The modified Dunn procedure for slipped capital femoral epiphysis: the Bernese experience.

PURPOSE: Based on previous investigations on the vascular blood supply to the femoral head, a technique for anatomical reduction after slipped capital femoral epiphysis was developed. This technique is a modification of the original technique by Dunn using a retinacular soft-tissue flap. This allows the visual control of the epiphyseal vascular blood supply. We report the experience at the inventor's institution with a critical discussion of the available literature. METHODS: Using a trochanteric osteotomy for surgical dislocation of the hip, a retinacular soft tissue flap is created containing the deep branch of the medial femoral circumflex artery, the external rotators and the capsule. The femoral epiphysis can be mobilised safely and reduced on the femoral neck after resection of the almost constantly present reactive metaphyseal callus. RESULTS: In our institution, the rate of avascular necrosis with 2% is comparably low to Dunn's original results. It is only present in cases where no bleeding was already evident before reduction of the epiphysis. The ten-year long-term results are favorable in these cases with a good functional result and only little progression of osteoarthritis. However, other authors have reported higher rates of avascular necrosis up to 24% in their initial experience. CONCLUSIONS: In experienced hands using the correct meticulous surgical technique, the results are favorable regarding the rates of avascular necrosis, the functional outcome and the development of radiographic osteoarthritis - even in acute and severe cases. Avascular necrosis is rare but can be observed if there is no evidence of intra-operative femoral head perfusion before and after reduction of the epiphysis.

Randomized trial showing equivalent efficacy of filgrastim 5 micrograms/kg/d and 10 micrograms/kg/d following high-dose chemotherapy and autologous bone marrow transplantation in high-risk lymphomas.

PURPOSE: To evaluate the effect of two filgrastim dosages after autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Eighty-six patients were enrolled onto a multicenter, randomized, open-label study. The study compared the efficacy and safety of two different doses of filgrastim, 5-microgram/kg/d subcutaneous (SC) bolus injection and 10-microgram/kg/d SC continuous infusion, starting on day 1 following ABMT. RESULTS: Both patient groups were well matched in terms of demography and disease. The results showed no statistical difference in the median time to reach an absolute neutrophil count (ANC) of 0.5 x 10(9)/L (11 days; P = .685) and no difference in the median duration of neutropenia (10 v 11 days, respectively; P = .567) between either dose of filgrastim. The incidence and duration of fever and neutropenic fever were the same in both groups. The number and mean duration of clinically and documented infections, duration of intravenous (IV) antibiotics, time to discharge from hospital, and tumor response also were similar in both groups. CONCLUSION: This study demonstrates that a dose of filgrastim 5 micrograms/kg/d administered as a daily SC bolus injection has a similar efficacy and safety profile compared with the 10-microgram/kg/d dose administered as a SC continuous infusion. The lower dose of filgrastim has potential cost-saving implications in terms of both the dose of drug administered and the ease of administration. Based on these findings, the recommended dose of filgrastim after ABMT should be 5 micrograms/kg/d.

Randomized study of recombinant human granulocyte colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation for high-risk lymphoid malignancies.

PURPOSE: The aim of this prospective randomized trial was to examine the efficacy and safety of filgrastim after high-dose chemotherapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Patients with poor-risk non-Hodgkin's lymphoma or relapsed Hodgkin's disease were treated in a randomized, open-label trial to study the use of filgrastim as an adjunct to high-dose chemotherapy and ABMT. Of 43 assessable patients, 19 were randomized to receive filgrastim by continuous subcutaneous infusion at a dose of 10 micrograms/kg/d, 10 to filgrastim 20 micrograms/kg/d, and 14 to a parallel control group that received no filgrastim after ABMT. RESULTS: For all filgrastim-treated patients analyzed together, the median time to neutrophil recovery > or = 0.5 x 10(9)/L after the day of ABMT was significantly accelerated to 10 days compared with 18 days in control patients (P = .0001). The median number of platelet transfusions was identical in both groups. Clinical parameters, including the median number of days with fever (1 v 4, P = .0418) and neutropenic fever (5 v 13.5, P = .0001) were significantly shorter in the filgrastim than in the control group. The number of days on intravenous antibiotics and duration of hospitalization were also shorter in the treated groups; however, the differences did not reach statistical significance. For patients treated with the two different dose levels of filgrastim, the neutrophil recovery and clinical results were similar. Filgrastim-associated toxicity appeared to be minimal, with five adverse events considered at least possibly related to filgrastim: two in the higher-dose group and three in the lower-dose group. All of these were rated moderate, except one case of severe bone pain that did not preclude continued filgrastim treatment at a lower dose. Survival and relapse-free survival were similar for control and filgrastim-treated patients. CONCLUSION: Taken together, the results of this first randomized study support the role of filgrastim given as an adjunct to ABMT in accelerating neutrophil recovery, as well as in reducing treatment-related morbidity and overall duration of the treatment procedure.

