Myeloma patients who are able to receive HDM plus ABMT following conventional chemotherapy achieve a high proportion of CRs, which may be associated with prolonged survival.
Summary. High-dose chemotherapy (melphalan) with autologous marrow stem cell support (AMSCS) results in high response rates in multiple myeloma (MM), with up to 50% of patients achieving complete remission. However, these remissions are generally not durable. As the cytokine interferon alpha has been shown to prolong partial response following conventional chemotherapy, this trial was conducted to evaluate its role following high-dose chemotherapy. 85 patients were randomly assigned to maintenance treatment with interferon alpha, 3 × 10 6 units/m 2 subcutaneously three times weekly until relapse or no further treatment following recovery from high-dose chemotherapy (melphalan 140-200 mg/m 2 or busulphan 16 mg/kg) combined with AMSCS. At 5·8 years following the accrual of the last patient in this trial, 38 patients had died, 17 in the interferon arm and 21 in the control arm. The median progression-free survival (PFS) in the 42 patients randomized to interferon alpha was 46 months versus 27 months in the controls. Both overall survival and PFS, which were highly significant at median follow-up of 52 months, have now ceased to be significant, because most patients have ultimately succumbed to their disease. Interferon was tolerated by the majority of patients with very good compliance. Toxicity consisted mainly of flu-like symptoms and malaise which were usually self-limiting. The results of such a pilot study should be carefully interpreted and the benefits of interferon should be confirmed in larger multicentre studies in the setting of minimal residual disease following autologous transplantation.
IL-5 is induced locally in the lung and systemically in the circulation during allergic airways eosinophilic inflammation both in humans and experimental animals. However, the precise role of local and systemic IL-5 in the development of allergic airways eosinophilia remains to be elucidated. In our current study, we demonstrate that compared with their IL-5 ϩրϩ counterparts, IL-5 Ϫ / Ϫ mice lacked an IL-5 response both in the lung and peripheral blood, yet they released similar amounts of IL-4, eotaxin, and MIP-1 ␣ in the lung after ovalbumin (OVA) sensitization and challenge. At cellular levels, these mice failed to develop peripheral blood and airways eosinophilia while the responses of lymphocytes, neutrophils, and macrophages remained similar to those in IL-5 ϩրϩ mice. To dissect the relative role of local and systemic IL-5 in this model, we constructed a gene transfer vector expressing murine IL-5. Intramuscular IL-5 gene transfer to OVA-sensitized IL-5 Ϫ / Ϫ mice led to raised levels of IL-5 compartmentalized to the circulation and completely reconstituted airways eosinophilia upon OVA challenge, which was associated with reconstitution of eosinophilia in the bone marrow and peripheral blood. Significant airways eosinophilia was observed for at least 7 d in these mice. In contrast, intranasal IL-5 gene transfer, when rendered to give rise to a significant but compartmentalized level of transgene protein IL-5 in the lung, was unable to reconstitute airways eosinophilia in OVA-sensitized IL-5 Ϫ / Ϫ mice upon OVA-challenge, which was associated with a lack of eosinophilic responses in bone marrow and peripheral blood. Our findings thus provide unequivocal evidence that circulating but not local lung IL-5 is critically required for the development of allergic airways eosinophilia. These findings also provide the rationale for developing strategies to target circulating IL-5 and/or its receptors in bone marrow to effectively control asthmatic airways eosinophilia. ( J.
No national benchmark figures exist for early mortality due to chemotherapy unlike for surgical interventions. Deaths within 30 days of chemotherapy during a 6-month period were identified from the Royal Marsden Hospital electronic patient records. Treatment intention -curative or palliative, cause of death and number of previous treatments -were documented. Between April 2005 and September 2005, 1976 patients received chemotherapy with 161 deaths within 30 days of chemotherapy (8.1%). Of these, 124 deaths (77.0%) were due to disease progression. Of the other 37 deaths, 12 (7.5%) were related to chemotherapy, six each for solid tumours and haematological malignancies, of which seven (4.3%) were due to neutropenic sepsis. For the remaining 25 deaths (15.5%) there was insufficient information. There were more deaths after third and subsequent lines of therapy than with first and secondlines of therapy. Only 12 of the 161 deaths occurred in patients who were receiving potentially curative chemotherapy to give a mortality rate in breast and gastrointestinal malignancy of 0.5 and 1.5%, respectively. It is possible to audit mortality within 30 days of chemotherapy and this should become a benchmark for standard practice nationally. Most deaths were due to disease progression in the palliative setting. We practice this form of audit each quarter and feed back to the treating teams so that deaths are discussed and practice monitored.
