European Group for Blood and Marrow Transplantation (EBMT) registry data indicate that patients with relapsed HD given high-dose therapy (HDT), supported with PBPC might have a poorer outcome ...compared with those given BM. Since this can be due to the infusion of contaminating tumor cells in the PBPC products, we studied the presence of minimal residual disease and tested whether CD34+ cell enrichment was able to remove atypical CD30+ cells from PBPC grafts.
Eighteen HD patients eligible for HDT were included in the study. By the use of immunocytochemistry (ICC), mononuclear cells from BM and peripheral blood (PB) before mobilization, PBPC products and selected CD341 fractions were stained using anti-CD30 MAb (Ber-H2) and the APAAP (alkaline phosphatase-anti-alkaline phosphatase) method. Cells scored as atypical CD30+ cells were large- to medium-sized, with membranous, cytoplasmatic and/or Golgi positivity for CD30.
Nine out of 11 BM tested were positive, while 14 of 14 PB and 18 of 18 PBPC contained atypical CD30+ cells. The total number of atypical CD301 cells was significantly higher in PBPC than in the corresponding BM. CD341 cell enrichment employing ISOLEX 300I gave a purity and yield of 99.2% (range 97.8–99.7) and 49.6% (range 30.0–78.4), respectively. After HDT a median of 5.8 3 106 (range 2.7–20) CD34+ cells/kg was infused. Neutrophil counts of . 0.5×109/L and platelet counts of . 20×109/L were achieved at Day 12 (range 10–17) and at Day 10 (range 7–15), respectively. Sixteen of 18 CD34+ selected products had no detectable atypical CD30+ cells, while two had a low number. After HDT, the overall survival was 80% and the event-free survival was 69%, with a median follow-up of 24 months (range 1–36).
We show that contaminating atypical CD301 cells in PBPC can efficiently be removed by CD34+ cell enrichment, and the use of such grafts following HDT gives fast and sustained engraftment.
To evaluate health-related quality of life (HRQOL) in adults treated with high-dose chemotherapy followed by allogeneic (SCT) and autologous (ASCT) stem-cell transplantation 1 year after ...transplantation, using data from concurrent lymphoma patients receiving combination chemotherapy (CT) as a reference.
Forty-one leukemia patients (SCT group), 51 lymphoma patients (ASCT group), and 85 CT patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire at baseline and after 1 year.
The SCT group (median age, 36 years) had better functioning scores and less symptomatology at baseline compared with the ASCT (median age, 41 years) and CT (median age, 37 years) groups. Statistically significant differences of 10 or more points on the 0 to 100 scales were found for 10 of 15 scales and items (P< or =.01) between the SCT and ASCT groups. Global quality of life (79 v 58, P<.0001), role function (83 v 65, P = .001), sleep disturbances (6 v 28, P<.0001), and fatigue (25 v 44, P = .0001) deviated most. The differences were 10 or more points for seven of 15 scales and items comparing the SCT and CT groups, with sleep disturbances (6 v 35, P<.0001) and pain (11 v 29, P<.01) deviating most. Differences across groups were smaller after 1 year; cognitive function was the only scale with a statistically significant difference (ASCT 80 v CT 89; P = .002). Patterns of change in HRQOL scores were different between groups during follow-up. A great improvement was found in the ASCT group (P<.01 for emotional and role function, fatigue, appetite, and constipation), whereas no significant changes were observed for the SCT group.
Prospective studies with extended follow-up periods are necessary to separate a slow recovery process from more permanently reduced HRQOL after transplantation and to examine the late side effects from previous treatment.
In search for subgroups of diffuse large B-cell lymphoma (DLBCL) with different histogenetic origin and prognosis, as has been described by gene expression profiling, we examined tumor specimens from ...125 patients with DLBCL, uniformly treated by either cyclophosphamideAdriamycin-vincristine-prednisone or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin in a multicenter trial set by the Nordic Lymphoma Group 1989-1994.
Bcl-6, CD10, and CD40 were chosen as markers for a germinal center phenotype, CD23 as a marker of pre/early germinal center origin, and CD138 as a marker for postgerminal center origin. In addition, expression of the apoptotic regulators bcl-2 and bax was analyzed. Immunohistochemical analysis was performed using the EnVision method.