Improved short- and long-term XTT-based colorimetric cellular cytotoxicity assay for melanoma and other tumor cells.

A tetrazolium compound, XTT, bioreducible to a water-soluble formazan was used to develop a simplified cellular cytotoxicity assay. Most (13/15 melanoma and 2/3 colon carcinoma cell lines tested metabolized XTT greater than 50 times more efficiently than the lymphoid effector cells, and thus the test could be performed without separation of the effector from the target cells. The XTT assay (XTT-A) was compared to the standard 51chromium-release assay (51CrA) in terms of sensitivity as well as intra- and interassay variability using low effector to target cell (E:T) ratios and both short and long incubation periods. The correlation coefficient (r) for percent specific lysis (%SL: 35.0 +/- 15.0 versus 30.2 +/- 15.8) or lytic units (LU20/10(7) effector cells: 405 +/- 208 versus 357 +/- 227) between XTT-A and 51CrA was 0.86 for 4 h XTT-A and 51CrA (n = 37). Due to a poor performance of the 51CrA after 24 h incubation of effector and target cells, the correlation coefficient for 24 h assays was reduced to 0.79 (n = 44,%SL = 63.3 +/- 23.9 versus 55.5 +/- 26.6, and LU = 1267 +/- 982 versus 1017 +/- 691). Inter- and intra-assay variability of XTT-A were significantly lower than those for 51CrA. The total background values for XTT-A and 51CrA were similar in 4 h cytotoxicity assay and lower for XTT-A in assays with 24 h incubation. The sensitivity, in terms of discrimination between effector cells with different lytic capacity and targets with different susceptibility, was identical. The XTT-A was simpler, cheaper, and safer to perform than the 51CrA. Furthermore, the XTT-A was suitable for long-term assays and allowed experiments without requiring trypsinization of tumor cells grown in 96-well plates prior to testing.

[Tumor screening with special reference to breast and prostate carcinoma]. / Tumorscreening unter besonderer Berücksichtigung von Mamma- und Prostatakarzinom.

After a theoretical introduction regarding screening with tumor markers and other examinations the current knowledge is discussed from the view points of an epidemiologist and a clinician as well. Screening for persons with normal risk is only advocated for cervical carcinoma and breast cancer in women aged 50 to 70 years. Screening for colon cancer with fecal occult blood tests remains unsatisfactory. Screening for prostate cancer is not recommended due to still lacking evidence of reduction in mortality and a high potential of side effects induced by early therapy with curative intent. Screening for ovarian cancer and lung cancer is not justifiable with current technology. However, persons with a known hereditary cancer syndrome or affected first-degree relatives have a much higher risk justifying screening for colon, prostate or breast cancer even below the age of 50 years.

[Overdose with melphalan (Alkeran): symptoms and treatment. A review]. / Uberdosierung von Melphalan (Alkeran): Symptome und Behandlung. Eine Ubersicht.

The symptomatology and outcome of three of our own cases with Melphalan overdose are presented. The literature regarding Melphalan overdose and its toxicity when given in normal and high doses is reviewed. Two of our cases with injection of less than 100 mg/m2 recovered from marrow aplasia within 3 weeks without major complications. The third patient died 6 days after injection of 290 mg/m2 Melphalan, probably due to cardiac arrhythmia before complete marrow failure had established. After intravenous application of more than 125 mg/m2 gastrointestinal side effects such as hemorrhagic diarrhea or even bowl perforation may be observed. These, together with a syndrome of inadequate ADH-secretion and electrolyte disturbances were the predominant clinical problems and the reasons for early death before infectious or bleeding complications due to prolonged marrow aplasia occur. Therapeutic measures are discussed. Due to the lack of a clinically useful antidote and detoxification method only symptomatic treatment is recommended. Colony stimulating factors such as GM-CSF G-CSF may improve the prognosis of moderate to severe Melphalan overdose.

