Extranodal Sites Of Disease Research Articles

The value of Ga-67 scintigraphy and F-18 fluorodeoxyglucose positron emission tomography in staging and monitoring the response of lymphoma to treatment

Gallium-67 scintigraphy (GS) has the ability to provide important diagnostic and prognostic information for the evaluation of patients with lymphoma. GS is superior to morphologic imaging techniques because of its affinity to viable lymphoma cells. The value of GS lies not in the initial diagnosis but primarily in assessing the results of treatment and in the follow-up of patients with lymphoma. Nevertheless, GS has not gained the expected wide acceptance, possibly because of the meticulous technique required and the expertise needed for optimal interpretation. The introduction of positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) as a tumor-seeking agent, which provides images of superior quality, may have an impact on the current role of GS in the management of patients with lymphoma. FDG-PET seems to share with GS the advantages of a tumor viability agent. It appears to be more sensitive for detecting nodal and extranodal sites of disease than GS and may have predictive value during and after therapy for lymphoma. These potential clinical and economic advantages of FDG-PET need to be confirmed in systematic, large-scale prospective studies.

Bulky disease is an adverse prognostic factor in patients treated with chemotherapy comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone with or without radiotherapy for aggressive lymphoma

BACKGROUND In the current study, the authors analyzed prognostic factors in patients with aggressive lymphoma treated with a chemotherapy regimen comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without radiotherapy. METHODS Between September 1988 and December 1996, 294 patients with newly diagnosed, clinical Ann Arbor Stage I-IV, aggressive lymphoma were enrolled on 2 protocols at The University of Texas M. D. Anderson Cancer Center. Patients on these studies had a relatively favorable prognosis; 100% had M. D. Anderson tumor scores ≤ 2 and 95%% had International Prognostic Indices (IPIs) ≤ 2. Treatment was comprised of 5 ± 1 (mean ± the standard deviation) cycles of CHOP chemotherapy with or without involved-field radiotherapy to a total dose of 40.1 ± 3.3 grays (mean ± the standard deviation). RESULTS The median length of follow-up was 61 months. Three factors were found to retain independent prognostic significance on multivariate analysis in terms of progression-free survival: > 1 extranodal site of disease (P < 0.001), bulky disease (≥ 7 cm) (P = 0.005), and an at least 10% elevation in the serum lactate dehydrogenase (LDH) level (P = 0.007). Patient age > 60 years (P = 0.001), bulky disease (P = 0.016), and an at least 10% elevation in the serum LDH level (P = 0.040) also were found to be independent prognostic factors for overall survival. CONCLUSIONS The independent prognostic factors in the current study suggest that either the M. D. Anderson tumor score system or the IPI can be used to select which aggressive lymphoma patients are at high risk for disease recurrence based on their having more than two adverse factors and who consequently are candidates for more intensive frontline therapy. Involved-field radiotherapy should be considered in those patients with bulky lymphomas. Cancer 2001;91:2440–60. © 2001 American Cancer Society.

Bulky disease is an adverse prognostic factor in patients treated with chemotherapy comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone with or without radiotherapy for aggressive lymphoma

In the current study, the authors analyzed prognostic factors in patients with aggressive lymphoma treated with a chemotherapy regimen comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without radiotherapy. Between September 1988 and December 1996, 294 patients with newly diagnosed, clinical Ann Arbor Stage I-IV, aggressive lymphoma were enrolled on 2 protocols at The University of Texas M. D. Anderson Cancer Center. Patients on these studies had a relatively favorable prognosis; 100% had M. D. Anderson tumor scores <or= 2 and 95%% had International Prognostic Indices (IPIs) <or= 2. Treatment was comprised of 5 +/- 1 (mean +/- the standard deviation) cycles of CHOP chemotherapy with or without involved-field radiotherapy to a total dose of 40.1 +/- 3.3 grays (mean +/- the standard deviation). The median length of follow-up was 61 months. Three factors were found to retain independent prognostic significance on multivariate analysis in terms of progression-free survival: > 1 extranodal site of disease (P < 0.001), bulky disease (>or= 7 cm) (P = 0.005), and an at least 10% elevation in the serum lactate dehydrogenase (LDH) level (P = 0.007). Patient age > 60 years (P = 0.001), bulky disease (P = 0.016), and an at least 10% elevation in the serum LDH level (P = 0.040) also were found to be independent prognostic factors for overall survival. The independent prognostic factors in the current study suggest that either the M. D. Anderson tumor score system or the IPI can be used to select which aggressive lymphoma patients are at high risk for disease recurrence based on their having more than two adverse factors and who consequently are candidates for more intensive frontline therapy. Involved-field radiotherapy should be considered in those patients with bulky lymphomas.

