A prospective study was undertaken to compare the mononuclear cell, CD34+ cell, and CFU-GM yields of the Haemonetics MCS-3P and the Cobe Spectra cell separators in ten patients (nine multiple myeloma and one non-Hodgkin lymphoma) on two consecutive days after mobilization with high-dose filgrastim (12-16 micrograms/k) for 4 days. All patients were harvested once on each machine, five starting on each machine. The target duration of the procedure on the Spectra was 160 minutes, and the target blood volume processed on the MCS-3P was 60-70 ml/kg body weight. Both machines were operating on the 1995 software versions supplied by the respective manufacturers. The time taken for the procedure was significantly longer with the Haemonetics machine. The volumes of blood processed and the product collected were significantly higher with the Spectra, as were the absolute mononuclear and CD34+ cell yields, and yields per unit time. Mononuclear and CD34+ cell yields per unit volume of blood processed were comparable for both machines. The differences in CFU-GM yields were not significant, largely because of wide interpatient variations. The extent of platelet depletion as a result of the procedure was greater with the Spectra because of the higher blood volume being processed. We conclude that the Cobe Spectra is a significantly faster machine than the Haemonetics MCS-3P; and consequently, its use is associated with higher mononuclear and CD34+ cell yields.

Antigens, CD34↗

PubMed1997

Comparison of marrow vs blood-derived stem cells for autografting in previously untreated multiple myeloma.

Sixty-three new untreated patients with multiple myeloma under the age of 70 years received C-VAMP induction treatment followed by high-dose intravenous melphalan (200 mg m(-2)) and autologous stem cell transplant, either with marrow [autologous bone marrow transplants (ABMT), n = 26] or with granulocyte colony-stimulating factor (G-CSF)-mobilized stem cells from the blood [peripheral blood stem cell transplants (PBSCT), n = 37]. This was a sequential study and the two groups were not significantly different for all known prognostic variables. The complete remission (CR) rate after high-dose treatment was the same for both groups [ABMT 84% and PBSCT 70%; P = not significant (NS)]. Neutrophil recovery to 0.5 x 10(9) l(-1) occurred at a median of 22 days in the ABMT patients compared with 19 days for the PBSCT patients (P = NS). Platelet recovery to 50 x 10(9) l(-1) was significantly faster in PBSCT patients (19 days vs 33 days; P = 0.0015), and the PBSCT patients spent fewer days in hospital (median 20 vs 27 days; P = 0.00001). There was no difference in the two groups with respect to starting interferon (58 days for ABMT vs 55 days for PBSCT), and tolerance to interferon was identical. The median overall survival (OS) and progression-free survival (PFS) for the PBSCT patients has not yet been reached. The OS in the ABMT patients at 3 years was 76.9% (95% CI 60-93%) compared with 85.3% (95% CI 72-99%) in the PBSCT patients (P = NS), and the PFS at 3 years in the ABMT patients was 53.8% (95% CI 34-73%) and in the PBSCT patients was 57.6% (95% CI 34-81%) (P = NS). The probability of relapse at 3 years was 42.3% in the ABMT arm compared with 40% in the PBSCT patients (P = NS). Thus, PBSCT patients had a faster engraftment and a shorter stay in hospital than ABMT; the survival outcome and probability of relapse was the same for both groups.

Adult↗

PubMed1997

Outcome assessment of a population-based group of 195 unselected myeloma patients under 70 years of age offered intensive treatment.

A single centre series of 195 consecutive newly diagnosed untreated myeloma patients under 70 years, seen between September 1986 and March 1994, were analysed to assess the impact of current intensive treatment methods upon remission rate, response rate and subsequent outcome. They were predominantly an unselected population based group of patients (other than by age) that could be used by purchasers of health care as a model for outcome assessment. All patients were scheduled to receive a care plan which included a sequential package of treatment consisting initially of courses of infusional chemotherapy using vincristine, adriamycin and methyl prednisolone (VAMP) and 90 of these also received cyclophosphamide (C-VAMP). Thirty-eight patients received verapamil in addition to C-VAMP(V-C-VAMP). After VAMP all patients were planned to receive high-dose treatment with melphalan 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 treatment because of refusal, resistant disease, poor performance or treatment-related death. The patients who received melphalan or busulfan alone instead of high-dose melphalan/autografts did so because of increasing age (P = 0.001) and a raised creatinine (P = 0.05). The complete remission rate was 53% for the whole group and 74% for those receiving high-dose melphalan and an autograft. From July 1988, the sequential therapy package included continuous three times weekly interferon (IFN) after high-dose treatment as maintenance therapy, initially as part of a controlled randomised trial and then for all suitable patients. Fifty-seven patients received IFN. The median overall survival (OS) and progression-free survival (PFS) from first treatment for the whole group of 195 patients is 4.5 years and 25 months, respectively. The 112 patients receiving the melphalan autografts fared significantly better than the rest of the patients with OS and PFS (from high-dose treatment) of 6.6 years and 27 months, respectively (P < 0.005), and the 57 patients also receiving IFN have a OS yet to reach a median at 8 years and a PFS of 44 months, significantly better than non IFN high-dose patients (P < 0.0036). However, although we showed benefit for selected patients in studies and trials (particularly with IFN) during the 8-year period of the series, this did not translate into overall PFS benefit in our study for unselected cohorts of patients for 1986-1988 (64 patients) 1989-1992 (100 patients) and 1992-1994 (34 patients) in spite of progressive increases in the proportion of patients receiving IFN (respectively 6, 35 and 58%). This is likely to be due to the dilution of benefit to specific patients by the overall number of patients involved. Outcome data from unselected patients are now expected by purchasers and presented in this way, help qualify the activity impact of advances made from research trials for the treatment of population-based cancer problems.