Placebo controlled phase I/II study of subcutaneous GM-CSF in patients with germ cell tumors undergoing chemotherapy.

Patients with metastatic germ cell tumors undergoing five-day chemotherapy with etoposide, vinblastin, bleomycin and cisplatinum were given recombinant GM-CSF (mammalian glycosylated, Sandoz/Schering-Plough) at increasing dose levels of 75, 150, 300 or 600 micrograms protein/day in a double blind placebo controlled study. The drug was administered SC twice a day for 5 days starting 24 hours after completion of chemotherapy. Fourteen treatment courses, 10 with GM-CSF and 4 with placebo in 11 patients were evaluable for assessment of toxicity and hematological recovery, and 2 were not evaluable due to complications of progressive germ cell tumor. One patient receiving the highest dose level developed a delayed skin reaction at the site of injection. Fever under 38.5 degrees C and a flu-like syndrome were observed in 4/5 patients receiving the higher two dose levels, but not with lower dose levels or placebo. Two patients experienced mild bone pain. The neutrophil nadir was similar in the two groups, but the duration of neutropenia was significantly shorter in the GM-CSF group. At day 21 of chemotherapy the neutrophil count was 2.57 +/- 1.37 10(9)/l with GM-CSF, and 1.01 +/- 0.56 10(9)/l with placebo (p less than 0.05). Patients receiving GM-CSF could be retreated on day 21, whereas in patients given placebo, retreatment was delayed for an average of 7 days (p less than 0.05). Thus, a 5-day treatment with GM-CSF given subcutaneously resulted in a significant shortening of neutropenia and allowed for the timely administration of the subsequent cycle of chemotherapy.

[High-dose chemotherapy with autologous bone marrow transplantation: 11 years' experience in Zurich]. / Hochdosis-Chemotherapie mit autologer Stammzelltransplantation: 11 Jahre Zürcher Erfahrung.

High-dose chemotherapy with autologous bone marrow or peripheral blood stem cell transplantation has gained widespread acceptance for the treatment of certain malignancies. Since the introduction of this therapy in 1988 we have treated 272 patients. Indications for high-dose chemotherapy were high-risk large cell lymphoma and lymphoblastic or Burkitt lymphoma in first remission (73 patients), non-Hodgkin's lymphoma in chemosensitive relapse (65 patients), Hodgkin's lymphoma in relapse (52 patients), germ cell tumours with inadequate response to chemotherapy (34 patients), multiple myeloma (29 patients), and other malignancies (19 patients). Treatment mortality was 1.8%. The 3-year event-free survival and overall survival for all patients were 48 and 61% respectively. High-dose chemotherapy with autologous stem cell transplantation has become a safe procedure and is considered the treatment of choice for relapsed large cell lymphoma, relapsed Hodgkin's disease, stage II or III multiple myeloma, and germ cell tumours with inadequate response to cisplatin-based chemotherapy. In other situations, including aggressive lymphoma with risk factors, acute leucaemia or breast cancer, the superiority of high-dose over conventional chemotherapy remains to be proven. Patients with such diseases should not receive high-dose chemotherapy outside a controlled clinical study.

[Immunotherapy of tumors using interleukin-2 and lymphokine-activated killer cells]. / Immuntherapie von Tumoren mit Interleukin-2 und Lymphokin-aktivierten Killer-Zellen.

