients with diffuse histiocytic lymphoma with stage I supradiaphragmatic lymph node disease are curable using radiotherapy alone, achieving a 93% 11-yr actuarial disease-free survival. Patients with stage II or IIE diseases are not readily curable with radiation therapy alone, achieving a 33% 11-yr actuarial disease-free survival; radiotherapy with adjuvant chemotherapy or chemotherapy alone should be considered for this group.     

True histiocytic lymphoma following therapy for lymphoblastic neoplasms

True histiocytic lymphomas (THLs) are rare tumors in which the malignant cells show morphologic and immunophenotypic evidence of histiocytic differentiation. We describe THLs that arose after therapy for one case of T-lineage lymphoblastic lymphoma (LyL) and two cases of acute lymphoblastic leukemia (ALL) (both CD10+, one pre-B phenotype). The lymphoblastic neoplasms were not unusual in any way, and responded well to standard therapy. The THLs arose 10 to 20 months after complete remission was achieved for the lymphoblastic neoplasms, at which time there was still no clinical or pathologic evidence of the lymphoblastic neoplasms. All three THLs exhibited clinical and morphologic features of malignancy. Neoplastic cells in the THLs had abundant eosinophilic vacuolated cytoplasm and pleomorphic nuclei, and expressed histiocytic antigens in the absence of lymphocyte-specific lineage markers. Because THLs are rare neoplasms, their occurrence after otherwise successful therapy for lymphoblastic neoplasms in these three cases may constitute a distinct clinicopathologic entity.     

Relapsing large cell immunoblastic lymphoma complicating well-differentiated lymphocytic lymphoma: a report of two cases showing prolonged survival with therapy

Two patients presented with co-existing large cell immunoblastic and well-differentiated lymphocytic lymphomas. Prolonged remissions from the large cell lymphomas were achieved following intensive combination chemotherapy but both patients suffered relapses after many years. Previous reports have grouped such patients with those developing classical Richter's syndrome implying a uniformly poor prognosis. This report suggests that this is not the case. It was not possible with immunohistochemical stains to prove or disprove that these tumours had the same stem cell origins.     

Aggressive chemotherapy for diffuse histiocytic lymphoma in the elderly: increased complications with advancing age

Twenty patients greater than or equal to 70 years of age were included in a study of the treatment of diffuse histiocytic lymphoma utilizing cyclophosphamide, adriamycin, vincristine, and prednisone. These patients ranged in age from 70 to 94 years (median 75 years). There were also 55 younger patients (age range 33 to 69 years) in the treatment trial. There were no dose adjustments for age. The complete remission rate in the elderly patients (45 per cent) was not different from that in the younger patients (53 per cent). The overall survival in the elderly patients (median 13 months) was somewhat shorter than that in the younger patients (medians 22 months for patients 56-69 years of age and 41 months for patients 33-55 years of age), but not significantly different. Death during the first two treatment cycles from causes other than lymphoma occurred in 25 per cent of the patients greater than or equal to 70 years of age versus 2 per cent of younger patients (P less than 0.01). In addition, three other patients aged 79, 65, and 59 years died in the fourth or fifth cycles of treatment from causes other than lymphoma. Thus, 30 per cent of patients greater than or equal to 70 years of age died during therapy from causes other than lymphoma, versus 5 per cent of younger patients (P less than 0.01). Whether this altered ability to tolerate therapy in the older patients reflected decreased marrow function, altered drug metabolism, other effects of aging, or a combination of these factors is not clear. It might be appropriate to alter drug doses when treating elderly patients, and particular attention to supportive measures seems appropriate.     

Diffuse histiocytic lymphoma in a patient treated with cyclophosphamide for Wegener's granulomatosis

Diffuse histiocytic lymphoma developed in a 48-year-old man with Wegener's granulomatosis after nine years of therapy with cyclophosphamide. He died despite aggressive surgical and medical therapy for the lymphoma. This may be the first report of diffuse histiocytic lymphoma following treatment of Wegener's granulomatosis with cyclophosphamide. Recommendations for the approach towards extended therapy of smoldering Wegener's granulomatosis are discussed.     

Strategies for aggressive T-cell lymphoma: divide and conquer

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