Dose-response analysis for radiotherapy delivered to patients with intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to CHOP-based induction chemotherapy

Purpose: To test the hypothesis that prechemotherapy tumor size affects the dose of radiation that should be delivered to intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-based induction chemotherapy. Methods and Materials: From September 1988 through December 1996, 294 patients with newly diagnosed, Stage I–IV, intermediate-grade or large-cell immunoblastic lymphomas were enrolled on 2 prospective protocols at the M. D. Anderson Cancer Center. Treatment consisted of CHOP-based chemotherapy with or without involved field radiotherapy. One hundred seventy-two patients, with 178 nodal sites and 87 nonbony, extranodal sites of disease achieved a complete response to 2–6 cycles of chemotherapy and underwent involved field radiotherapy. Total radiation doses ranged from 30.0 to 50.4 Gy (mean ± standard deviation: 39.7 ± 2.5 Gy) over 22–49 days using a daily fraction size of 1.3–2.3 Gy. Because various fraction sizes were delivered, the linear-quadratic model was used to convert total radiation doses to biologically equivalent doses given at 1.8 Gy per fraction (D1.8). An α/β ratio of 10 Gy was used for the lymphomas, resulting in D1.8 ranging from 29.1 to 50.8 Gy. Regression tree analysis was performed on nodal sites of disease to determine which of the following factors were predictive of local control: age, tumor size, D1.8, total radiation dose, and duration of radiotherapy. Based on the results of the regression tree analysis, Kaplan-Meier analysis was used to determine the probability of local control per site as a function of tumor size and D1.8. Regression tree analysis was also performed on patients with nonbony disease who received D1.8 = 29.1–39.1 Gy to determine if small lymphomas could be locally controlled with relatively low doses of radiation. The log-rank test was used to compare local control curves. Results: The median length of follow-up among survivors was 63 months. Regression tree analysis of nodal sites identified 3 distinct groups: (a) lymphomas ≤ 10 cm and D1.8 = 29.1–39.1 Gy; (b) lymphomas ≤ 10 cm and D1.8 = 39.2–50.8 Gy; and (c) lymphomas > 10 cm. For nonbony lymphomas that measured < 3.5 cm, low doses of radiation resulted in excellent local control (5-year rates: 96% vs. 97% for D1.8 = 29.1–39.1 Gy vs. D1.8 = 39.2–50.8 Gy; p = 0.610). For 3.5–10.0 cm lymphomas, higher doses of radiation resulted in better local control (5-year rates: 40% versus 98% for D1.8 = 29.1–39.1 Gy versus D1.8 = 39.2–50.8 Gy, p < 0.0001). A narrow dose range (D1.8 = 39.2–40.7 Gy) was delivered to the 8 lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, resulting in a 5-year local control rate of only 70%. There was no difference in local control for nodal versus nonbony, extranodal sites of disease. Conclusion: D1.8 ranging from 29.1 to 39.1 Gy yielded excellent local control for nonbony lymphomas measuring < 3.5 cm that had completely responded to a median of 3 cycles of CHOP-based chemotherapy. D1.8 ranging from 39.2 to 50.8 Gy yielded excellent local control for nonbony lymphomas measuring 3.5–10.0 cm that completely responded to either 3 or 6 cycles of chemotherapy. For nonbony lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, D1.8 ranging from 39.2 to 40.7 Gy yielded suboptimal local control, suggesting that higher doses of radiation are indicated.

High-dose therapy with peripheral blood stem cell transplantation for patients with relapsed or refractory Hodgkin's disease: long-term outcome and prognostic factors.