The tolerance and effectiveness of an interleukin-2 analog (rIL-2) in combination with lymphokine activated killer (LAK) cells has been studied. 14 patients with metastatic solid tumors, including 8 renal cell carcinomas, 3 melanomas and 3 extragonadal germ cell tumors refractory to standard therapy, were treated for a 3-week period. rIL-2 was administered as a bolus at 30,000 U/kg every 8 hours on days 1-5 and days 12-19. Leukapheresis was done on days 8-12, and lymphocytes were incubated with rIL-2 for 3-4 days in vitro and reinfused on days 12, 13, and 15. rIL-2 dose and schedule were adjusted according to toxicity. The major side effects were constitutional symptoms and a capillary leak syndrome with hypotension and impaired renal function. Partial responses were documented in 2/8 renal cell carcinomas and 1/3 melanomas. The response durations were 1, 5 and 6 months.

Thyroiditis after treatment with interleukin-2 and interferon alpha-2a.

Serial thyroid functions studies were carried out in patients with melanoma and renal cell carcinoma treated with interleukin-2 (3 MU m-2 by continuous infusion days 1-4) and interferon alpha-2a (6 MU m-2 subcutaneously on days 1 and 4), both given on alternate weeks. The results on eight patients who completed at least three cycles of treatment are described. Four patients developed thyroid dysfunction with a hyperthyroid phase of 2 weeks followed by a hypothyroid phase ranging from 12 to 24 weeks. Two patients became clinically symptomatic and required treatment. Fine-needle aspirates of the thyroid were obtained in three patients with thyroid dysfunction. The cytology revealed a mixed cellular infiltrate with lymphocytes and histiocytes, and immunocytochemical staining showed strong HLA-DR expression of all thyrocytes, both suggestive of an autoimmune thyroiditis. One patient with thyroiditis developed anti-thyroglobulin antibodies, the serology of all other patients was normal. Patients with thyroid dysfunction tended to have higher in vivo stimulated lytic activity of peripheral mononuclear blood cells and had significantly higher levels of CD16 positive blood cells as compared to euthyroid patients. The possibility of autoimmune thyroiditis should be anticipated in future trails combining interleukin-2 and interferon alpha-2a.

Clinical and immune modulatory effects of alternative weekly interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma.

The clinical and immune modulatory effects of interleukin-2 (IL-2) and interferon (INF) alfa-2a were examined in a phase II study in patients with metastatic renal cell carcinoma (six patients) and melanoma (eight patients). Treatment consisted in IL-2 3 MU/m2 continuous infusion days 1-4 and INF alfa-2a 6 MU/m2 subcutaneously day 1 and 4, both given on alternate weeks. Tumour response was assessed after four cycles of treatment or earlier, if necessary. Patients with stable disease or response were to be continued for another nine cycles or up to disease progression. The 14 patients received a total of 60 cycles of treatment. Major toxicities (WHO Grade III/IV) were fever, capillary leak syndrome with hypotension, nausea and vomiting, erythema with pruritus, leuco- and thrombopenia and sepsis with staphylococcus aureus. Five of 14 patients (36%) developed a self limiting autoimmune thyroiditis with HLA-DR expression on thyrocytes. Long term treatment toxicity was moderate with an average weight loss of 5% and an average fall in Karnofsky index of 10% compared to baseline. No responses were seen in renal cell carcinoma, two patients with melanoma had a partial and two a minor response with a duration of 1-7 months. Serial measurements of immune modulatory parameters showed a functional response to treatment with an increase of NK- and LAK-activity during the first two cycles, followed by a plateau and decrease during the third and fourth cycles. These findings were paralleled by a successive decline in treatment induced INF gamma response. These findings suggest, that alternative weekly treatment with IL-2 and INF alfa-2a results in an exhaustion of lytic capacity of NK- and LAK-cells and an attenuation of secondary cytokine release.

Index of pretreatment intensity predicts outcome of high-dose chemotherapy and autologous progenitor cell transplantation in chemosensitive relapse of Hodgkin's disease.