Adult↗

PubMed1997

Donor lymphocyte infusion for childhood acute lymphoblastic leukaemia relapsing after bone marrow transplantation.

Four children with acute lymphoblastic leukaemia (ALL) who relapsed after allogeneic bone marrow transplantation (BMT) were treated with donor lymphocyte infusion (DLI) without prior conditioning. Three patients had previously received a non-T-cell-depleted matched sibling BMT and the fourth had a T-cell-depleted matched unrelated BMT. Two patients developed grade III-IV acute graft-versus-host-disease (GVHD) of the skin, which required intervention. Both are alive in complete haematological remission 7 and 10 months from DLI with chronic GVHD of the skin requiring immunosuppressive therapy. A third patient went into haematological remission 6 weeks after DLI, but with no clinical evidence of GVHD. His bone marrow remained in remission 11 months post-DLI despite the disease (ALL) relapsing in extramedullary sites. The fourth patient showed no clinical or haematological response to three consecutive doses of DLI given at 4-weekly intervals and died from progressive disease 11 months after relapse. These preliminary observations indicate that in constrast to experience in adult ALL, DLI may be effective in inducing sustained remission in children with ALL relapsing after BMT, and a response may occur even in the absence of clinical evidence of GVHD.

Adolescent↗

PubMed1997

A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C-VAMP) as induction treatment followed by autografting in previously untreated myeloma.

In a sequential nonrandomized study, 204 consecutive unselected patients aged < 70 years received induction chemotherapy with infusional vincristine and adriamycin with oral methyl prednisolone (VAMP: n = 75) or with additional cyclophosphamide, C-VAMP (n = 129). 38/129 C-VAMP patients also received verapamil during induction as part of a controlled trial with the aim to overcome drug resistance. A median of five courses (range 1-11) of chemotherapy were required before maximal response was attained and this was similar in both groups. An over-all response rate of 71% was noted at the end of induction. The complete remission (CR) rate with C-VAMP was 24%, which was significantly higher (P = 0.04) than the CR rate with VAMP alone (8%). The addition of verapamil did not alter the response rate of C-VAMP. Compliance to VAMP was overall 83% and not affected by the addition of cyclophosphamide. The proportion of patients going on to receive high-dose chemotherapy and an autograft was the same for VAMP and C-VAMP treated patients (71%). The median overall survival (OS) and progression-free survival (PFS) for the whole group were 4.4 years and 2.0 years and no difference in outcome was observed between the different treatment groups. Therefore the addition of weekly cyclophosphamide to VAMP induction therapy has significantly improved the response rates of previously untreated myeloma patients. C-VAMP was not more toxic and did not compromise the chances of receiving an autograft. Verapamil was without influence on any parameters in this study.

Adult↗

PubMed1997

Prediction of outcome from intensive care: a prospective cohort study comparing Acute Physiology and Chronic Health Evaluation II and III prognostic systems in a United Kingdom intensive care unit.

OBJECTIVE: To evaluate the ability of two prognostic systems to predict hospital mortality in adult intensive care patients. DESIGN: Prospective cohort study. SETTING: A mixed medical and surgical intensive care unit (ICU) in the United Kingdom. PATIENTS: A total of 1,144 patients consecutively admitted to the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute Physiology and Chronic Health Evaluation (APACHE) II and III prognostic systems were applied to assess probabilities of hospital mortality, which were compared with the actual outcome. The overall goodness-of-fit of both models was assessed. Hospital death rates were higher than those predicted by each system. Risk estimates showed a strong positive correlation between both systems (nonsurvivors r2 = 0.756, p < .0001; survivors r2 = 0.787, p < .0001). Calibration of APACHE II (chi 2 = 98.6, Lemeshow-Hosmer) was superior to that of APACHE III (chi 2 = 129.8, Lemeshow-Hosmer). The total correct classification rate of APACHE III was greater for all decision criteria applied; the best overall total correct classification rate was 80.6% for APACHE III and 77.9% for APACHE II (both for a decision criterion of 40%). The areas under the receiver operating characteristic curves were 0.806 and 0.847 for APACHE II and III, respectively, confirming the better discrimination of APACHE III. When patients were classified by diagnostic categories, risk predictions did not fit uniformly across the spectrum of disease groups. For both models, mortality ratios were highest for trauma patients and lowest for the group with respiratory disease. APACHE II predictions for patients with gastrointestinal disease were significantly better. Risk estimates for surgical admissions were superior with APACHE II (MR = 1.27) compared with APACHE III (MR = 1.56), but were similar for medical patients (1.22 vs. 1.28 for APACHE II and III, respectively). Bias induced by factors reflecting the clinical practice in an individual ICU (e.g., admission criteria, treatment before admission) may have considerable impact on risk estimates. The identification of such factors appears to be a prerequisite for the meaningful interpretation of observed and predicted death rates on the individual ICU level. CONCLUSIONS: Both predictive models demonstrated a similar degree of overall goodness-of-fit. APACHE II showed better calibration, but discrimination was better with APACHE III. Hospital mortality was higher than predicted by both models, but was underestimated to a greater degree by APACHE III. Risk estimates by both models showed considerable variation across the disease spectrum of ICU patients. Risk predictions for surgical patients and patients with gastrointestinal disease were better with APACHE II. Factors reflecting the clinical practice of an individual ICU are not accounted for by APACHE II and III. Overall, the performance of APACHE III was not superior to that of its predecessor for a cohort of United Kingdom ICU patients; for certain diagnostic categories, APACHE III performed worse than APACHE II despite an improved system of disease classification.

APACHE↗

PubMed1996