From March 1986 to March 1998, 82 patients with relapsed or refractory Hodgkin's disease underwent high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) transplantation in our center. This is a retrospective analysis of the long-term clinical outcome. There were 52 males and 30 females with a median age of 32 years (range 18-59 years). Prior to transplantation, 36 patients were in complete remission (CR), 34 in partial remission (PR), and 12 had refractory disease after salvage therapy. For HDCT, 78 patients were treated with CBV (cyclophosphamide, 6.0-6.8 g/ m2; etoposide, 1.0-1.6 g/m2; carmustine, 0.45-0.8 g/m2), while four patients received different regimens. Probability of freedom from progression (FFP), overall survival (OS), and event-free survival (EFS) at 5 years of the entire group was 63%, 61%, and 54%, respectively. Early mortality rate ( < or = 100 days) declined from 17% to 6% after 1992. Five patients died of late transplant-related complications (> 100 days), including secondary lymphoma and leukemia in two patients. None of the refractory patients survived beyond 3.5 years. Multivariate analyses identified extranodal sites of disease at relapse and refractory disease status prior to transplantation as significant prognostic factors for FFP, EFS, and OS. As we have shown in our study, remarkable progress was achieved in reducing early morbidity and mortality over time, but this was associated with only a slight, not significant improvement of long-term outcome (OS 66% vs 57% at 5 years for patients undergoing PBSC transplantation before and after 1992, P = 0.26). Although the results as a whole are encouraging for chemosensitive patients, new therapeutic strategies are needed to reduce toxicity and improve the clinical outcome of patients, especially of those with a less favorable prognosis.

High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis

High-dose chemoradiotherapy (HDT) with autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, its role in the treatment of patients with primary refractory disease is not well defined. The outcomes of 85 patients with primary refractory aggressive NHL who underwent second-line chemotherapy with ICE with the intent of administering HDT/ASCT to those patients with chemosensitive disease were reviewed. Patients were retrospectively classified as induction partial responders (IPR) if they attained a partial response to doxorubicin-based front-line therapy or as induction failures (IF) if they had less than partial response. Forty-three patients (50.6%) had ICE-chemosensitive disease; there was no difference in the response rate between the IPR and the IF groups. Intention-to-treat analysis revealed that 25% of the patients were alive and 21.9% were event-free at a median follow-up of 35 months. Among 42 patients who underwent transplantation, the 3-year overall and event-free survival rates were 52.5% and 44.2%, respectively, similar to the outcomes for patients with chemosensitive relapsed disease. No differences were observed between the IPR and IF groups, and there were no transplantation-related deaths. More than one extranodal site of disease and a second-line age-adjusted International Prognostic Index of 3 or 4 before ICE chemotherapy were predictive of poor survival. These results suggest that patients with primary refractory aggressive NHL should receive second-line chemotherapy, with the intent of administering HDT/ASCT to those with chemosensitive disease. Newer therapies are needed to improve the outcomes of patients with poor-risk primary refractory disease.

High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis

AbstractHigh-dose chemoradiotherapy (HDT) with autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, its role in the treatment of patients with primary refractory disease is not well defined. The outcomes of 85 patients with primary refractory aggressive NHL who underwent second-line chemotherapy with ICE with the intent of administering HDT/ASCT to those patients with chemosensitive disease were reviewed. Patients were retrospectively classified as induction partial responders (IPR) if they attained a partial response to doxorubicin-based front-line therapy or as induction failures (IF) if they had less than partial response. Forty-three patients (50.6%) had ICE-chemosensitive disease; there was no difference in the response rate between the IPR and the IF groups. Intention-to-treat analysis revealed that 25% of the patients were alive and 21.9% were event-free at a median follow-up of 35 months. Among 42 patients who underwent transplantation, the 3-year overall and event-free survival rates were 52.5% and 44.2%, respectively, similar to the outcomes for patients with chemosensitive relapsed disease. No differences were observed between the IPR and IF groups, and there were no transplantation-related deaths. More than one extranodal site of disease and a second-line age-adjusted International Prognostic Index of 3 or 4 before ICE chemotherapy were predictive of poor survival. These results suggest that patients with primary refractory aggressive NHL should receive second-line chemotherapy, with the intent of administering HDT/ASCT to those with chemosensitive disease. Newer therapies are needed to improve the outcomes of patients with poor-risk primary refractory disease.