CD10 was positive in 51%, bcl-6 in 97%, and CD138 only in 2% of the cases. No prognostic conclusions could be drawn from analysis of these factors. CD40 was positive in 76% of the cases. This group was associated with superior time to treatment failure (P = 0.027) and overall survival (OS; P = 0.0068). By Cox regression analysis, positivity for CD40 was shown to be a prognostic factor for OS, independent of International Prognostic Index. CD23 was positive in 16% of the cases (all CD5 negative and all CD40 positive). This group showed a strong tendency for better OS (P = 0.033). CD40 expression correlated with bax but not with bcl-2 expression.
CD23 and CD40 expression seems to be prognostically favorable in DLBCL. This may be secondary to a germinal center origin or attributable to increased apoptosis via induction of bax and/or enhanced T-cell interaction, resulting in improved autologous tumor response. Confirmatory studies are necessary.
High-dose therapy with autologous blood progenitor cell support is now routinely used for patients with certain malignant lymphomas and multiple myeloma. We performed a prospective cost analysis of ...the mobilization, harvesting and cryopreservation phases and the high-dose therapy with stem cell reinfusion and hospitalization phases. In total, 40 consecutive patients were studied at four different university hospitals between 1999 and 2001. Data on direct costs were obtained on a daily basis. Data on indirect costs were allocated to the specific patient based on estimates of relevant department costs (ie the service department's costs), and by means of predefined allocation keys. All cost data were calculated at 2001 prices. The mean total costs for the two phases were US$ 32,160 (range US$ 19,092-50,550). The mean total length of hospital stay for two phases was 31 days (range 27-37). A large part of the actual cost in the harvest phase was attributed to stem cell mobilization, including growth factors, harvesting and cryopreservation. In the high-dose chemotherapy phase, the most significant part of the costs was nursing staff. Average total costs were considerably higher than actual DRG-based reimbursement from the government, indicating that the treatment of these patients was heavily subsidized by the basic hospital grants.
Stage I High-Grade Non-Hodgkin's Lymphoma Knut Lote, Harald Holte, Ole Nome, Ruth Langholm, Stein Kvaløy
Acta oncologica,
2000, Letnik:
39, Številka:
7
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
We report long-term survival and prognostic factors in 252 patients with stage I high-grade lymphoma. Median patient age was 64 years and 49% of patients had extranodal lymphoma. Premenopausal women ...had less risk of extranodal lymphoma than older women or males (p < 0.002). Disease specific 5 and 15 years' survival in patients > 64 years was 83% and 76%, respectively; compared to 54% and 46% in patients > 64 years of age. Age, non-centroblastic histology, B-symptoms, and increased serum lactate dehydrogenase (LDH) were independently negative prognostic factors (p < 0.01), while extranodal, testicular, or bulky (> 6 cm) lymphoma presentation were of no prognostic significance. A radiation dose of 40 Gy in 2 Gy fractions to the primary site prevented in-field relapse in 159 of 173 irradiated patients (92%) and only three of 173 patients (1.7%) had local relapse in the absence of systemic dissemination.
A total of 221 consecutive early stage Hodgkin's disease (HD) patients were given mantle field irradiation only or in combination with chemotherapy in 1971-1991. In 1994 these patients responded to a ...mailed self-report questionnaire covering items on late medical symptoms. Of 200 patients (91%) who reported that their thyroid function had been tested, 110 patients (55% of those tested) had thyroid hypofunction at follow-up in 1994. Ninety-five patients (86% of patients with biochemical hypothyreosis) had started hormonal substitution. In 1993 and 1994, 101 of these patients who had received mantle field irradiation in 1980-1988 were called in for interview, clinical examination and thyroid function tests. Eighteen patients (18%) had started hormonal substitution treatment earlier, but 58 (70%) of the other 83 patients were found to have biochemical hypothyreosis. Of the 221 patients who completed the questionnaire, 66 patients (30%) reported dyspnoea on exertion for more than 3 years after treatment, 8 patients (4%) reported a history of myocardial infarction, 6 patients (3%) reported pericardial disease and 25 patients (11%) heart valve disease. Increased expenses incurred for dental care were reported by 106 patients (48%), increasing to 55% when Waldeyer's ring had been irradiated. The consequences of late sequelae after mantle field irradiation for future treatment are discussed.
