Prognostic significance of the standardized uptake value of pre-therapeutic <Superscript>18</Superscript>F-FDG PET in patients with malignant lymphoma

Metabolic imaging with F-18-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography (PET) is widely used for staging and treatment evaluation of malignant lymphoma. To date, only a few studies have indicated that lower glucose metabolism measured by ¹⁸F-FDG PET before or early in the course of treatment of malignant lymphoma is associated with a favorable outcome. The aim of this study was to assess the prognostic capability of the ¹⁸F-FDG PET maximum standardized uptake value (SUV_max), a semiquantitative measurement of glucose metabolism, at the time of diagnosis of malignant lymphoma. We retrospectively analyzed data from 69 patients (median age: 61 and range 23–80) with malignant lymphoma (22 patients with Hodgkin’s disease [HD] and 47 patients with Non-Hodgkin’s lymphoma [NHL]) who had not received treatment before ¹⁸F-FDG PET imaging. Metabolic remission according to PET results was observed after chemotherapy in 50 patients (72.5%), while progressive disease or relapse was diagnosed in 19 patients (27.5%). Clinical follow-up revealed relapse in 4/50 patients with prior metabolic remission. A significantly lower (P < 0.01) baseline SUV_max level (median: 4.6 and range 1.5–12.9) was found in patients with subsequent metabolic and clinical response than in those with progressive or relapsing disease (median SUV_max 10.4, range 2.0–17.9). Thirty-seven of thirty-nine patients with baseline SUV_max < 7.4 achieved long-lasting remission after completion of chemotherapy (median follow-up: 28 months, range 4–112 months). Within this group with favorable outcome, there were no significant differences between SUV_max values in HD and NHL. A heterogeneous outcome was noted in 25 patients with a SUV_max ≥ 7.4 and ≤ 12.9 at diagnosis, with 16 patients experiencing disease progression or relapse and nine patients extended remission. The five patients with SUV_max > 12.9 showed disease progression at follow-up. Semiquantitative measurement of glucose metabolism (SUV_max) by ¹⁸F-FDG PET at diagnosis is a predictor of outcome of patients with malignant lymphoma.     

Phase II study of 9-aminocamptothecin in previously treated lymphomas: results of Cancer and Leukemia Group B 9551

Purpose  To evaluate the efficacy and toxicity of the topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), in patients with relapsed lymphoma and to correlate 9-AC plasma concentrations with response and toxicity. Methods  Eligible patients had relapsed Hodgkin lymphoma (HL) treated with one or two prior regimens, low grade non-Hodgkin’s lymphoma (NHL) treated with one or two prior regimens, or aggressive NHL treated with one prior regimen. The first nine patients received 9-AC dimethylacetamide 0.85 mg/m² per day intravenously over 72 h every 2 weeks and the remaining 27 patients received 9-AC/colloidal dispersion 1.1 mg/m² per day. Patients received a minimum of three cycles unless progression or intolerable toxicity occurred. Responding patients received two cycles past best response with a minimum of six cycles. Results  CALGB 9551 accrued 37 patients from April 1996 through October 2000; one patient with HD, 18 patients with indolent lymphoma, and 17 patients with aggressive lymphoma. The overall response rate was 17%, with response rates of 11% (2 partial responses) in patients with indolent histologies and 23% (1 complete response, 3 partial responses) in patients with aggressive histologies. The patient with HD did not respond. Response rates were similar for both drug formulations. The median remission duration for the six responders was 6.5 months, with one remission lasting longer than 12 months. Significant grade 3 and 4 toxicities included neutropenia (66%), anemia (31%), and thrombocytopenia (36%), with 20% of patients experiencing grade 3 or 4 infection. No treatment related deaths occurred. Steady state serum concentrations did not correlate with patient response or toxicity. Conclusion  Single agent 9-AC has modest activity in aggressive non-Hodgkin’s lymphomas.     