Prognostic Significance of Anaplastic Lymphoma Kinase (ALK) Protein Expression in Adults With Anaplastic Large Cell Lymphoma

Anaplastic large cell lymphoma (ALCL) is an aggressive lymphoma that is frequently associated with the t(2;5)(p23;q35), resulting in expression of a fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which can be detected by either monoclonal or polyclonal antibodies to the ALK protein. The clinical features of adults with ALCL are incompletely described, and the prognostic factors that are useful for predicting survival remain unclear. This report describes the clinical and laboratory findings in 70 adults with systemic ALCL who were treated with curative intent. We attempted to identify the clinical and pathological factors of prognostic importance, including the International Prognostic Index (IPI), immunophenotype, and expression of the ALK protein. The median age of the patients was 49 years (range, 15 to 75). There were 26 women and 44 men with a median follow-up of 50 months for living patients. Advanced stage was present in 56% and B symptoms were noted in 70% of the patients. Immunostains showed that 46% of the cases had a T-cell phenotype, 36% a null phenotype, and 18% a B-cell phenotype. The expression of ALK protein was found in 51% of the cases. The IPI factors were evenly distributed between the ALK+ and ALK- groups, except that the ALK+ patients were younger (median age, 30 v 61 years; P <.002). The ALK+ cohort included cases with null (44%), T-cell (42%), and B-cell (14%) phenotypes. All 10 cases with cytogenetic or molecular evidence of a t(2;5) were ALK+. The 5-year overall survival (OS) of the entire cohort was 65%. The 5-year OS of the ALK+ and ALK- cases was 79% and 46%, respectively (P <.0003). Analysis of only the T-cell/null cases (n = 57) showed a 5-year OS of 93% for the ALK+ cases and only 37% for the ALK- cases (P <.00001). Univariate analysis of the clinical features showed that age </=60 years (P <.007), a normal serum lactate dehydrogenase (LDH) (P <.00001), a good performance status (Eastern Cooperative Oncology Group [ECOG] <2) (P <.03), </=1 extranodal site of disease (P <.012), and an IPI score </=3 (P <.00001) were associated with improved OS. Although a younger age correlated with ALK positivity, multivariate analysis showed that only a normal serum LDH (P <. 00001), an IPI score of </=3 (P <.0005), and ALK protein expression (P <.005) predicted independently for an improved OS. We conclude that ALCL is a heterogeneous disorder. However, ALK protein expression is an independent predictor of survival and serves as a useful biologic marker of a specific disease entity within the spectrum of ALCL.

Prognostic Significance of Anaplastic Lymphoma Kinase (ALK) Protein Expression in Adults With Anaplastic Large Cell Lymphoma

AbstractAnaplastic large cell lymphoma (ALCL) is an aggressive lymphoma that is frequently associated with the t(2;5)(p23;q35), resulting in expression of a fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which can be detected by either monoclonal or polyclonal antibodies to the ALK protein. The clinical features of adults with ALCL are incompletely described, and the prognostic factors that are useful for predicting survival remain unclear. This report describes the clinical and laboratory findings in 70 adults with systemic ALCL who were treated with curative intent. We attempted to identify the clinical and pathological factors of prognostic importance, including the International Prognostic Index (IPI), immunophenotype, and expression of the ALK protein. The median age of the patients was 49 years (range, 15 to 75). There were 26 women and 44 men with a median follow-up of 50 months for living patients. Advanced stage was present in 56% and B symptoms were noted in 70% of the patients. Immunostains showed that 46% of the cases had a T-cell phenotype, 36% a null phenotype, and 18% a B-cell phenotype. The expression of ALK protein was found in 51% of the cases. The IPI factors were evenly distributed between the ALK+ and ALK− groups, except that the ALK+ patients were younger (median age, 30 v 61 years; P < .002). The ALK+ cohort included cases with null (44%), T-cell (42%), and B-cell (14%) phenotypes. All 10 cases with cytogenetic or molecular evidence of a t(2;5) were ALK+. The 5-year overall survival (OS) of the entire cohort was 65%. The 5-year OS of the ALK+ and ALK− cases was 79% and 46%, respectively (P < .0003). Analysis of only the T-cell/null cases (n = 57) showed a 5-year OS of 93% for the ALK+ cases and only 37% for the ALK− cases (P < .00001). Univariate analysis of the clinical features showed that age ≤60 years (P < .007), a normal serum lactate dehydrogenase (LDH) (P < .00001), a good performance status (Eastern Cooperative Oncology Group [ECOG] <2) (P< .03), ≤1 extranodal site of disease (P < .012), and an IPI score ≤3 (P < .00001) were associated with improved OS. Although a younger age correlated with ALK positivity, multivariate analysis showed that only a normal serum LDH (P < .00001), an IPI score of ≤3 (P < .0005), and ALK protein expression (P < .005) predicted independently for an improved OS. We conclude that ALCL is a heterogeneous disorder. However, ALK protein expression is an independent predictor of survival and serves as a useful biologic marker of a specific disease entity within the spectrum of ALCL.

