Correlation of monoclonal antibody phenotyping and cellular DNA content in non-Hodgkin's lymphoma. The Southeastern Cancer Study Group experience

Flow cytometric measurements of DNA ploidy and synthetic (S) fractions are quantitative parameters that can aid in the diagnosis and classification of non-Hodgkin's lymphomas (NHL). Although the S-fraction correlates with histologic classification, the relationship between specific immunologic phenotypes and DNA ploidy is less well known. We investigated this relationship in 106 cases of NHL. Samples from 17 SEG institutions were sent for flow cytometry and for frozen section immunoperoxidase phenotyping. DNA histograms were analyzed for ploidy changes and cases classified by degree of abnormality. Ninety-eight cases were B-cell and eight were T-cell. B-cell tumors were subdivided by expression of antigens CD24, CD10, CD5, HB31, CD22, CD20, and transferrin receptor. Among B-cell tumors there was no correlation between degree of aneuploidy and phenotype, but B-cell tumors displayed a higher degree of aneuploidy than T-cell tumors (P less than 0.02). There was no difference between the S-fractions of B-cell and T-cell lymphomas. However, the transferrin receptor was more often expressed when the S-fraction was higher than 5%. Cases with S-fractions higher than 5% were more likely to lack any of the Pan-B antigens CD19, CD22 or CD20, and also were more frequently CD24 negative. We conclude that T-cell and B-cell NHL differ in degree of aneuploidy, and that monoclonal antibody phenotyping and DNA ploidy analysis independently define subgroups of B-cell NHL. Within B-cell lymphomas phenotype also correlates with grade of NHL as defined by the S-fraction.     

T-cell-rich lymphoproliferative disorders. Morphologic and immunologic differential diagnoses

To differentiate peripheral T-cell lymphomas (PTCL), the authors evaluated the results of T11 monoclonal antibody studies on consecutive cell suspensions prepared from 509 lymph nodes from various lymphoproliferative disorders (LPD). They used T11 (CD2) positivity to identify those LPD in which the content of T cells was high. There were 266 (52%) cell suspensions which contained more than 50% T11-positive cells. More than 75% of the following non-Hodgkin's lymphomas had over 50% T11-positive cells: diffuse mixed cell (DM), diffuse atypical poorly differentiated lymphocytic and lymphoblastic lymphomas; mycosis fungoides; and true histiocytic lymphoma. Eleven cell suspensions had more than 90% T11-positive cells; four were involved by B-cell lymphomas. The cell suspensions prepared from nine of 14 diffuse large cell lymphomas of the T-cell type had more than 50% T11-positive cells. Of these, three of five cases of the polymorphous subtype had fewer than 50% T11 cells, but six of seven lymph nodes of the clear-cell type had more than 50% T11-positive cells. Each of seven DM samples of the T-cell type contained over 50% T11 cells; none had a polymorphous appearance. In the 112 cases of reactive LPD studied, more than 75% of cases of necrotizing lymphadenitis, dermatopathic lymphadenitis, angioimmunoblastic lymphadenopathy, and those with lymph nodes with no specific reactive pattern had more than 50% T11-positive cells. The authors' findings indicate that T11 positivity is a reliable T-cell marker in reactive and neoplastic LPD except for those cases of PTCL with a polymorphous appearance; these tend to lose T11-expression. A multi-parameter diagnostic approach is required in the following LPD: (1) PTCL which are T11-negative; (2) PTCL of small lymphocytic type having an unremarkable T-cell phenotype; (3) SIg-negative B-cell lymphomas which are rich in nonneoplastic T cells; (4) non-Hodgkin's lymphomas with minimal disease which are rich in reactive T cells; and (5) polymorphous large cell proliferations.     