The monocyte tumor necrosis factor-alpha production in patients with acute leukemia in complete remission

Tumor necrosis factor-α (TNF-α) production by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral monocytes has been studied in 17 acute myeioid leukemia (AML) patients, 54 AML patients in complete remission (AML-CR), 9 acute lymphoblastic leukemia (ALL) patients and 13 ALL patients in complete remission (ALL-CR). TNF-α production by the unstimulated monocytes in ALL patients (n - 6, mean: 6.6 ± 4.9 u/ml) was higher than that of normal controls (n = 13, 0.9 ± 0.7 u/ml), AML patients (n = 14, 2.0 ± 2.1 u/ml) and AMLCR patients (n = 21,1.4 ± 1.2 u/ml). TNF-α production by the LPS-stimulated monocytes of the AML-CR patients (n = 54,12.4 ± 13.4 u/ml) was significantly higher than that of the normal controls (n = 21, 3.5 ± 2.5 u/ml) and the AML patients (n = 17, 2.6 ± 2.4 u/ml),p < 0.01, but there were not any significant differences among the AML-CR patients and the ALL patients or the ALL-CR patients. We separated the AML-CR patients into 3 groups, depending on the length of their remission, and found that AML-CR patients with longer than 6 months (M) but less than 60 M (n = 21,15.7 ± 16.9 u/ml) and the patients with a remission longer than 60 M (n = 11,18.2 ± 15.9 u/ml) had significantly higher TNF-α production than that of the controls.     

High-dose therapy with autologous haematopoietic support in patients with transformed follicular lymphoma: A study of 27 patients from a single centre

Background: The prognosis of patients with transformed follicular lymphoma (FL-t) is poor. The use of high-dose therapy (HDT) with autologous haematopoietic support was therefore evaluated as consolidation of remission.Patients and methods: Twenty-seven patients received high-dose cyclophosphamide and total body irradiation (cyclo + TBI) with autologous bone marrow (BM; n = 24) or peripheral blood progenitor cell support (PBPC; n = 3). BM was treated in vitro with anti-B cell antibodies and complement. Nineteen of 27 patients were treated in first stable remission following transformation. Eight other patients with a history of transformation were treated following a subsequent recurrence of follicular lymphoma (FL).Results: With a median follow-up of 2.4 years, 14 of 27 patients remain alive and in remission; five are alive and free of disease at more than four years. The median survival is 8.5 years. There were two early treatment-related deaths of respiratory failure, and two late deaths of myelodysplastic syndrome (MDS) in remission of lymphoma at 2.8 and 8.5 years.Seven of nine patients having had a recurrence underwent re-biopsy. In two, histology revealed FL, in five, transformed follicular lymphoma. One of the patients with recurrent FL is alive without further therapy, and two of five patients with recurrent FL-t are alive and in remission after further chemotherapy.Conclusions: It is appropriate to consider HDT for younger patients with FL-t in remission. Repeat biopsy should be considered for patients with recurrent disease. There is a risk of late MDS in patients undergoing this treatment.     

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR LYMPHOMA： AN EVALUATION OF GRAFTS SOURCE AND MINIMAL RESIDUAL DISEASE

High-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) has significantly improved the prognosis of lymphomas[1]. Some studies have demonstrated an improved outcome for patients with high-risk aggressive NHL who receive autologoustransplantation in first remission[2]. The benefits of mobilized peripheral blood stem cell transplantation (PBSCT) have been demonstrated over the past decade, the use of autologous bone marrow as a graft source has diminished substantia…     

Cytosine Arabinoside and Etoposide (CARE) in relapsed and refractory non-hodgkin’s Lymphoma

Twelve patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL) were treated with a 5 day protocol of high dose cytosine arabinoside 3g/m² and etoposide 200mg/m² (CARE) daily for 4 days for either 1 or 2 cycles together with alternating intrathecal cytosine arabinoside and methotrexate. Seven men and 5 women aged 18 to 65 years (median age 47.5 years) have received a total of 19 cycles. Six patients had Stage III and 6 had Stage IV disease, all with marrow involvement. Three patients had diffuse small lymphocytic NHL, 3 had diffuse large cell NHL, 3 had diffuse small cleaved NHL and 3 remaining patients had diffuse mixed small and large cell NHL, lymphoblastic NHL and Burkitt’s. Six patients (50%) achieved complete remission (3-44 months), four of whom subsequently underwent successful autologous bone marrow transplantation and a fifth has had marrow harvested in preparation for ABMT. One patient achieved partial remission and 5 patients had no response to CARE. Ten patients had nadir granulocyte counts less than 0.5xl0⁹/1 and all required red cell (range 2-11 units) and platelet (range 6-130 units) transfusions. The platelet nadir was less than 20x10⁹ /1 in all patients. One patient with refractory disease succumbed to pulmonary haemorrhage while three other patients developed reversible toxicity with severe mucositis, prolonged diarrhoea and acute renal failure. One patient with refractory disease died with a progressive neuropathy. CARE was an effective regimen for refractory NHL in these patients.     

