Biomedical subjects

R E Champlin

Publications and source records attributed to R E Champlin.

At least 55 records · Page 3Linked to original sources

PubMed2001

HER-2/neu overexpression as a poor prognostic factor for patients with metastatic breast cancer undergoing high-dose chemotherapy with autologous stem cell transplantation.

PURPOSE: High-dose chemotherapy with autologous stem cell transplantation (HDCT) produces a high tumor response rate for patients with metastatic breast cancer and have 20% long-term progression-free survival. Overexpression of HER-2/neu oncoprotein predicts outcome in patients with breast cancer given standard-dose chemotherapy. Therefore, we evaluated whether the HER-2/neu overexpression in the primary tumor predicts clinical outcome in patients with metastatic breast cancer given HDCT. EXPERIMENTAL DESIGN: A total of 236 patients were given standard-dose induction chemotherapy followed by stem cell collection; high-dose chemotherapy with cyclophosphamide, thiotepa, and carmustine; and stem cell infusion. HER-2/neu expression was assessed by immunostaining with anti-HER-2/neu e2-4001 monoclonal antibody in 63 patients. RESULTS: Clinical characteristics and survival were similar for patients with known and unknown HER-2/neu status. HER-2/neu was overexpressed in 22 of 63 tumors (35%). There was some tendency for HER-2/neu overexpression to be associated with the absence of estrogen or progesterone receptors. In considering the association of HER-2/neu expression with patient outcomes, HER-2/neu overexpression was associated with generally shorter overall survival (P = 0.02) and progression-free survival (P < 0.01), and this association persisted to a lesser extent after adjustment for differences in important prognostic factors between the two groups. CONCLUSION: We conclude that HER-2/neu overexpression may represent an additional prognostic factor for patients with metastatic breast cancer who undergo HDCT.

Antibodies, Monoclonal↗

PubMed2000

Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT).

Peripheral blood cells are increasingly used in place of bone marrow as a source of hematopoietic stem cells for allogeneic transplantation. The relative efficacy of these 2 approaches is unknown. This retrospective multivariate analysis compared results of 288 HLA-identical sibling blood stem cell transplantations with results of 536 HLA-identical sibling bone marrow transplantations. No transplants were T-cell depleted. Median follow-up was 12 months, and analyses focused on 1-year outcomes. Recipients of blood stem cell transplants had more rapid recovery of neutrophils to at least 0.5 x 10(9)/L (median time to recovery, 14 days, compared with 19 days for marrow transplants; P <.001) and of platelets to at least 20 x 10(9)/L (median time, 18 days, compared with 25 days for marrow transplants; P <.001). There was no significant difference in the incidence of grades II to IV acute graft versus host disease (GVHD). The incidence of chronic GVHD was significantly higher after blood stem cell transplantation (1-year probability [95% confidence interval], 65% [56%-72%] compared with 53% [47%-59%]; P =.02) Relapse incidence in the 2 transplant groups did not differ significantly. Treatment-related mortality rates were lower and leukemia-free survival rates were higher with blood stem cell transplants in patients with advanced leukemia (acute leukemia in second remission or chronic myelogenous leukemia in accelerated phase) but not in early leukemia (acute leukemia in first remission or chronic myelogenous leukemia in chronic phase). The median time from transplantation to hospital discharge was 23 days after blood stem cell transplantation and 28 days after bone marrow transplantation (P =.003). Further study with longer follow-up is necessary to definitively establish the role of blood stem cells for allogeneic transplantation, especially in patients with good-risk disease. (Blood. 2000;95:3702-3709)

Acute Disease↗

PubMed2000

T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities.