The role of radiotherapy in the treatment of localised intermediate and high grade non-Hodgkin's lymphoma in elderly patients

Background and purpose: The treatment of elderly patients with high or intermediate grade non-Hodgkin's lymphoma (NHL) remains difficult and controversial. In order to audit our own practice, 270 elderly patients treated between 1988 and 1993 with this diagnosis were retrospectively reviewed. Material and methods: 81 patients unfit for chemotherapy received fractionated radiotherapy for apparently localised stage I or II disease. The median age of the patients was 78 years (range 70–87 years). Forty stage I and 17 stage II patients had extra-nodal sites of disease. The radiation field included the primary site plus immediate adjacent nodes. Results: After a median follow-up of 3.9 years the 5-year overall and disease-free survival rates were 33% and 31%, respectively. Age (hazard ratio (HR) 1.22, P=0.03), stage (HR 5.50, P=0.02) and lactate dehydrogenase level (HR 1.003, P=0.004) were identified as independent risk factors for relapse. Conclusion: These factors can define a group in which radiotherapy can produce acceptable survival rates (age≤80 years, stage I and lactate dehydrogenase≤500). This group represented 34% of those patients where all these variables were recorded and had 5-year disease-free and overall survival rates of 56% and 62%, respectively.

BONE MARROW (BM) INVOLVEMENT IN AIDS-LYMPHOMA (AIDS-NHL): CLINICAL, IMMUNOLOGIC AND PATHOLOGIC FEATURES.

85 Background: Marrow involvement is reported in approximately 25% of patients (pts) with AIDS-NHL at dx. We report characteristics of marrow involvement in 41 such HIV+ pts. Methods: Retrospective review of all newly diagnosed patients with AIDS-NHL BM biopsies positive for NHL, seen at a single institution between 1984-97. Results: Pts included 40 males and 1 female, with a median age of 37 yrs (25-64). There were 22 Caucasians (54%), 14 (34%) Hispanics, 3 African Americans, and 2 Asians. Fourteen (34%) reported history of AIDS prior to NHL diagnosis. Median CD4 count was 129/mm3 (range 12-1927), and 66% had CD4 counts < 200/mm3. T cell lymphoma was diagnosed in 4 (10%), including 2 T-immunoblastic, 1 anaplastic large cell, and 1 peripheral T cell. 37 (90%) were B cell lymphomas, including 3 with low grade NHL, and the remainder with high or intermediate grade lymphoma, including small non-cleaved in 24 (58%) immunoblastic in 6 (20%), diffuse large cell in 4 (10%). Clinically, systemic "B" symptoms were present in 30 (73%). Other sites of extra-nodal disease included liver in 14 (34%); spinal fluid in 10 (24%), and GI tract in 5 (12%). Lab evaluation at diagnosis revealed a median hemoglobin of 10.6 gm/dl (range 6.3-17), with 41% (16/39) presenting with Hb<10; median WBC was 4.85/mm3 (range 1.9-15.6) with 10 (24%) demonstrating WBC < 4000. Median platelet count was 185,000/mm3 (range 2-504), with 18% demonstrating a platelet < 100,000. Notably, LDH was elevated in 33 (85%); 17 pts had an LDH > 1000. The majority of pts received CHOP (n=16) or mBACOD (n=13) regimens, and 4 were not treated. Median survival was 5.8 months (range 0.2-11.1+ yrs). 9 pts have survived more than 1 year. 2 low grade NHL are alive at 11+ and 11.1+ yrs. Pts with thrombocytopenia had significantly poorer survival (median 1.9 mos versus 6.4 mos, p=0.005); presence of leukopenia or anemia had no impact on survival (p>0.05). Conclusions: (1) The majority of pts with AIDS-NHL and marrow involvement do not present with cytopenias in the peripheral blood; (2) anemia is the most frequent abnormality encountered; (3) pts with thrombocytopenia have poor prognosis; (4) approximately 25% have simultaneous involvement of cerebrospinal fluid; (5) long term survival is possible in HIV+ pts with low grade lymphoma, involving marrow.