Update of results of autologous bone marrow transplantation in lymphoma

A substantial proportion of patients with Hodgkin’s disease and non-Hodgkin’s lymphoma will fail to achieve a complete remission with initial chemotherapy or will relapse after attaining a complete remission. The results of conventional salvage chemotherapy regimens for these patients have been disappointing. This has led to the use of highdose therapy regimens which can be administered with the use of hematopoietic rescue (bone marrow transplantation). The use of bone marrow transplantation for patients with relapsed and refractory lymphoma has increased rapidly. Data from the North American Autologous Bone Marrow Transplant Registry indicate that approximately 40 % of autologous bone marrow transplants are being performed for patients with lymphoma. Several large series of transplantation for Hodgkin’s disease and non-Hodgkin’s lymphoma have been published in the last two years^1-12. The results of these series vary widely due to differences in patient selection and pre-transplant prognostic factors. Differences in supportive care and preparative regimens prior to transplant may also account for the wide range of outcomes reported after transplantation. Although these differences make it impossible to compare results of one series with another, it is clear that a significant proportion of patients can achieve long term disease free survival following high dose therapy with marrow transplantation. It is also important, however, to note that this form of therapy can be associated with substantial morbidity and mortality. Transplant-related mortality exceeds 20 % in some series. However, greater experience, better patient selection, and advances in supportive care, such as hematopoietic growth factors, are allowing many institutions to perform transplantation with mortality rates under 5 %.     

A pilot study of cyclical chemotherapy with high-dose methotrexate and CHOP (MTX-CHOP) in poor-prognosis non-Hodgkin's lymphoma (NHL)

Summary In a pilot study of cyclical chemotherapy in patients with poor-prognosis non-Hodgkin's lymphoma (NHL), high-dose methotrexate (MTX) 1 g/m² with folinic acid rescue was given as initial treatment and then between cycles of a single-arm CHOP combination administered every 4 weeks. Of 21 patients with previously untreated or minimally treated grade 2 (high-grade) histology stage II/III/IV NHL, 13 (62%) achieved complete remission (CR); the CR rate for stage III/IV patients was 56%. Of all 25 patients with grade 2 stage II/III/IV NHL, including previously treated patients, 16 (64%) achieved CR. The median folow-up of patients who completed treatment is currently 22 months and only 1 relapse has been recorded in the CR group. Only five of 24 grade 2 patients given the initial test MTX failed to show any response, and eight patients achieved partial remission (PR) as a result of this single treatment. The response to MTX-CHOP in nine patients with grade 1 (low-grade) histology NHL was poor; only two achieved CR. These findings lend support to other data which indicate a useful role for MTX in the induction chemotherapy of advanced high-grade NHL, though the optimum dosage and drug sequence have yet to be determined.for the Yorkshire Lymphoma Group (YLG)     

High-dose chemotherapy with autologous peripheral blood stem cell support in children with malignant diseases

The advanced malignant diseases are rarely responsive to regular chemotherapy. High-dose chemotherapy supported by infusion of autologous peripheral blood stem cell (PBSC) has already shown to have significant activity in these diseases[1]. Nineteen children with advanced malignant diseases being hospitalized in our hospital received high-dose chemotherapy supported by autologous PBSC between June 1992 and February 2005. MATERIALS AND METHODS Patient Characteristics Nineteen childr…     