T-cell depletion of donor marrow decreases graft-versus-host disease resulting from transplants from unrelated and human leukocyte antigen (HLA)-mismatched related donors. However, there are diverse strategies for T-cell-depleted transplantation, and it is uncertain whether any improve leukemia-free survival (LFS). To compare strategies for T-cell-depleted alternative donor transplants and to compare T-cell depleted with non-T-cell-depleted transplants, we studied 870 patients with leukemia who received T-cell-depleted transplants from unrelated or HLA-mismatched related donors from 1982 to 1994. Outcomes were compared with those of 998 non-T-cell-depleted transplants. We compared LFS using different strategies for T-cell-depleted transplantation considering T-cell depletion technique, intensity of pretransplant conditioning, and posttransplant immune suppression using proportional hazards regression to adjust for other prognostic variables. Five categories of T-cell depletion techniques were considered: narrow-specificity antibodies, broad-specificity antibodies, Campath antibodies, elutriation, and lectins. Strategies resulting in similar LFS were pooled to compare T-cell-depleted with non-T-cell-depleted transplants. Recipients of transplants T-cell depleted by narrow-specificity antibodies had lower treatment failure risk (higher LFS) than recipients of transplants T-cell depleted by other techniques. Compared with non-T-cell-depleted transplants (5-year probability +/- 95% confidence interval [CI] of LFS, 31% +/- 4%), 5-year LFS was 29% +/- 5% (P = NS) after transplants T-cell depleted by narrow-specificity antibodies and 16% +/- 4% (P <.0001) after transplants T-cell depleted by other techniques. After alternative donor transplantation, T-cell depletion of donor marrow by narrow-specificity antibodies resulted in LFS rates that were higher than those for transplants T-cell depleted using other techniques but similar to those for non-T-cell-depleted transplants. (Blood. 2000;95:3996-4003)

Adolescent↗

PubMed2000

Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma.

BACKGROUND: Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy. PATIENTS AND METHODS: Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests. RESULTS: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy. CONCLUSIONS: No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.

Adult↗

PubMed2000

Importance of radiation therapy for breast cancer patients treated with high-dose chemotherapy and stem cell transplant.

PURPOSE: To determine local-regional failure rates in breast cancer patients treated with surgery and high-dose chemotherapy with stem cell transplant and to relate local-regional failure to the use and timing of radiation treatment. METHODS AND MATERIALS: We retrospectively reviewed the records of 165 breast cancer patients treated on institutional protocols with surgery and high-dose chemotherapy with stem cell transplant. All patients had either Stage III disease, 10 or more positive axillary lymph nodes, or 4 or more positive axillary lymph nodes following neoadjuvant chemotherapy. Twelve patients had inflammatory breast cancer. Thirteen patients treated with breast preservation and 5 patients who died from toxicity within 30 days of transplant were excluded from the analyses of local-regional recurrences. In the remaining 147 patients, 108 were treated with adjuvant radiation and 39 were not. The disease stage distribution for these two groups was comparable. The median follow-up for surviving patients was 35 months. RESULTS: The 3- and 5-year actuarial disease-free survival (DFS) for the entire group was 60% and 51%, respectively. The 5-year rates of freedom from isolated local-regional recurrence were 95% in the patients treated with adjuvant radiation and 86% in the patients who did not receive radiation (p = 0.014, log rank comparison). The 5-year rates of any local-regional recurrence as a first event (isolated recurrences plus those with simultaneous local-regional and distant recurrences) were 92% versus 82%, respectively for patients whose treatment did and did not include radiation (p = 0.038). We could not demonstrate a correlation of the timing of radiation with the risk of local-regional recurrence. CONCLUSIONS: These data indicate that high-dose chemotherapy does not negate the importance of radiation in optimizing local-regional control in patients with high-risk breast cancer. Given the results of recent randomized trials studying postmastectomy radiation, which show that improving local-regional control improves overall survival (OS), we believe that all breast cancer patients with high-risk primary breast cancer who are treated with high-dose chemotherapy with stem cell transplant should receive radiation as a component of their treatment.

Adult↗

PubMed2000

Management of cancer treatment-related diarrhea. Issues and therapeutic strategies.

The cancer treatment-related diarrhea caused by acute graft-versus-host disease (GVHD) and chemotherapeutic agents, particularly fluoropyrimidines and irinotecan, significantly affects patient morbidity and mortality. The mechanisms causing cancer treatment-related diarrhea are not fully understood, but histopathologic evidence points to a multifactorial process that causes an absorptive and secretory imbalance in the small bowel. Cancer treatment-related diarrhea could be life-threatening, yet assessment and treatment are not currently standardized. Several clinicians participated in a closed roundtable meeting to review the mechanisms of chemotherapy-induced diarrhea (CID) and GVHD-induced diarrhea, management issues in cancer treatment-induced diarrhea, and pharmacologic approaches to treatment. The meeting produced a proposal for new treatment guidelines and an algorithm, which include the use of octreotide for the management of CID- and GVHD-induced diarrhea. The development of diarrhea assessment guidelines that expand on the current National Cancer Institute criteria and allow for better patient management was also proposed.