Association of DNA content and proliferative activity with clinical outcome in patients with diffuse mixed cell and large cell non-Hodgkin's lymphoma

Formalin-fixed and paraffin-embedded lymph node biopsy specimens from 52 untreated patients with newly diagnosed diffuse large cell (n = 48) or mixed cell (n = 4) non-Hodgkin's lymphoma (NHL) were analyzed for DNA content and proliferative activity (PA) by flow cytometry. The results obtained by flow cytometry were compared with the results of cytogenetic studies performed on 28 of the specimens. The median age of the patients was 65 years (range, 15-84 years) and the male to female ratio was 3 to 2. All patients were uniformly staged and uniformly treated with cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone. The flow cytometric results were compared statistically by univariate analysis with the rate and duration of complete remission and survival. Tumors with low PA (greater than or equal to 80% of cells in G0/G1 phase) were found in 65% of the patients; 74% of those with low PA versus only 44% of those with high PA achieved an initial complete remission (P less than 0.02). DNA aneuploidy was detected in tumors of 56% of the patients and was associated with a significantly longer duration of complete remission (P less than 0.01). Both low PA and aneuploidy independently predicted longer survival. The predicted 2-year actuarial survival for patients with tumors with low PA was 68% versus 10% for those with high PA (P less than 0.01). Similarly, the 2-year survival of patients with aneuploid tumors was 60% versus 36% for those with diploid tumors (P less than 0.01). The combination of PA and DNA content categorized the patients into four groups with decreasing 2-year survivals: low PA/aneuploid (n = 20), 77%; low PA/diploid (n = 14), 57%; high PA/aneuploid (n = 9), 32%; high PA/diploid (n = 9), 0%. The flow cytometric results correlated well with those of the cytogenetic studies. We conclude that low PA and DNA aneuploidy, both separately and in combination, predict a favorable clinical outcome for patients with diffuse mixed cell and large cell NHL.     

Clinical and biological analysis of peripheral T-cell lymphomas: a single institution study.

Peripheral T-cell lymphoma (PTCL) accounts for 15-20% of non-Hodgkin's lymphoma in the Western World. Clinical, histopathologic, phenotypic and genotypic data were received from 33 cases of PTCL referred to our institution. The median age order was 50 years, 78% were males, and 18% had a history of a preceding disorder of the lymphoid system. 60% had stage 4 at diagnosis and B symptoms were also present in 60%. The most frequent sites of extranodal involvement were bone marrow (54%), liver (45%) and skin (33%). Twenty-eight of 33 cases were histologically classified according to the Working Formulation (most in the diffuse mixed and large-cell subgroups) and the Kiel updated system. Phenotypic and genotypic studies of malignant cells showed a considerable heterogeneity with respect to the expression of either T-cell receptor (TCR) alpha beta and gamma delta and pan-T differentiation molecules. Of the studied cases 63% expressed TCR-alpha beta. All five patients with PTCL of the TCR-gamma delta subtype had a peculiar extra-nodal presentation. The vast majority of cases expressed an abnormal T-cell phenotype with respect to the expression of pan-T antigens, including the lack of expression of the TCR-associated CD3 molecule in 2 cases. Rearrangements of the TCR beta and/or delta-chain genes showed clonality in 21 of the 23 studied cases. Twenty-five patients were treated with a multiagent chemotherapy regimen with curative intent and the remainder received a less intensive palliative regimen. Only 9 patients achieved CR (8 of whom had received an anthracycline-containing regimen) and the 4-year survival rate was 25%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades--should peripheral T-cell lymphoma be considered separately?

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.     

Peripheral T-cell lymphoma

Peripheral T-cell lymphoma is the most common type of T-cell lymphoma seen in adults in the United States. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 years), 59% were male, and 36 patients (27%) had a history of a preceding disorder of the immune system. The tumors were grouped histologically into large cell (43%), mixed large and small cell (40%), and small cell (17%). The stage at diagnosis was I (7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkin's lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (nine patients), or no treatment (nine patients). Fifty percent of the intensively treated patients achieved complete remission and the actuarial 4-year survival was 45%. However, the 4-year, disease-free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterparts, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook.     

Peripheral T-cell lymphomas, unspecified (or not otherwise specified): a review

Peripheral T-cell lymphomas (PTCL) comprises a heterogeneous group of haematological tumours, which originate from mature T-cells, and constitute less than 15% of all non-Hodgkin's lymphomas (NHLs) in adults. The current WHO classification recognizes nine distinct clinicopathologic peripheral T-cell NHLs, being the 'unspecified variant' (PTCL-U) the most common subtype. These neoplasms often present in advanced stage at diagnosis, and most commonly have an aggressive clinical course requiring prompt treatment. The rarity of these tumours requires additional studies to better understand their biology and search for new therapies which may hopefully improve the dismal outcome of most patients. This review aims to describe the pathobiological aspects as well the clinical characteristics and current therapeutic strategies of the PTCLs, with special attention to the group of PTCL-U.     