Results of Treatment with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) for Non-Hodgkin’s Aggressive Lymphoma Analyzed According to the International Prognostic Index

Forty patients with aggressive (intermediate-grade and high-grade) non-Hodgkin’s lymphoma (NHL) were treated primarily with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen, and then evaluated for prognostic features. Age, tumor stage, performance status, number of extranodal disease sites and serum concentrations of lactate dehydrogenase (LDH) were considered prognostic features. All the patients treated with the CHOP regimen were grouped into four risk categories, including low (L), low-intermediate (LI), high-intermediate (HI) and high (H) according to the International Prognostic Index. Twenty-one of 23 patients (91.3%) in the L plus LI risk groups and 5 of 17 patients (29.4%) in the H plus HI risk groups had complete response and the difference between these percentages was statistically significant (P<0.001). The overall survival rate (2 yr) of 23 patients in the L+LI risk group was 52.1% and of 17 patients in H+HI risk group was 11.7% and this difference was statistically significant (P<0.05). Our results indicated that the CHOP regimen is not effective in the HI+H risk groups of patients with aggressive NHL. New experimental approaches are needed for these patients.

The radiology of non-Hodgkin's lymphoma in childhood: A review of 80 cases

The clinical spectrum of childhood non-Hodgkin's lymphoma (NHL) is different from that in adults, with frequent extranodal involvement. CT scanning as part of routine staging appears to show more frequent sites of extranodal disease than were previously recognized. We have reviewed the CT and other radiological findings in 80 children with NHL to document the incidence and radiological appearance of visceral involvement, to compare this with the pattern of adult disease, and to assess how frequently clinical stage of disease was altered by radiological findings. The age of the children ranged from 9 months to 17 years 4 months (mean 9 years 2 months). The presenting site was in the abdomen in 21 (27%), extranodal sites in the head and neck in 18 (23%), mediastinum in 16 (20%), peripheral lymph nodes in 15 (19%), pelvic organs in four, skin in four, and bone in two. Fifteen children had gastrointestinal lymphoma, the majority involving the ileocaecal junction. The kidneys were involved in 10 children, the pancreas in three; no child with renal or pancreatic involvement had associated retroperitoneal lymph node enlargement. Eight children had bone involvement and only two of the 80 children had pulmonary nodules at presentation. In this series, of the 44 children who had CT of the chest and abdomen, only five had stage of disease increased as a result, three with the primary disease in peripheral lymph nodes, and two with the primary disease in extranodal sites in the head and neck.

High incidence of lymphoid infiltration on labial salivary gland biopsy in non‐Hodgkin's lymphomas: clinical implications

Sjögren's syndrome (SS) is characterized by an increased risk of developing a non-Hodgkin's lymphoma (NHL). We performed labial salivary gland biopsy (LSGB) in 103 patients with untreated NHL, negative for human immunodeficiency virus. Median age was 58 years (range 21-79) and M/F 1.3. Using the Working Formulation, 37 patients had low-grade NHL and 66 had intermediate- or high-grade NHL. Dense lymphocytic infiltration (positive focus score 3 or 4) was found in 28 patients. 10 (35%) of these 28 patients fulfilled criteria for possible SS. 15/28 patients had an identical monotypic infiltrate on LSGB and NHL tissue (including two of the 10 patients with criteria for SS). The significance of the lymphoid infiltrate of LSGB was unknown in the five remaining patients with positive focus score. Significant correlations were found between positive focus score and presence of two or more extranodal sites of disease (P = 0.02), impaired performance status (P = 0.004), splenomegaly (P = 0.05), increased gammaglobulin level (P = 0.03), and beta 2 microglobulin (P = 0.004). Considering intermediate- or high-grade NHL, we found significant correlation between positive focus score and unfavourable prognosis according to the two Dana Farber Cancer Institute indexes (P < 0.04), to the LNH-84 index (P = 0.05), and to the international index (P = 0.003). In conclusion, systematic evaluation of LSGB in 103 patients with NHL found lymphoid infiltration in 28% of them, but possible SS could be considered in only 10%. This lymphoid infiltration, though not correlated with any particular histological subtypes, was associated with unfavourable clinical prognostic factors, especially in intermediate- or high-grade NHL.