Antineoplastic Agents↗

PubMed2000

Status of high-dose chemotherapy for breast cancer: a review.

The purpose of this review is to analyze the current status of high-dose chemotherapy (HDCT) with autologous stem cell transplantation for patients with breast cancer. Current results from the major prospective phase 2 and phase 3 trials in metastatic breast cancer (MBC) and high-risk primary breast cancer (HRPBC) are reviewed. Prognostic factors and future research directions are also discussed. The encouraging results of phase 2 trials suggested a benefit for HDCT in HRPBC and some categories of patients with MBC. Some investigators have argued that patient selection might have been a critical factor in those studies. Recently reported randomized trials in patients with chemosensitive MBC have included only small numbers of patients in complete remission and thus have not adequately addressed the relative value of HDCT versus maintenance standard-dose chemotherapy in this patient subset. Although initial results of 2 studies have been reported, most randomized phase 3 studies of HDCT in HRPBC require longer follow-up before definitive conclusions can be made about its efficacy in this setting. We conclude that the role of HDCT for HRPBC or MBC patients has not yet been fully defined. Longer follow-up of the ongoing randomized trials is necessary, and their mature results will help clarify this important question. In the meantime, it is imperative that research continues, to enhance the efficacy of the procedure. This may come through incorporating more active drugs into HDCT regimens and combining HDCT with novel strategies aimed at eradication of posttransplantation minimal residual disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Acute safety and pharmacokinetics of intravenous busulfan when used with oral busulfan and cyclophosphamide as pretransplantation conditioning therapy: a phase I study.

The unpredictable intestinal absorption and erratic bioavailability of oral busulfan (Bu) has limited the drug's use in high-dose pretransplantation conditioning therapy. To standardize drug delivery, we solubilized Bu for parenteral use. This new intravenous (i.v.) Bu formulation was combined with oral Bu and cyclophosphamide (Cy) to evaluate (1) the human acute toxicity of i.v. Bu and its solvent system and (2) the pharmacokinetics of Bu in patients undergoing hematopoietic progenitor cell transplantation (HPCT). One dose of i.v. Bu (escalating from 0.08 to 0.8 mg/kg) was given over 2 hours by pump; 6 hours later, an oral Bu regimen was begun, consisting of 1 mg/kg every 6 hours for 15 doses, followed by Cy, 60 mg/kg daily for 2 days. After 1 day of rest, HPCT was performed. The i.v. Bu dose was well tolerated and did not produce any acute toxicity reaction that could be attributed to the solvent system of dimethylacetamide and polyethylene glycol (PEG)-400. All observed treatment-related toxicity was as would be expected after high-dose oral Bu plus Cy. When the i.v. Bu was used as reference solution, the pharmacokinetic analysis indicated an average bioavailability of oral high-dose Bu of 69%, ranging from <10% to virtually 100%. Further, the 2-hour infusion of i.v. Bu gave a time to maximum plasma concentration following drug administration similar to that of oral Bu (2 hours and 1.8 hours, respectively), and i.v. Bu had a clearance similar to that of oral Bu. Based on the data in this study, we suggest that the optimal (starting) dose of i.v. Bu (in combination with Cy) in our forthcoming phase 2 trial should be on the order of 0.8 mg/kg to target an area under the curve (AUC) of 1100 to 1200 micromol/L per minute. This would secure myeloablation and engraftment but save the vast majority of patients from the increased risk of serious hepatic veno-occlusive disease that has been reported when the AUC level exceeds 1500 micromol/L per minute. Bu administration via the i.v. route will assure complete bioavailability and reliable systemic drug exposure with more predictable blood levels and, therefore, possibly lower the risks for serious/life-threatening toxicity, graft rejection, and recurrent leukemia.

Acetamides↗

PubMed2000

Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia.