外周T细胞淋巴瘤研究进展

 外周T细胞淋巴瘤（PTCL）为一组异质性淋巴细胞恶性增殖性疾病,起源于胸腺后成熟T淋巴细胞或自然杀伤细胞。与B细胞淋巴瘤相比,PTCL侵袭性更强,预后更差。综述PTCL的临床诊断与治疗进展。     

High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience.

BACKGROUND: T-cell immunophenotype constitutes an unfavorable prognostic factor in aggressive non-Hodgkin's lymphomas. High-dose chemotherapy with autologous stem-cell rescue (HDC/ASCT) is the best salvage therapy for patients with aggressive B-cell lymphomas. However, results with this therapy in peripheral T-cell lymphoma (PTCL) are not well defined. PATIENTS AND METHODS: From January 1990 to December 1999, 115 patients with PTCL underwent HDC/ASCT inside the Grupo Espa?ol de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) registry. At diagnosis the median age was 41 years and 60% of patients presented with two or three risk factors from the adjusted International Prognostic Index (a-IPI). Thirty-two per cent of patients were transplanted in first complete response (CR), 62% in chemosensitive disease and 5% in refractory disease. RESULTS: Eighty-six per cent of the patients attained a CR and 5% a partial response (PR). With a median follow-up of 37 months (range 1-133), overall survival (OS), time-to-treatment failure (TTF) and disease-free survival (DFS) at 5 years was 56%, 51% and 60%, respectively; for the 37 patients transplanted in first CR, OS and DFS at 5 years were 80% and 79%, respectively. Lactase dehydrogenase (LDH), a-IPI and disease status pre-transplant were associated with outcome. CONCLUSIONS: More than half of patients with chemosensitive disease who were transplanted are expected to be alive at 5 years. We confirm the utility of the pre-transplant IPI system in predicting outcome. Salvage treatment results with HDC/ASCT in PTCL are similar to those found in corresponding aggressive B-cell lymphomas.     

Hematopoietic stem cell transplantation in peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCL) are a rare entity with a dismal outcome. After conventional chemotherapy they showed a worse prognosis compared with B-cell non-Hodgkin's lymphoma (NHL), except for anaplastic lymphoma-kinase (ALK)-positive anaplastic large cell lymphomas (ALCL). High-dose chemotherapy followed by autologous stem cell transplantation (SCT) has been evaluated in relapsed patients as well as in the upfront setting. Available data showed an advantage for patients who received transplant as first line treatment whereas results of autografting at relapse have been satisfactory only for ALK-positive ALCLs compared to other PTCL subtypes. Based upon preliminary results, allogeneic SCT can be also considered as an alternative strategy in these lymphomas. Whether or not the postulated graft-versus-lymphoma effect may overcome the poor prognosis of T-cell NHL patients has to be established.     

Flow cytometric analysis of DNA ploidy in large cleaved cell lymphomas

The results of nuclear DNA content analysis of a series of 28 patients with large cleaved follicular centre cell non-Hodgkin's lymphomas (NHL) are reported. DNA aneuploidy was found in 11 (39 per cent) cases. The DNA indices of the DNA-aneuploid peaks ranged from 1.14 to 2.28. Seven (25 per cent) cases were tetraploid. DNA ploidy was not associated with prognosis. The percentage of S phase cells (SPF) ranged from 2.0 to 30.5 per cent (median 5.1 per cent). Lymphoma patients with SPF higher than 9.7 per cent had a worse survival rate than patients with lymphoma with less than 9.7 per cent S phase cells but the difference did not reach statistical significance. The results of the DNA ploidy and SPF were comparable to those of intermediate and high grade malignancy NHLs.     