Long-term outcome of follicular low-grade lymphoma a report of 91 patients

We retrospectively analyzed overall survival and survival after progression in 91 patients with low-grade follicular lymphoma (LGFL). Histological subtype was B in 75 patients and C in 16 patients. Twelve patients with localized disease received involved-field radiotherapy; seven patients without bulky disease had no initial therapy. The remaining 72 patients received long-term chlorambucil (9 patients), MOPP or COPBleo (42 patients), or a CHOP-derived regimen (21 patients). Forty-two patients (46%) achieved a complete remission (CR) and 28 patients (31%) achieved a partial remission; 48 of these 70 patients relapsed or progressed. Nineteen of the other 21 patients with stable LGFL progressed. Two other patients failed to respond and rapidly died. Thirty-two of the 67 patients with progressive or relapsed LGFL have died. Median overall survival was 111 months. Age > or = 70 years, male sex, B symptoms, histological subtype follicular mixed-cell NHL, tumor size > or = 10 cm, number of extranodal sites of disease > or = 2, pleural effusion, and Ann Arbor stage III or IV were found to adversely influence overall survival. Failure-free survival < 24 months, failure to achieve a CR after the progression, initial histological subtype follicular mixed cell, initial Ann Arbor stage III or IV, and initial tumoral size > or = 10 cm were found to adversely influence survival after progression. Our results suggest that most prognostic factors for overall survival in LGFL are related to histological subtype or tumor burden. Some initial adverse prognostic factors for survival may be also associated with a poor survival after progression.

Beta-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin's lymphomas.

beta-2 microglobulin levels were measured in stored serum taken at presentation from 262 patients treated with combination chemotherapy for Kiel classification high-grade lymphoma at a single centre over a 15 year period. A significant association was found between elevated levels and advanced (Ann Arbor stage III or IV) disease or hepatic infiltration, but not with other sites of extranodal involvement or bulky disease. Patients with normal levels at presentation had a 70% remission rate with treatment compared to 37% of those with elevated levels (P < 0.001). With median follow up of 6 years duration of remission was significantly greater in patients with normal beta-2 microglobulin at presentation (plateau at 70%, compared to median remission of 19 months in those with raised levels, P < 0.001). Survival overall was also better in the group with normal levels (actuarial median 9 years compared to 1 year, P < 0.001). Multivariate analyses including treatment type, age, sex, B symptoms, stage, bulk, albumin, sodium, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and beta-2 microglobulin, placed beta-2 microglobulin among the three most influential independent variables for prediction of response rate, duration of remission and overall survival.

Prognosis and treatment of lymphoblastic lymphoma in adults: a report on 80 patients.

We analyzed prognostic factors in 80 adult patients with lymphoblastic lymphoma (LBL). Twenty-one patients received six monthly courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and maintenance chemotherapy for 12 months. The LNH-84 protocol (30 patients) consisted of four courses of high-dose CHOP followed by consolidation for 4 months. Both FRALLE (22 patients) and LALA (seven patients) protocols were two intensive chemotherapy regimens for acute lymphoblastic leukemia (ALL) that included an induction with daunorubicin, vincristine, cyclophosphamide, prednisolone (and asparaginase for the FRALLE regimen), consolidation, and maintenance chemotherapy that lasted for 2 years. Sixty-six patients (82%) achieved a complete remission (CR). The CR duration rate and overall survival rate at 30 months were estimated to be 46% and 51%, respectively, with a median follow-up of 55 months. Only two of 37 relapses occurred after 26 months. Chemotherapy protocol did not influence CR rate, CR duration, and survival. A higher CR rate was associated with an age of less than 40 years, lactic dehydrogenase (LDH) level of less than two times the upper limits of normal, and no or one extranodal site of disease. Short survival was associated with a failure to achieve CR, age older than 40 years, B symptoms, LDH level more than two times the upper limits of normal, and hemoglobin level of less than 100 g/L. Bone marrow involvement had no prognostic value. We could not evaluate precisely the prognostic value of Ann Arbor stage because inclusion criteria differed among treatment groups. Our findings suggest that age and LDH are two important pretreatment prognostic factors for adult LBL, and that the optimal prognostic staging system remains a controversial issue.

Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-hodgkin's lymphoma

A novel chemotherapeutic approach was designed for the treatment of intermediate and high-grade histology non-Hodgkin's lymphoma using augmented (but subtransplantation) doses of chemotherapy administered at frequent intervals in the inpatient setting. For the initial evaluation of this regimen, poor prognosis patients were treated with a projected long-term survival rate of less than 25% in response to standard therapy. Between March 1982 and May 1988, 56 previously untreated patients were entered into this study; all patients had either high-grade histology (20 patients) or predominantly large cell lymphoma (36 patients). Median age was 41.5 years (range, 18 to 69 years). Poor prognosis features included: Stage IV, 71%; poor performance status (Eastern Cooperative Oncology Group scale, 2 to 4), 55%; multiple extranodal sites of disease, 52%; elevated lactic dehydrogenase (greater than 300 IU/l), 43%; and bulky (greater than 10 cm) tumor masses, 30%. Thirty-three of 56 patients (59%) were in Shipp's Category 3. During the 6-year study, the chemotherapy regimen was modified in an attempt to improve efficacy and reduce toxicity. However, most patients received a 2-month course of therapy as follows: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1, 2, and 29; etoposide 400 mg/m2 IV on days 1, 2, and 3 and 100 mg/m2 on days 29, 30, 31; doxorubicin 45 mg/m2 IV on days 29, 30; vincristine 1.4 mg/m2 IV on days 8, 22, 36, and 50; bleomycin 10 units/m2 IV on days 8, 22, 36, and 50; methotrexate 200 mg/m2 IV on days 15 and 43 followed 24 hours later by leucovorin 15 mg/m2 IV every 6 hours for six doses; and prednisone 60 mg/m2 orally on days 1 to 7 and 29 to 35. The complete response (CR) rate was 77% (95% confidence interval, 64% to 86%). There were ten relapses, only one of which occurred after 18 months of follow-up. Overall event-free survival (EFS) was 52% (95% confidence interval, 36% to 68%), with a median follow-up of 36 months. Eleven of 13 patients with small noncleaved lymphoma had CR; actuarial EFS in this subgroup was 61%. Myelosuppression occurred in all patients, with severe leukopenia (less than 1000/microliters) lasting a median of 12 days (range, 3 to 29 days); toxic deaths occurred in five patients (9%; 95% confidence interval, 4% to 19%). This intensive approach improved the response and survival of very poor risk non-Hodgkin's lymphoma patients.

Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse.

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.

MACOP-B and VACOP-B in diffuse large cell lymphomas and MOPP/ABV in Hodgkin's disease

Between 1981 and 1986, 126 patients with diffuse large cell lymphoma were treated with MACOP-B (methotrexate/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomy cin). All had advanced-stage lymphoma (Ann Arbor stage III or IV or stage I or II if the tumor mass was greater than 10 cm or B symptoms were present). The complete response (CR) rate was 84% and the toxic death rate was 6%. Actuarial overall survival at 3 years was 67% and at 8 years 62%; the failure-free survival at 8 years was 52%. The follow-up for MACOP-B is 39 to 106 months (median 76) for living patients. A multivariate prognostic factor analysis for this group of patients identified age greater than 60 years. B symptoms, more than one extranodal site of disease, and more than three nodal sites of disease as the four significant prognostic variables. From June 1986, 108 patients were enrolled on a modification of MACOP-B called VACOP-B (etoposide/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomycin ). Their CR rate was 81%, and the toxic death rate was lower, at 3%. The 60% overall survival at 3 years is not statistically significantly different from that of MACOP-B. The incidence of moderate or severe mucositis and Cushingoid changes was much lower with VACOP-B. The MOPP/ABV (mechlorethamine/vincristine/procarbazine/prednisone- doxorubicin/bleomycin/vinblastine) hybrid chemotherapy regimen for advanced-stage Hodgkin's disease was standard therapy from April 1981 to June 1988 for untreated patients aged 16 to 65. Advanced stage was defined as stages IIB, IIIB, III2A, IVA, IVB, or stages IIA or IIIA with greater than four splenic nodules or a mediastinal mass greater than one third of the transthoracic diameter.(ABSTRACT TRUNCATED AT 250 WORDS)