CHOP-Bleo plus interferon for stage IV low-grade lymphoma

BACKGROUND: Alpha interferon (IFN) is an effective single agent for patientswith low-grade lymphoma, but until 1982 had not been integratedwith standard chemotherapy for these patients. Since relapsefrom complete remission (CR) is the rule for patients with advancedstage low-grade lymphoma, a maintenance IFN schedule was exploredfor patients in CR. PATIENTS AND METHODS: From 1982–1987, 127 patients with stage IV low-grade lymphomawere treated with cyclophosphamide, doxorubicin, vincristine,prednisone, and bleomycin (CHOP-Bleo) for 9–18 mo. (median13 mo.), followed by interferon alfa-n-1 (Wellferon^®) maintenancetherapy for 24 mo. for CRs. RESULTS: The overall response rate for the entire treatment program was73% CR and 23% partial remission. The median follow up was 59months. At 5 years, survival was 74%, failure-free survival(FFS) 47%, and FFS of CRs 60%. Compared to a group of 96 patientswith similar pretreatment clinical features treated with CHOP-Bleofrom 1972–1982, this represents a significant improvementfor both overall FFS (p – 0.01) and FFS of CRs (P <0.01). Toxicity from the IFN maintenance was generally acceptable,but even at the modest dose employed in this trial (3 x 10⁶U/m² three times weekly), dose modification was required inmore than 30% of patients, usually because of fatigue. CONCLUSIONS: The integration of IFN and conventional chemotherapy is feasibleand effective. Maintenance IFN prolongs remission duration forpatients with stage IV low-grade lymphoma.     

An effective oral combination in advanced relapsed Hodgkin’s disease prednisolone,etoposide, chlorambucil and CCNU

Summary Many patients with advanced Hodgkin’s disease continue to need palliative therapy, but where there is no curative intent, patients and doctors may prefer oral treatment only. This paper describes the preliminary experience of such a schedule. A total of 15 patients with advanced relapsed Hodgkin’s disease were treated with an oral regimen, PECC (prednisolone at 40 mg daily for 7 days, etoposide at 200 mg/m² on days 1 – 3, chlorambucil at 20 mg/m² on days 1 – 4 and CCNU at 100 mg/m² on day 1 only), repeated every 4 – 6 weeks. 12 patients had been extensively pretreated. 11 patients had extranodal disease and 8 had B symptoms when treatment was started. Eight patients achieved a complete remission, with a median duration of 7+ months, and five achieved a partial remission; the overall response rate was 86%. Haematological toxicity was the major side effect. There were no treatment-related deaths. All patients tolerated treatment well and the oral route has particular advantages for those unwilling or unable to accept intravenous treatment.     

含美罗华联合方案治疗复发耐药B细胞性非霍奇金淋巴瘤

Objective： The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy, Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease free survival （DFS） and overall survival （OS） of naive patients, but its role in the second-line therapy for relapsed non-Hodgkin＇s Lymphoma （NHL） remains to be defined, This study aimed to evaluate the efficacy of rituximab-containing salvage regimens for relapsed or refractory NHL, and observe the toxicities. Methods： The clinical data of 54 patients, who were with relapsed or refractory NHL and treated in the Cancer Center of Sun Yat-sen University, were analyzed retrospectively, Of the 54 patients, 29 were man, 25 were women, with a median age of 52.5 years old （range 18 to 75）; 50 patients （92.6%） scored 0-1 for the ECOG performance status; for second-line international prognostic index （slPI）, 21 （38.9%） scored 0-1,30 （55.6%） scored 2 to 3, and 3 （5.6%） scored 4-5; 40 cases were diffuse large B-cell lymphoma （DLBCL）, accounting for 74.1% of all subtypes, Rituximab was administered intravenously at a dose of 375 mg/m^2 at the day before each chemotherapy cycle, The second or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16 and FND, Results： Of the 54 patients, 49 received retuximab-containing salvage regimens, The objective response rate of the 45 evaluable cases was 68,8%, with a complete remission （CR） rate of 37.7%; 3 patients achieved CR after radiotherapy following rituximab-based regimens and 3 achieved CR after autologous hematopoietic stem cell transplantation, The most frequent adverse events were leucopenia, nausea and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever and pruritus. The median follow-up time was 18 months （range 2-86 months）; 5 patients were lost, 24 were dead （23 died of lymphoma, and 1 died of severe hepatitis）, the other patients remained alive. The median survival time was 32 months （range 2-86 months, 95% confidential interval 16-48 months）. The 1-, 2- and 3-year OS rates were 70.6%, 53,6% and 41,5%, respectively, The median TTP was 6 months （range 0-52 months）, The median PFS was 10 months （range 0-47 months, 95% CI 0-26 months）, The 1- and 2-year PFS were 49,3% and 41,3%. Conclusion： Rituximab-containing salvage regimens are effective and well tolerated therapy for patients with relapsed or refractory B-cell NHL, even those were extensively treated.     