Summary Risk of second primary malignancy was assessed in follow-up to June 1991 of 1039 patients first treated for Hodgkin's disease at the Royal Marsden Hospital during 1963-91. A total of 77 second malignancies occurred. There were significantly raised risks of stomach [standardized incidence ratio (SIR)=4.0], lung (SIR=3.8), bone (SIR=26.5), soft tissue (SIR=1 6.9) and non-melanoma skin (SIR=3.9) cancers, non-Hodgkin's lymphoma (SIR=4.6), and acute and non-lymphocytic leukaemia (SIR=31.3), with a relative risk of 3.3 for all second cancers other than non-melanoma skin cancer. Solid cancer risk was raised to a similar extent in patients treated only with radiotherapy (SIR=2.6, P<0.001), only with chemotherapy (SIR=2.1, P=0.08) and with both (SIR=3.1, P<0.001). Leukaemia risk was raised only in those receiving chemotherapy, whether alone or with radiotherapy. The relative risk for solid cancers was much greater in patients who were younger at first treatment (trend P<0.001), whereas leukaemia risk was greatest for those first treated at ages 25-44. For solid cancers (P<0.001) but not leukaemia (P=0.05) there was a strong gradient of greater relative risks at younger attained ages. The relative risk of second cancers overall was 27.5 at ages under 25 and 2.0 at ages 55 and above. Leukaemia and solid cancer risks in patients treated with chlorambucil, vinblastine, procarbazine and prednisone (ChIVPP) were not significantly greater than those in patients treated with mustine, vincristine, procarbazine and prednisone (MOPP). Number of cycles of chemotherapy was significantly related to risk of leukaemia (P<0.001), and there was a trend in the same direction for solid cancers (P=0.07). The study adds to evidence that alkylating chemotherapy may increase the risk of solid cancers, and that ChIVPP does not provide a less carcinogenic alternative to MOPP chemotherapy. The very large relative risks found for solid cancers at young attained ages and in patients treated when young may have important implications as, in the long term, the majority of second malignancies after Hodgkin's disease are solid cancers. The risks of solid malignancies need clarification by larger collaborative epidemiological studies.
Summary:OS yet to reach a median at 8 years and a PFS of 44 months, significantly better than non IFN high-dose A single centre series of 195 consecutive newly diagpatients (P Ͻ 0.0036). However, although we showed nosed untreated myeloma patients under 70 years, seen benefit for selected patients in studies and trials between September 1986 and March 1994, were ana-(particularly with IFN) during the 8-year period of the lysed to assess the impact of current intensive treatment series, this did not translate into overall PFS benefit in methods upon remission rate, response rate and subour study for unselected cohorts of patients for 1986-sequent outcome. They were predominantly an unselec-1988 (64 patients) 1989-1992 (100 patients) and 1992-ted population based group of patients (other than by 1994 (31 patients) in spite of progressive increases in age) that could be used by purchasers of health care the proportion of patients receiving IFN (respectively 6, as a model for outcome assessment. All patients were 35 and 58%). This is likely to be due to the dilution scheduled to receive a care plan which included a of benefit to specific patients by the overall number of sequential package of treatment consisting initially of patients involved. Outcome data from unselected courses of infusional chemotherapy using vincristine, patients are now expected by purchasers and presented adriamycin and methyl prednisolone (VAMP) and 90 of in this way, help qualify the activity impact of advances these also received cyclophosphamide (C-VAMP).made from research trials for the treatment of popuThirty-eight patients received verapamil in addition to lation-based cancer problems. C-VAMP(V-C-VAMP). After VAMP all patients wereKeywords: myeloma; induction; autologous transplanplanned to receive high-dose treatment with melphalan tation; interferon; outcome assessment; population based and an autograft (marrow or blood) and 112 received this treatment; a further 29 patients received modified high-dose treatment with melphalan alone (23) or busulfan (6) and 54 (28%) did not proceed to high-dose treatSince 1980, three important and entirely different treatment because of refusal, resistant disease, poor performments for myeloma have been developed in phase II studies ance or treatment-related death. The patients who and then been shown in controlled trials to markedly received melphalan or busulfan alone instead of highimprove outcome for selected patients with myeloma; dose melphalan/autografts did so because of increasing namely infusional induction chemotherapy, 1-3 high-dose age (P = 0.001) and a raised creatinine (P = 0.05). The consolidation chemotherapy 4,5 with autologous bone marcomplete remission rate was 53% for the whole group row rescue, 6,7 and maintenance interferon. 8,9 However, the and 74% for those receiving high-dose melphalan and nature of controlled trials, with strict entry criteria, usually an autograft. From July 1988, the sequential therapy requires that patients are selected, and further selection package in...
Single-agent HDM without autologous bone marrow transplantation is a feasible therapeutic option in myeloma, and is associated with a high objective response rate, relatively long remission durations, and good symptom control.
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