The long-term survival of patients with advanced stage aggressive lymphoma has not improved significantly during the last twenty years. In a randomised trial, the efficacy of MACOP-B, a six-drug ...weekly chemotherapy regimen, was compared to CHOP, the current standard regimen, in terms of overall and failure-free survival, toxicity and health related quality of life.
Four hundred five patients with aggressive lymphoma, stage II-IV, age 18-67, were randomised to receive either 12 weeks of MACOP-B or 8 courses of CHOP over 24 weeks. Special emphasis was put in the definition of Ann Arbor stage in extranodal disease. A subset of 95 patients also entered a quality of life study, based on the EORTC QLQ-C30.
Thirty-one patients were ineligible. Among the remaining 374 patients, the median age was 52 years. According to the age-adjusted International Prognostic Index, 37% were 'high-intermediate' or 'high-risk' patients. No difference could be demonstrated, either in overall survival (60% at five years in the MACOP-B group and 59% in the CHOP group) or in failure-free survival (47% at five years with MACOP-B and 44% with CHOP). In terms of quality of life, physical function and global quality of life were more impaired in patients receiving MACOP-B, who also exhibited more non-haematological toxicity.
No superiority of MACOP-B compared to CHOP could be demonstrated. CHOP remains the treatment of choice in low-risk patients. At present, intensified or experimental treatment should be reserved for high-risk disease.
To study lumbar bone marrow by means of MR imaging before and after bone-marrow transplantation in lymphoma patients. Particular emphasis was paid to heterogeneity and to focal manifestations, i.e. ...appearances that could simulate tumor.
Twenty-two patients who were disease-free for a minimum of 30 months after transplantation were studied in 107 MR examinations. Two radiologists visually evaluated coronal T1-weighted and short inversion time inversion-recovery (STIR) images.
T1-weighted images demonstrated a more heterogeneous marrow after transplantation than before it. Sharply defined focal low signal intensity areas appeared on this sequence in 5 (23%) of the 22 patients at between 21 and 60 weeks after transplantation. The mean age of these 5 patients was 48.4 years (range 42-54 years). The difference in age between these 5 patients and the remaining 17 patients, who had a mean age of 33.4 years (range 14-51 years), was statistically significant (p < 0.01, Student's t-test, 2-sided test).
Sharply defined focal low signal intensity areas may be seen on T1-weighted images of bone marrow in patients who are in complete remission after transplantation, particularly in those aged over 40-45 years.
The aim of the present study was to investigate whether the early changes in the immune system observed after ABMT would persist over years. Eighty-five patients with malignant lymphoma were treated ...with ABMT in Norway from 1987 until 1993. Of the 46 patients in CR by 1997, 36 were enrolled in our study. Median time from ABMT was 5 years (4-10 years). Immunophenotyping showed an increase in the median number of B cells (0.35 x 109/l in patients vs 0.28 x 109/l in controls), and a decrease in T cells (1.08 vs 1.35 x 109/l). Furthermore, a lower median count of CD4+ T cells (0.54 x 109/l in patients vs0.87 x 109/l in controls) resulted in reduced CD4/CD8 ratios (0.8 in patients vs 1.6 in controls). The subgroup of CD4+ T cells expressing the 'naive' phenotype CD45RA was 19.5% in patients vs 38% in controls. In contrast, the fraction expressing the 'memory' phenotype CD45RO was higher in the ABMT group (76% vs 54%). When stimulated, larger fractions of CD3+CD4+ cells in patients produced IFN-gamma (32% vs 16%) or IL-4 (7% vs 1%) compared to controls; thus a differentiation into the functionally separate subgroups Th1 and Th2, with a dominant Th2 response. Our data further suggest that the decrease in CD4+ T cell counts and the imbalance between CD45RA+ and CD45RO+ subsets persists 4-10 years after ABMT.
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