造血干细胞移植治疗外周T细胞淋巴瘤的进展

The general chemotherapy for Peripheral T-cell lymphoma(PTCL) featuring an active invasion has less curative effect and worse prognosis in comparison with that for B-cell non-Hodgkin's lymphoma(NHL).Studies in recent years suggest that hematopoietic stem cell transplantation(HSCT) has better curative effect on the PTCL;however,it is significant to do more studies on some aspects such as the methodology,punctuality,preconditioning,and pretreatment intensity of the transplantation,which are crucial to the cur...     

Peripheral T-Cell Lymphomas Respond Well to Vincristine, Adriamycin, Cyclophosphamide, Prednisone and Etoposide (VACPE) and Have a Similar Outcome as High-Grade B-Cell Lymphomas

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of T-cell malignancies including subentities with favourable (large cell anaplastic) or unfavourable (pleomorphic) prognosis. The clinical outcome of PTCL has been controversially discussed, but a worse prognosis than high-grade B-cell Non-Hodgkin's lymphomas (NHL) has been postulated by most authors. In this report we summarize the results of a prospective comparative study investigating the therapy outcome of 27 patients (pts) with PTCL and 55 pts. with high grade B-cell NHL and give an overview of therapy studies in PTCL. The histological sub-types were 14 pleomorphic, 8 large-cell anaplastic (Ki-1+), 2 angioimmunoblastic (AILD) and 3 other PTCL. In three patients the PTCL was associated with non-tropical sprue (11%). Nineteen patients presented with an advanced stage of disease (stage III and IV, 70%), 17 (63%) pts. had B-symptoms. The patients were treated with vincristine 2 mg dl, adriamycin 25 mg/m² dl-3, cyclophosphamide 800 mg/m² dl, prednisone 60 mglm² dl-7 and etoposide 120 mg/m² dl-3 (VACPE). In 77% of pts. with PTCL and 84% of patients with high-grade B-cell NHL a complete remission (CR) was achieved. 75% of the complete responders with PTCL and 70% with B-NHL are still in ongoing CR. The subgroup of large-cell anaplastic attained a CR in 88%. The median observation time is 44 months (1+-77+). The probability of 1-, 3- and 5-year overall and disease-free survival for the T-cell group were 76%, 54%, 48% and 76%, 62%, 62%, respectively according to Kaplan-Meier. There was no significant difference regarding the remission rate, the overall-, event-free or disease-free survival compared to high-grade B-cell lymphomas.

In conclusion, the VACPE regimen is an effective and feasible regimen in the management of PTCL achieving complete remissions in a large proportion of patients.     

Prognostic significance of flow cytometric analysis of DNA content in colorectal cancer: A prospective study

We prospectively analyzed the tumor DNA content by flow cytometry in 100 patients who underwent a curative resection for colorectal cancer between August 1989 and May 1992 in order to evaluate the prognostic significance of DNA ploidy and the DNA index (DI). Patients with aneuploid tumors were found to have a significantly shorter disease-free survival than those with diploid tumors (P = 0.014). In addition, patients who had tumors with a DI greater than 1.6 had a significantly shorter disease-free survival than those who had tumors with a DI of less than 1.6 (P = 0.0001). After stratification by stage, this association was only seen in Dukes' stage C disease (P = 0.0065). Cox's regression analysis demonstrated that the DI (below or above 1.6) rather than DNA ploidy was an important independent predictor of disease-free survival. These results suggest that the DI rather than DNA ploidy provides us with important prognostic information in patients undergoing curative surgery for colorectal cancer. © 1993 Wiley-Liss, Inc.     

Expression of cytotoxic proteins in peripheral T-cell and natural killer-cell (NK) lymphomas: association with extranodal site, NK or Tgammadelta phenotype, anaplastic morphology and CD30 expression