PURPOSE: To identify prognostic factors in patients with chemosensitive relapsed Hodgkin's disease treated by high-dose chemotherapy with autologous progenitor cell transplantation (HDC) and to compare the duration of treatment-free remission prior to HDC with the progression-free survival after HDC in individual patients. PATIENTS AND METHODS: Forty-five consecutive patients were analyzed retrospectively. We devised an index of pretreatment intensity (IPTI) based number of different chemo- and radiotherapy regimens given between diagnosis and HDC and on the duration of disease. RESULTS: With a median follow-up of 47 months the post-transplant event-free survival (EFS) was 44% and the overall survival (OAS) was 62% at four years. The IPTI allowed to discriminate between a low and a high-risk group with a four-year post-transplant EFS of 66% and 11% and a OAS of 87% and 28%, respectively (P = 0.0001). Of the 39 patients with sufficient follow-up after HDC, post-transplant EFS lasted on average > or = 18.5 months longer than the pretransplant treatment-free remission. CONCLUSIONS: HDC with the CBV regimen confers significant benefit to patients with chemosensitive relapsed Hodgkin's disease. The IPTI may help to select patients with a good response to HDC and to identify poor prognosis patients suitable for experimental protocols or palliative care only.

Fate of contaminating t(14; 18)+ lymphoma cells during ex vivo expansion of CD34-selected hematopoietic progenitor cells.

The use of ex vivo expanded CD34-selected hematopoietic progenitor cells (HPCs) for autologous stem cell support or gene therapy is a major area of research and is likely to increase in the future. At present, little is known about the fate of contaminating malignant cells during ex vivo expansion of CD34-selected HPCs. We established a competitive polymerase chain reaction (PCR) titration assay to determine the number of residual lymphoma cells before and after selection and ex vivo expansion of CD34-selected HPCs in patients with t(14; 18) translocation carrying non-Hodgkin's lymphoma. Seven bone marrow (BM) and 2 mobilized peripheral blood progenitor cell samples from 8 patients without histologic BM involvement at the time of the harvest were analyzed by competitive PCR titration assay and determined to contain between < or = 10 and 4,000 lymphoma cells/ 10(6) mononuclear cells (MNCs). Immunoadsorption enriched CD34+ cells from a mean of 5% (range, 1% to 9%) to a mean of 88% (range, 76% to 94%) of MNCs and resulted in a 1 to 4 log depletion of contaminating tumor cells. Two HPC samples became PCR negative after CD34 selection, whereas 7 samples still contained < or = 10 to 200 residual lymphoma cells/10(5) MNCs. CD34-selected cells were consecutively expanded in suspension culture in the presence of stem cell factor, interleukin-1 beta (IL-1 beta), IL-3, and IL-6. The mean increase of cells was 13-fold (range, 4- to 22-fold) at day 7 and 65-fold (range, 43- to 110-fold) at day 14 of culture. Expansion resulted predominantly in myelomonocytic differentiation, whereas B-cell antigen-expressing cells became undetectable. Six of the seven PCR-positive CD34-selected samples became PCR-negative for the t(14; 18) translocation at day 7 and/or 14 of expansion. One PCR-positive and one PCR-negative CD34-selected sample were PCR-positive after ex vivo expansion, but the number of residual lymphoma cells remained at the limit of detection. We conclude that CD34-selection does not eliminate contaminating lymphoma cells in the majority of t(14; 18)+ HPC harvests. However, during ex vivo expansion of CD34-selected HPCs, residual t(14; 18)+ lymphoma cells do not proliferate and become undetectable by PCR in the majority of cases.

Risk-adapted chemotherapy of germ cell tumors with carboplatin, etoposide and bleomycin for low-risk and cisplatin, etoposide and ifosfamide for high-risk patients. A single-center study.

