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author:("delfin, C")
1.  Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study 
British Journal of Cancer  2000;82(7):1254-1260.
We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57–2.42;P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months;P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients. © 2000 Cancer Research Campaign
doi:10.1054/bjoc.1999.1087
PMCID: PMC2374495  PMID: 10755397
multiple myeloma; stage I; early or delayed treatment; survival
2.  Relevance of age on survival of 341 patients with multiple myeloma treated with conventional chemotherapy: updated results of the MM87 prospective randomized protocol. Cooperative Group of Study and Treatment of Multiple Myeloma. 
British Journal of Cancer  1998;77(3):485-491.
Age could influence the prognosis of multiple myeloma patients treated with conventional chemotherapy. Between January 1987 and March 1990, 341 consecutive previously untreated patients with multiple myeloma received chemotherapy within the prospective, multicentre, randomized Protocol MM87. Survival was evaluated in patients aged > or < or = 66 years (the median age for the whole series) and in a subgroup of patients aged < 55 years. These groups were similar for main clinical characteristics, including results of cytostatic treatment. As of May 1996, 271 (79%) of the 341 patients had died, and median follow-up of the 70 (21%) living patients was 82 months. Overall, younger patients survived longer than older ones. In fact, in patients > and < or = 66 years, median survival was 31 and 44 months (P < 0.00095) and the percentage of patients surviving over 72 months was 17% and 32% (P = 0.0018) respectively; in patients < 55 years, these figures were 57 months and 35% respectively (P = 0.02 and 0.01, with respect to patients aged > 55 years). In all groups, about 50% of the patients surviving over 72 months had stage I disease. For multiple myeloma patients treated with chemotherapy, survival is favourably affected by relatively young age and early stage of disease.
PMCID: PMC2151281  PMID: 9472648
3.  Serum amyloid A protein concentration in bone marrow transplantation for beta thalassaemia. 
Journal of Clinical Pathology  1992;45(4):348-351.
AIMS: To investigate whether serum amyloid A protein (SAA) and C-reactive protein (CRP) concentrations could be used in the management of beta thalassaemic patients undergoing bone marrow transplantation (BMT). METHODS: Serum SAA and CRP concentrations were determined in paired samples from 66 patients with beta thalassaemia before and after BMT. Serum SAA concentrations were determined by an enzyme linked immunoassay (EIA); serum CRP concentrations were determined by a nephelometric assay. RESULTS: Serum SAA concentrations before transplantation were significantly higher in the group that subsequently rejected the transplant than the group without complications. SAA concentrations increased after BMT in acute graft versus host disease (GvHD) and rejection. No significant increase in SAA or CRP was found in chronic GvHD. Increases in serum in SAA and CRP concentrations were not related to concomitant infection episodes. CONCLUSIONS: The different acute phase response in acute GvHD and rejection compared with chronic GvHD suggests that different immunopathogenic mechanisms are responsible.
PMCID: PMC495278  PMID: 1577974
4.  Increased serum concentrations of tumour necrosis factor in beta thalassaemia: effect of bone marrow transplantation. 
Journal of Clinical Pathology  1992;45(1):61-65.
AIMS: Serum concentrations of tumour necrosis factor-alpha (TNF) were determined in beta thalassemic patients before and after bone marrow transplantation (BMT) to evaluate whether changes in TNF concentrations after BMT were related to immune mediated complications. METHODS: Serum TNF concentrations were determined by enzyme linked immunoassay (EIA) in paired samples from 71 patients with beta thalassemia before and after BMT. Serial samples from 13 patients were also studied for up to six months after BMT. Forty one normal healthy children matched for sex and age were studied as controls. RESULTS: beta thalassemic patients had high serum TNF concentrations before transplantation compared with controls. These were not related to sex, age, duration of disease, number of blood transfusions, transferrin concentrations or splenectomy. DQw1 positive patients showed significantly lower TNF concentrations than non-DQw1 cases. Patients with severe liver fibrosis had significantly higher TNF concentrations. No correlation was found between TNF values and BMT outcome before transplantation but TNF alpha values fell significantly after BMT. The decrease persisted only in patients with successful engraftment. In serial samples studied for up to six months after BMT, TNF values decreased but in four out of five patients with graft rejection and in all five with acute graft versus host disease (GVHD) sharp increases occurred at the time of clinical symptoms. No correlation was found between the degree of GVHD and serum TNF-alpha concentrations nor between TNF-alpha concentrations after BMT and the presence of bacterial, viral, and fungal infections. CONCLUSIONS: About 50% of beta thalassemic patients have increased serum TNF, and the changes after BMT are related to the occurrence of immune mediate complications. The persistence of low TNF concentrations after successful engraftment may be due to the preparative regimen and the lack of adverse immune reactions.
PMCID: PMC495819  PMID: 1740519
5.  Novel antibiotic resistance transfer in Bacteroides. 
Resistance to tetracycline and lincosamide antibiotics was transferred en bloc from a strain of Bacteroides fragilis (V503) to a plasmidless strain of Bacteroides uniformis (V528) during in vitro filter matings. Resistance transfer was detected at frequencies of 10(-5) to 10(-6) drug-resistant progeny per input donor cell and was dependent on cell-to-cell contact of donors and recipients. Transfer was insensitive to DNase and was not mediated by chloroform- or filter-sterilized donor broth cultures. A determinant for resistance to cefoxitin in V503 was not transferred in this system. V503 contained a 3.7 x 10(6)-dalton plasmid (pVA503). Drug-resistant progeny of V503 x V528 matings usually contained pVA503, but up to 20% of the total progeny of such crosses were plasmid free. Filter blot DNA hybridization studies (Southern method) confirmed that pVA503 was not integrated into the host chromosome of the plasmidless progeny. Drug-resistant progeny from V503 x V528 matings (with or without pVA503) conjugally transferred clindamycin resistance an tetracycline resistance to a suitable recipient strain. None of the drug resistance determinants of V503 were affected by treatment with standard plasmid curing regimens, and methods designed to detect very large plasmid molecules failed to suggest the involvement of extrachromosomal DNA in this resistance transfer system. The well-characterized Bacteroides R plasmid, pBF4 (conferring clindamycin resistance), was found to share hybridizing sequences with bulk cellular V503 DNA when examined by filter blot hybridization. Similarly sized sequences were found in drug-resistant progeny recovered from matings. Neither of the two pBF4 derivatives carrying deletions that abolished clindamycin resistance hybridized with V503 DNA.
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PMCID: PMC181837  PMID: 7081969

Results 1-5 (5)