Most peripheral T-cell lymphomas (PTCL) express the alphabeta T-cell receptor (TCR) whereas rare PTCL express the gammadelta TCR. Most if not all gammadelta PTCL are extranodal lymphomas and among them, hepatosplenic gammadelta PTCL constitute a distinct clinicopathological entity. Besides alphabeta and gammadelta PTCL, there is a recently recognized group of extranodal, mainly nasal tumours, which display, in most instances, phenotypic and genotypic features of Natural-Killer cell non-Hodgkin's lymphomas (NK-NHL). Cytotoxic cells, including NK cells and cytotoxic alphabeta and gammadelta T lymphocytes may induce lysis of the target by using granule-associated cytotoxic proteins such as the T-cell intracellular antigen-1 (TIA-1), perforin and granzyme B. Expression of TIA-1 can be detected in all cytotoxic cells whereas granzyme B and perforin expression can be detected in high levels only in activated cytotoxic cells. Recently, several studies showed that the expression of these cytotoxic proteins in tumour cells of PTCL and NK-NHL is associated with a) extranodal site of clinicopathological presentation b) NK or Tgammadelta-cell phenotype c) CD30 expression in cutaneous T-cell lymphoproliferations and d) anaplastic morphology in nodal PTCL. This latter finding contrasts with the data that only rare Hodgkin lymphomas (HL) express cytotoxic proteins in Hodgkin and Reed-Sternberg cells. Altogether the data of the literature indicate that most extranodal T and NK-NHL are activated cytotoxic lymphomas with the notable exception of hepatosplenic gammadelta PTCL which represent tumours of non-activated cytotoxic cells. On this basis, it is suggested that the expression of cytotoxic proteins may be useful for the identification and classification of extranodal T and NK-cell lymphomas and, to some extent, for the differential diagnosis between HL and CD30+ anaplastic large cell lymphomas. Cytotoxic lymphomas are preferentially localized in extranodal sites such as skin, lung, upper respiratory and gastrointestinal tracts, which are continuously exposed to various antigens. Since cytotoxic T and NK cells are regarded as first line of defense in these sites, and some cytotoxic tumours such as nasal lymphomas and enteropathy-type intestinal lymphomas are associated with EBV and gliadin, respectively, it is likely that chronic antigen exposure may play a role in the pathogenesis of cytotoxic lymphomas occurring in mucosa and/or skin. Besides chronic antigenic stimulation, chronic immunosuppression may also have pathogenetic significance in cytotoxic lymphomas in view of their increased incidence in immunocompromised patients.     

初诊外周T细胞淋巴瘤治疗进展

外周T细胞淋巴瘤(peripheral T-cell lymphoma,PTCL)为一组高度异质性的侵袭性非霍奇金淋巴瘤,整体预后差,目前一线治疗以CHOP(环磷酰胺+阿霉素+长春新碱+泼尼松)方案为主,但复发率较高,最近多项研究报道了初诊PTCL的治疗进展,主要涉及新的化疗方案的探索、新药联合治疗的尝试、自体干细胞移...     

The role of high-dose therapy in peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of non-Hodgkin's lymphomas. With few exceptions (eg, anaplastic large-cell lymphoma expressing the anaplastic lymphoma kinase), PTCLs have generally been reported to have a worse prognosis compared with B-cell lymphomas. Despite the poor outcome after conventional therapy, the impact of high-dose therapy with autologous or allogeneic stem cell transplantation (SCT) in these rare diseases is poorly defined mainly because of the lack of prospective PTCL-restricted studies. Most data exist for high-dose therapy with autologous SCT in relapsing or refractory disease. Because most studies showed similar results for PTCL compared with aggressive B-cell lymphomas in which high-dose therapy with autologous SCT is accepted as standard therapy, this approach seems appropriate in relapsing or refractory PTCL. Results for high-dose therapy with autologous SCT as first-line therapy mainly rely on studies on aggressive lymphomas that also included lymphomas of the T-cell phenotype. Our own recently published PTCL-restricted prospective study confirmed the feasibility with only moderate toxicity and a good response rate. Overall, patients with a good remission status after induction therapy exhibited a high complete response rate after transplantation, and at least a subgroup of patients remained in long-term remission. The greatest uncertainty exists for the impact of allogeneic SCT after high-dose therapy. In refractory or relapsing PTCL, this approach might improve the outcome for eligible patients, especially when using reduced-intensity conditioning. Overall, because data on high-dose therapy for PTCL are limited, larger and randomized studies are necessary to definitely confirm the preliminary results.     