The prognosis of germ cell tumors treated with chemotherapy depends on the presence of nonseminomatous tumor, clinical parameters based on the tumor volume and site, as well as on the level of the tumor markers AFP, betaHCG and LDH. We report here on the results of a risk-adapted approach to the chemotherapy of germ cell tumors. Patients with low-risk tumors, defined as seminomatous disease and/or nonseminomatous disease with a tumor mass <10 cm, less than 20 lung metastases, no liver, bone, or CNS metastases, and levels of AFP <1,000 IU/ml and betaHCG <10,000 IU/l, were to receive 4 cycles of carboplatin 400 mg/m(2) i.v. day 1, etoposide 120 mg/m(2) i.v. days 1-3 and bleomycin 30 IU i.v. days 1, 8 and 15 during the first 3 cycles (CEB(90)). Patients with high-risk disease were to receive 4 cycles of ifosfamide 1,500 mg/m(2) continuous infusion on days 1-4 together with mesna 1,200 mg/m(2) days 1-5, cisplatin 20 mg/m(2) i.v. days 1-5 and etoposide 100 mg/m(2) i.v. days 1-5 (VIP). Of the 60 patients treated with this risk-adapted approach, 51 had low-risk and 9 had high-risk disease. Forty-five of 51 patiens treated with CEB(90) achieved complete remission (CR), 4 achieved partial remission with marker negativity. Four patients with CR relapsed between 4 to 8 months after the start of chemotherapy. Of the 6 patients failing CEB(90), 3 were treated successfully with surgery or further chemotherapy. With a median follow-up of 52 months, the estimated cause-specific 3-year survival is 93% (95% confidence interval, CI, 80-98%). Seven of 9 high-risk patients treated with VIP achieved a CR and 1 patient relapsed. All 3 patients failing VIP had successful salvage therapy. With a medium follow-up of 63 months all patients remain alive and free of disease. Forty-six patients receiving CEB(90) were retrospectively classified to be in the good prognosis group according to the international germ cell consensus classification. Their estimated 3-year survival was 95% (CI 81-99%). We thus confirm that CEB(90) is a well-tolerated outpatient regimen with good results in good prognosis germ cell tumors. Bleomycin at a cumulative dose of 270 U might contribute substantially to the inferior effect of carboplatin as compared to cisplatin. However, in view of the results of randomized studies favoring cisplatin over carboplatin, it is not recommended to use this regimen outside a clinical trial.

Selection and immunomagnetic purging of peripheral blood CD34+ cells for autologous transplantation in B-cell non-Hodgkin's lymphomas.

BACKGROUND: Clonogenic tumor cells in the hematopoietic progenitor cell harvest may contribute to relapse after high dose therapy for B-cell malignancies. Purging of the HPC harvest requires large amounts of anti-B-cell antibodies, whereas CD34-selection enriches self renewing HPC's but malignant cells are still detectable in many CD34+ fractions. PATIENTS AND METHODS: We examined the feasibility and safety of a CD34-selection followed by purging with anti B-cell antibodies in 11 patients with B-cell non-Hodgkin's lymphomas undergoing high-dose therapy with cyclophosphamide, BCNU and etoposide with retransfusion of autologous HPC's. RESULTS: A mean number of 340 x 10(8) mononuclear cells was used for CD34-selection and immunomagnetic purging. CD34+ cells were enriched from a mean of 1.7% (range 0.2%-4.5%) to a mean of 68% (range 49%-87%) with a mean recovery of 27% (range 15%-43%). The mean number of retransfused CD34+ cells was 1.2 x 10(6)/kg (range 0.6-2.2 x 10(6)/kg) body weight with a median of 11 days (range 10-13 days) to neutrophil recovery of 0.5 x 10(9)/l and 17 days (range 13-25 days) to platelet recovery of 50 x 10(9)/l. Mean number of intravenous antibodies and inpatient days were 8 (range 0-14) and 22 (range 19-26) respectively. Major toxicity consisted in four septicemias. CONCLUSIONS: CD34-selected and purged HPC's are safe and mediate rapid hematological recovery after high dose therapy for B-cell non-Hodgkin's lymphomas.

[High-dosage chemo-radiotherapy with autologous bone marrow transfusion in malignant lymphoma: indications and personal experience]. / Hochdosierte Chemoradiotherapie mit Retransfusion autologen Knochenmarks bei malignen Lymphomen: Indikationen und eigene Erfahrungen.

We report the results of a pilot study of dose intensification with autologous bone marrow support in patients with malignant lymphoma. Since January 1988 11 patients with malignant lymphoma have been treated by intensive chemoradiotherapy or combination chemotherapy followed by autologous bone marrow support. 6 of the patients had non-Hodgkin's lymphoma in first remission with unfavorable histology and/or unfavorable clinical prognostic factors, and 5 patients were in second or subsequent remission (2 non-Hodgkin's lymphoma, 3 Hodgkin's disease). Bone marrow harvest and cryopreservation of marrow cells were uneventful. 10 patients showed full hematologic recovery, while one patient with Hodgkin's disease died early of pneumocystis pneumonia. With the exception of one interstitial pneumonitis of unknown etiology, the clinical course during hospitalization was otherwise uncomplicated. The mean duration of hospital stay was 33 days. 2 patients relapsed after dose intensification, while the others are in continued remission (median 7 months, range 2-14 months).