Although the immune system has long been implicated in the control of cancer, evidence for specific and efficacious immune responses in human cancer has been lacking. In the case of chronic myelogenous leukemia (CML), either allogeneic bone marrow transplant (BMT) or interferon-alpha2b (IFN-alpha2b) therapy can result in complete remission, but the mechanism for prolonged disease control is unknown and may involve immune anti-leukemic responses. We previously demonstrated that PR1, a peptide derived from proteinase 3, is a potential target for CML-specific T cells. Here we studied 38 CML patients treated with allogeneic BMT, IFN- alpha2b or chemotherapy to look for PR1-specific T cells using PR1/HLA-A*0201 tetrameric complexes. There was a strong correlation between the presence of PR1-specific T cells and clinical responses after IFN-alpha and allogeneic BMT. This provides for the first time direct evidence of a role for T-cell immunity in clearing malignant cells.

Blood Circulation↗

PubMed2000

Respiratory syncytial virus upper respiratory tract illnesses in adult blood and marrow transplant recipients: combination therapy with aerosolized ribavirin and intravenous immunoglobulin.

Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in blood and marrow transplant (BMT) recipients. In some subsets of these immunocompromised patients, RSV upper respiratory illnesses frequently progress to fatal viral pneumonia. The frequency of progression to pneumonia is higher during the pre-engraftment than during the post-engraftment period. Once pneumonia develops, the overall mortality is 60-80%, regardless of the treatment strategy. We performed a pilot trial of therapy of RSV upper respiratory illnesses using aerosolized ribavirin and IVIG (500 mg/kg every other day), with the goal of preventing progression to pneumonia and death. Two dosages of ribavirin were used: a conventional regimen (6 g/day at 20 mg/ml for 18 h/day) and a high-dose short-duration regimen (6 g/day at 60 mg/ml for 2 h every 8 h). Fourteen patients were treated for a mean of 13 days (range: 7-23 days). In 10 (71%) patients, the upper respiratory illness resolved. The other four (29%) patients, three of whom were in the pre-engraftment period, developed pneumonia, which was fatal in two. The most common adverse effect was psychological distress at being isolated within a scavenging tent. In conclusion, prompt therapy of RSV upper respiratory illnesses in BMT recipients with a combination of aerosolized ribavirin and IVIG was a safe and promising approach to prevent progression to pneumonia and death.

Adult↗

PubMed2000

Bronchoalveolar lavage in the diagnosis of pulmonary complications of bone marrow transplant patients.

Bronchoalveolar lavage (BAL) has proved valuable in the diagnosis of pulmonary complications in immunosuppressed patients. We evaluated the diagnostic yield of BAL in pulmonary complications in bone marrow transplantation (BMT) recipients. We reviewed sequentially the records of 89 patients during an 18-month period. BAL was diagnostic in 42 patients (47%). The most common pulmonary complication diagnosed by BAL was diffuse alveolar hemorrhage (n = 15); followed by bacterial pneumonia (n = 10), respiratory syncytial virus (n = 8), aspergillosis (n = 6), Pneumocystis carinii pneumonia (n = 5), cytomegalovirus (CMV) (n = 4), and others (n = 4). The final diagnoses in the BAL non-diagnostic group were: bacterial pneumonia (n = 6), CMV (n = 6), idiopathic pneumonia syndrome (n = 5), cancer recurrence (n = 4), cardiogenic pulmonary edema (n = 4), and others (n = 9). We conclude that BAL is a useful diagnostic tool in BMT-related pulmonary complications.

Bone Marrow Transplantation↗

PubMed2000

Allogeneic stem cell transplantation (BMT) for AML and MDS following i.v. busulfan and cyclophosphamide (i.v. BuCy).