造血干细胞移植治疗外周T 细胞淋巴瘤的进展

外周T 细胞淋巴瘤（PTCL）,其免疫表型提示来源于胸腺后（或成熟）T 细胞,包括大组非特异性PTCL。在全球范围内,PTCL约占非霍奇金淋巴瘤（NHL ）的10％,在我国约占20% ～30% ,明显高于西方国家。大多数PTCL侵袭性强,恶性程度高,传统的化疗方法与B 细胞NHL 相比疗效不佳、预后不良,５年生存率低。近年来研究表明造血干细胞移植（HSCT）对PTCL有较好的疗效,优于传统的化疗方法。本文主要总结自体造血干细胞移植（ASCT）、异基因造血干细胞移植（allo-SCT ）和自体外周血干细胞移植联合自体骨髓移植（APBHSCT+ABMT）三种方式及其优劣。ASCT无供受者之间的免疫排斥反应,造血重建快,但其复发率相对较高;allo-SCT 具有移植物抗淋巴瘤作用,但其有较高的治疗相关死亡率;APBHSCT+ABMT对于年龄偏大、造血功能差而难以采集足够外周血干细胞、有潜在出血和感染风险较大PTCL患者意义较大。HSCT的移植方法、移植时机、预处理方案及强度等多种因素对移植疗效均有影响,如何根据不同PTCL患者的具体情况选择不同的移植方式、选择合适的移植时机等问题还值得进一步深入的研究。      

Primary cutaneous non-Hodgkin's lymphoma with aggressive histology: inferior outcome is associated with peripheral T-cell type and elevated lactate dehydrogenase, but not extent of cutaneous involvement.

BACKGROUND: The aim of this study was to explore the association between extent of cutaneous involvement, presenting features and progression-free survival (PFS) in patients with primary cutaneous non-Hodgkin's lymphoma (PCNHL) of aggressive histology. METHODS: Previously untreated patients with localized or extensive PCNHL of aggressive histology, treated with combination chemotherapy, but excluding lymphoblastic lymphoma and mycosis fungoides and its variants, were reviewed retrospectively. RESULTS: We identified 53 patients, of whom 52 (35 males, 17 females) were treated with doxorubicin-based regimens. Median age was 52 years (range 25-81 years), and disease was localized and extensive in 37 and 16 patients, respectively. Twenty-four patients had diffuse large B-cell lymphoma, nine had grade 3 follicular lymphoma, 13 had peripheral T-cell lymphoma (PTCL; not otherwise specified) and seven had anaplastic large cell lymphoma (WHO classification). With a median follow-up of 101 months (range 2-237 months) for survivors, the 10-year PFS was 65 +/- 7% and overall survival was 72 +/- 8%. The first failure involved the skin in 33% of B-cell and 91% of relapsing T-cell lymphomas. Univariate analysis revealed that PTCL (P = 0.005), lymphopenia (P = 0.01) and high serum levels of beta(2)-microglobulin (P = 0.0006) and LDH (P = 0.002), but not extent of skin involvement, were associated with inferior PFS. Multivariate analysis revealed that only PTCL and high serum lactate dehydrogenase (LDH) were independently associated with inferior PFS. CONCLUSIONS: PTCL and elevated serum LDH level, but not extent of cutaneous involvement are associated with inferior PFS in aggressive PCNHL treated with combination chemotherapy.     

DNA content and prognosis of non-Hodgkin's lymphoma

Ninety cases of non-Hodgkin's lymphoma diagnosed prior to the use of modern therapeutic regimens (1963-67) and 88 cases treated with such chemotherapy (1980-85) were studied using conventional morphology and flow cytometry. DNA aneuploidy as determined by flow cytometry was more common among high grade (38%) than low grade (19%) tumours (P less than 0.01). Measurements of proliferative index (S + G2 phase cells) revealed significantly increased values for high grade as compared with low grade lymphomas (P less than 0.001). In the first group of cases (1963-67) the relationship between histological grade and survival just failed to reach statistical significance over the long term (20 yr) (P = 0.1) but proved significant over 3 yr (P = 0.012). Differences in ploidy and proliferative index status were not associated with survival. In the second patient group (1980-85) attainment of complete remission following chemotherapy was associated with the presence of DNA aneuploidy in high grade tumours (P less than 0.05). The limited follow up of this group precluded assessment of survival in relation to ploidy.