Clinical Observation of FMD Regimen:Fludarabine,Mitoxantrone, Dexamethasone, in Treatment of Non-Hodgkin''s Lymphoma

Objective  To evaluate the clinical effectivity and toxicity of the regimen FMD (fludarabine, mitoxantrone, dexamethasone) in patients with non-Hodgkin’s lymphoma. Methods  Thirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell lymphoma, received FMD. Treatment comprised: fludarabine 25∼30 mg/m² days 1∼3, mitoxantrone 8∼10 mg/m² day 1, and dexamethasone 20∼30 mg/m² days 1∼5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole, fluconazole, acyclovir and immunoglobulin. Results  Of the thirty-two patients treated, the complete response (CR) rate, partial response (PR) rate and overall response (OR) rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7% and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3∼4 neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3∼4 thrombocytopenia. At a median follow-up of 24 (5∼54) months, the 2-year overall-survival rate and progression-free survival rate were (87.5 ± 1.4)% and (83.3 ± 1.6)% respectively. The 2-year OS and PFS rates of the indolent group were (93.75 ± 6.25)% and (87.5 ± 8.54)%. Conclusion  FMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin’s lymphoma, especially in indolent B-cell lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.     

Long-term Remission of Primary Central Nervous System Lymphoma by Intensified Methotrexate Chemotherapy

High-dose (1–3.5g/m²) methotrexate (MTX) followed by whole-brain radiation therapy (WBRT) has consistently improved length of survival in primary central nervous system lymphoma (PCNSL), but the prognosis remains dismal. To optimize and enhance the dose intensity of MTX, we applied MTX at 8g/m² to 20 patients with PCNSL. In an effort to lower the risk of neurotoxic treatment sequelae, the WBRT dose was reduced to 30Gy in cases of complete remission after MTX therapy. Further, omission of WBRT and administration of stereotactic radiotherapy (SRT) were undertaken in 3 older patients. The overall response rate to the MTX therapy was 83%. The median progression free survival (PFS) was 54 months with a median overall survival (OS) of 57 months. Achieving a complete response after MTX therapy was significantly associated with a longer PFS. Late neurotoxicity was encountered in 4 (50%) of 8 patients who were aged 60 years or older and received WBRT, but in none of 12 patients who were aged less than 60 years or avoided WBRT. All older patients who underwent SRT sustained complete remission without a dementing disease. Intensifying the MTX dosage to 8g/m² appears more promising in comparison to results reported with MTX doses of 1–3.5g/m². In younger patients, the establishment of complete remission by intensified MTX therapy and subsequent WBRT with a relatively lower dose could promise durable tumor remission with an acceptable neurotoxicity. In older patients, WBRT should be avoided to sustain a meaningful survival, and SRT may provide a valid strategy in terms of enhancing local disease control without undue risk.     

The treatment of disseminated non-Hodgkin's lymphoma of unfavourable histology

Summary Forty-eight consecutive previously untreated adults with advanced non-Hodgkin's lymphoma (NHL) of unfavourable histological type were referred to the Department of Medical Oncology at St. Bartholomew's Hospital, London, between 1972 and 1977. They received adriamycin, vincristine, prednisolone and L-asparaginase (OPAL) initially, and those in whom complete remission was achieved proceeded to cranial irradiation and intrathecal methotrexate, followed by continuous oral maintenance chemotherapy comprising weekly methotrexate, cyclophosphamide, and daily 6-mercaptopurine for 3 years. Complete remission was achieved in 24 of the 48 (50%). The median duration of remission was 10 months, nine patients continuing without replase for between 3 and 7 years. The median survival was 9 months, 12 patients being alive and disease-free (three in second remission) after between 3^1/2 and 8^1/2 years.The prognosis was significantly better in patients with nodal stages II and III (disease) than in those with stage IV, for both response (P=<0.05) and survival (P=0.002). Patients in whom complete remission was achieved survived significantly longer than those in whom it was not, regardless of stage.These results confirm our preliminary observations with this treatment programme that a proportion of patients with stage II and III unfavourable histology NHL may be curable although the outlook for stage IV remains poor.     