Short-term weekly chemotherapy followed by high-dose therapy with autologous bone marrow transplantation for lymphoblastic and Burkitt's lymphomas in adult patients.

BACKGROUND: Type and duration of treatment for highly aggressive non-Hodgkin's lymphoma has been a matter of debate over the past decade. To determine the therapeutic efficacy of an abbreviated treatment regimen, 26 patients with newly-diagnosed highly aggressive lymphomas, 17 of them belonging to the International Working Formulation (IWF) group I and 9 with Burkitt's lymphoma (IWF J), were entered in a study using short-term weekly chemotherapy followed by high-dose therapy and autologous bone marrow transplantation. PATIENTS AND METHODS: Besides histology, requirements for entry into to the study were age between 16 and 60 years, stage 1 bulky disease and elevated LDH or stage II to IV disease with or without bulk or elevated LDH, and an absence of HIV infection or CNS involvement at diagnosis. The treatment plan was 12 weeks of MACOP-B or VACOP-B chemotherapy followed by high dose therapy and autologous bone marrow transplantation in first complete remission. RESULTS: Twenty patients (76%), 16 (62%) of those on MACOP-B or VACOP-B, 1 who had received 2 cycles of ProMACE-CytaBOM prior to MACOP-B and 3 after a first salvage regimen, achieved complete remissions. Seventeen patients (65%) were transplanted in first remission, and 15 (58%) after induction treatment with only MACOP-B or VACOP-B. Reasons for not being given high dose therapy and autologous bone marrow transplantation (ABMT) were failure to achieve complete remission in 6 patients, early relapse in 2 and severe pulmonary toxicity associated with chemotherapy in 1. The median time of follow-up was 45 months. At 3 years, the estimated event-free survival was 31% (CI 14%-50%) and the overall survival 48% (CI 25%-67%). There were no deaths from toxic effects of treatment. Pretreatment factors associated with relapse were stage III or IV disease, age over 30 years and bone marrow involvement. Logrank analysis showed that age was the only factor significantly associated with poor event-free survival. CONCLUSION: Short-term weekly chemotherapy followed by high-dose therapy with the CBV regimen in first remission is not a higly effective treatment for advanced lymphoblastic and Burkitt's lymphomas. The 30% rate of failure to achieve partial remission after 6 weeks and/or complete response after 12 weeks of MACOP-B or VACOP-B treatment, as well as the 42% failure rate to undergo ABMT in first remission, suggest that more aggressive chemotherapy should be used in the beginning.

Tolerance and effectiveness of recombinant interleukin-2 (r-met Hu IL-2 [ala-125]) and lymphokine-activated killer cells in patients with metastatic solid tumors.

The tolerance of a recombinant human interleukin-2 (rIL-2, r-met Hu IL-2 [ala-125], Ortho Pharmaceutical) and its antitumor effectiveness in combination with lymphokineactivated killer (LAK) cells was examined in 26 patients with metastatic solid tumors, including 14 renal cell carcinomas, seven melanomas, three extragonadal germ cell tumors refractory to chemotherapy and two colon carcinomas. rIL-2 was administered as a bolus at 30,000 U/kg every 8 h on days 1-5 and days 12-19. Leukapheresis was done on days 8-12, lymphocytes were incubated with rIL-2 for 3 or 4 days in vitro and reinfused on days 12, 13 and 15. The mean number of reinfused cells was 5.1 x 10(10) per patient. IL-2 dose and schedule were adjusted according to toxicity. Patients received a median of 100% (range 87-100%) of planned rIL-2 on days 1-5 and a median of 71% (range 13-100%) on days 12-19. Capillary leak syndrome with hypotension and impaired renal function and CNS toxicity were the major reasons for dose modification. Patients with renal cell carcinoma, most of whom underwent a prior nephrectomy, had a reduced tolerance to rIL-2. Partial responses were documented in three renal cell carcinomas and one melanoma. The median response duration was 5.5 (range 1-6) months.