Oral etoposide in patients with hematological malignancies

Tumor responses after daily oral administration of low-dose etoposide have been demonstrated in both hematological and solid tumors. The aim of the present phase II trial was to determine tumor response, and toxicity and to delineate the pharmacokinetics of oral low-dose etoposide in patients with hematological malignancies in a palliative treatment setting. Thirty-two patients with non-Hodgkin’s lymphoma (NHL), acute myeloblastic (AML) and lymphoblastic leukemia, multiple myeloma, and myelodysplastic syndrome (MDS) were included. Patients were given oral etoposide, 100 mg once daily for 14 d in a 21-d cycle. Serum etoposide concentrations were determined on d 1, 7, and 14 of every cycle before etoposide administration and, in addition, 1, 2, 3, 4, and 24 h after drug intake on d 1. The median age of patients was 68 yr (range: 50–89 yr). The median time from diagnosis to inclusion in the study was 21 mo (range: 0.5–144 mo) and most patients had advanced disease and were heavily pretreated. Eleven patients completed three or more cycles. Eight of 11 patients with acute leukemia and 1 of 2 with MDS received only 1 course because of toxicity (n=5) or progression (n=4). One patient with AML, a Jehovah’s Witness, was treated up-front and achieved a complete remission and two patients with low-grade NHL gained a complete and a partial remission, respectively. Twenty-one of 32 patients were evaluable for toxicity during the first cycle. In 67%, the white blood cell count nadir was <2.0 × 10⁹/L and in 38%<1.0 × 10⁹/L. Platelet count nadir was less than 25 × 10⁹/L in 24% of evaluable patients. During all cycles (n=79), eight patients developed febrile neutropenia, four of whom with a fatal outcome. The correlation between the area under the curve (AUC) of the free fraction of etoposide and leukopenia was statistically significant at a log analysis (n=12; p<0.05). There was also a statistically significant correlation between the AUC and the 24-h concentration (n=15; p<0.005) and between the concentrations at 24 h and d 7 (n=11; p<0.005) of the free fractions of etoposide. In conclusion, etoposide had a moderate clinical effect in this group of heavily pretreated patients. Moreover, toxicity was substantial, in particular leukopenia, which correlated to the free-etoposide AUC.     

Selective incorporation of111In-labeled PHOTOFRIN™ by glioma tissuein vivo

The use of PHOTOFRIN for photodynamic therapy of human gliomas has been studied by i.v. administration and laser photosensitization. Defining the uptake of PHOTOFRIN in the patient's tumor in comparison with the surrounding normal brain tissue is highly desirable for patient selection and study ofin vivo kinetics. We utilized a non-invasive approach to the detection of PHOTOFRIN uptake in brain tumors with¹¹¹In-oxine radiolabeled PHOTOFRIN and external imaging and quantitation using a gamma camera. Biodistribution of¹¹¹In-labeled PHOTOFRIN in 13 organs was determined in four dogs and 15 mice with gliomas.^99mTc-DTPA was used as a control for nonspecific uptake. The greatest concentration of¹¹¹In-PHOTOFRIN in the brain tumor occurred at 24 hours post i.v. administration. The brain tumor PHOTOFRIN uptake was seven times greater than that of normal brain. The decreased blood background at 72 hours made this the optimum time for imaging. Specific tumor tissue uptake of¹¹¹In-PHOTOFRIN occurred, well beyond that resulting from blood-brain-barrier (BBB) breakdown.     

Clinical characteristics and prognostic factors in Chinese patients with Hodgkin’s lymphoma

The aim of our study is to investigate the clinical characteristics and prognostic factors in Chinese Hodgkin’s lymphoma patients. It is known that clinical characteristics and epidemiology of Hodgkin’s lymphoma in China are different from Western countries. In total, 137 consecutive, previously untreated patients with Hodgkin’s lymphoma at Sun Yat-Sen University Cancer Center were enrolled. Among these patients, 92 were male and 45 were female, with a median age of 28 (range: 2–76) years. The bimodal age curve of classical Hodgkin’s lymphoma analyzed from our patients was not obvious as the Western population, showing an early peak in 25 years and a second peak in 45 years. Most of the patients (41.6%) were classified as nodular sclerosis classic Hodgkin’s lymphoma. Results showed that the 5-year overall survival, event-free survival, and disease-free survival rates were 97.7, 85.0, and 94.0%, respectively. Lymphopenia at diagnosis was related to poorer overall survival (P = 0.015) and event-free survival (P < 0.001) in all-stage Hodgkin’s lymphoma patients. Multivariate analysis showed that lymphopenia as an independent unfavorable prognostic factor influenced event-free survival (P = 0.015). The international prognostic score ≥ 5 was also the only independent prognostic factor of disease-free survival in advanced-stage patients (P = 0.046). Our findings demonstrated that some clinical characteristics of Hodgkin’s lymphoma in China were different from those in the Western countries. Lymphopenia was an effective prognostic predictor in both early stage and advanced stage.     

Increased LAK and T cell activation in responding renal cell carcinoma patients after low dose cyclophosphamide,IL-2 andα-IFN

Immunologic monitoring of cancer patients treated with IL-2 might help to determine functions of significance for the clinical outcome. Some immune functions in patients with advanced renal cell carcinoma were studied during treatment with low dose cyclophosphamide,α-interferon and IL-2. Cyclophosphamide (500 mg m⁻²) was given day 1, andα-interferon (3×10⁶ u i.m.) and continuous infusion of IL-2 (18×10⁶ u m⁻² day⁻¹) for days 4–9. The cycle interval was 3 weeks. Two to six cycles were given. Eleven patients entered the study. One patient achieved a partial remission, two patients had a minor response and four had a stable disease (‘responding patients’). NK cell activity (K562) increased in all patients while LAK cell activity (against a renal cell carcinoma cell line, A498) was significantly augmented only in responding patients. In the responder group, there was a significant increase in CD3⁺/HLA-DR⁺ T-cells. In parallel, there was a significant decrease in CD45RA⁺ cells as well as in the CD4/CD8 ratio. These data might indicate an expansion of activated T cells with a reduction of cells with a suppressor phenotype in responding patients. The results corroborate the importance of activation of LAK cells and T cells during IL-2 therapy of cancer patients.     

E-SHAP: An effective treatment in selected patients with relapsed non-Hodgkin's lymphoma

BACKGROUND:: The optimal treatment of relapsed or refractory non-Hodgkin'slymphoma is unknown. The reported encouraging results of a salvageregimen, E-SHAP (etoposide 40 mg/m²/day x 4, methyl prednisolone500 mg daily x 4, cytosine arabinoside 2 gm/m² one dose andcisplatinum 25 mg/m²/day x 4), at the MD. Anderson Hospitalin Texas, which resulted in a 65% response rate, could not bereproduced in the United Kingdom (0% response). PATIENTS AND METHODS:: Twenty-six patients with relapsed (n = 16) or refractory (n= 10) non-Hodgkin's lymphoma were treated at our Centre by amodified E-SHAP regimen (cytosine arabinoside 1 gm/m² one dose).The treatment was intended as remission induction before BMT(n = 16), as salvage by itself (n = 5) and for palliation ofsymptoms (n = 5). RESULTS:: The overall response rate was 72% (CR = 7 and PR = 11). A comparisonof Kaplan-Meier curves showed a statistically significant improvementin median relapse-free survival in patients who had previouslyachieved CR (p = 0.0012), no bulky disease (P = 0.0006) andno B-symptoms (P = 0.0004). The toxicity was acceptable: 8 instancesof febrile neutropenia, 2 of reversible renal impairment and2 symptomatic electrolyte abnormalities. No fatal toxicitieswere encountered. The median time to treatment failure was 191days and median overall survival was 190 days. CONCLUSIONS:: E-SHAP is an active combination chemotherapy when used as asalvage regimen or for remission induction before bone marrowtransplantation in selected patients with relapsed non-Hodgkin'slymphoma. Patients who previously achieved CR, with low tumourburden and no B-symptoms are the best candidates for this treatment.It has a limited palliative effect. non-Hodgkin's lymphoma, salvage chemotherapy, etoposide, cisplatinum