Pretransplant conditioning therapy with i.v. BuCy followed by allogeneic hematopoietic stem cell transplantation (BMT) was investigated in a phase II trial in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We gave i.v. Bu at a dose of 0.8 mg/kg every 6h x 16 doses, followed by Cy 60 mg/kg daily for 2 days. Twenty-six AML patients (18 males/eight females) were treated, only eight of whom were in CR1. The rest were either refractory to induction chemotherapy (four patients) or in a more advanced stage of their disease (14 patients). In addition, nine patients with MDS (1M/8F) were treated. Their median age was 41 years (range 21-64). Engraftment to > or =500 neutrophils/microl was reached at 14 days (range 10-29 days) post BMT, and the median time of neutropenia was only 11 days (range 4-28 days). The most common regimen-related toxicity was grade 2-3 nausea. In the post-BMT period (including BMT day +30), two patients died, one each from pulmonary hemorrhage secondary to CMV pneumonia and hepatic veno-occlusive disease (VOD), for an early treatment-related mortality (TRM) of 5.7%. Three patients developed VOD and two of them died. There was no direct regimen-related pulmonary or neurologic toxicity. Overall, the clinical side-effect spectrum was analogous to what would be expected from a high-dose oral Bu-based regimen; there was no unique toxicity experienced with the used solvent system. The disease-free survival in the high-risk subgroup (all patients not in CR1) at 1 and 2 years post transplant was 44% and 31%, respectively. The 13 patients still alive in CR have been followed for a median of 24 months (range 18-32). Pharmacokinetic analysis showed very good interdose reproducibility, and limited interpatient variability in area under the plasma concentration vs time curve, peak concentration, and clearance of Bu after this i.v. formulation. We conclude, that this new i.v. Bu formulation is well tolerated; it has an impressive safety profile, and we suggest that it should be considered as appropriate replacement for oral busulfan in pretransplant conditioning therapy prior to allogeneic BMT for patients with AML or MDS.

Administration, Oral↗

PubMed2000

High-dose ifosfamide and etoposide with filgrastim for stem cell mobilization in patients with advanced ovarian cancer.

High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation has shown promise as treatment for recurrent or persistent epithelial ovarian cancer. We evaluated the stem cell mobilization regimen of high-dose ifosfamide plus etoposide in 32 patients with epithelial ovarian cancer, who had a positive second-look laparatomy or recurrent disease. Ifosfamide was given at 10 g/m2 by continuous i.v. from days 1 to 3. Etoposide was given at 150 mg/m2 every 12 h for six doses on days 1-3. Filgrastim was given at 10 microg/kg/d s.c. from day 5 until the completion of peripheral blood stem cell harvest. Fourteen of 32 patients had measurable or evaluable disease before mobilization therapy and were assessed for response. In nine (64%) of the 14 patients, treatment response was demonstrated, and these patients received a second cycle of mobilization therapy. The target CD34+ cell dose (>8 x 106 cells/kg) was achieved with a median of one apheresis (range 1-5). A median of 25.1 (range 8.0-122.5) x 106 CD34+ cells/kg body weight was collected. Non-hematologic toxicity was limited to grade 2 renal dysfunction in one patient and grade 2 hepatic dysfunction in three patients. In this patient group, high-dose ifosfamide plus etoposide with filgrastim support was well tolerated, lead to successful stem cell harvest and had antitumor activity.

Adult↗

PubMed2000

Allogeneic stem cell transplantation with fludarabine-based, less intensive conditioning regimens as adoptive immunotherapy in advanced Hodgkin's disease.

Six patients with advanced Hodgkin's disease in which multiple conventional treatments (median prior chemotherapy regimens: seven), radiation therapy, and a prior autologous stem cell transplantation (SCT) had failed underwent allogeneic SCT following a fludarabine-based conditioning regimen. Median age was 29 years (22-30). Median time to progression after autologous SCT was 6 months (4-21). Disease status at transplant was refractory relapse (n = 3) and sensitive relapse (n = 3). Cell source was filgrastim-mobilized peripheral blood stem cells from an HLA-identical sibling (n = 4) or matched unrelated donor marrow (n = 2). Conditioning regimens were fludarabine-cyclophosphamide-antithymocyte globulin (n = 4), fludarabine-melphalan (n = 1) and fludarabine-cytarabine-idarubicin (n = 1). Myeloid recovery was prompt, with an absolute neutrophil count > or =500/microl on day 12 (11-15). Median platelet recovery to > or =20000/microl was on day 9 (0-60). Chimerism studies on day 30 indicated 100% donor-derived hematopoiesis in 4/5 evaluable patients (4/4 non-progressors). All responders (3/3) have ongoing 100% donor-derived chimerism. Acute graft-versus-host disease (GVHD) was diagnosed in 4/6 evaluable patients. Chronic GVHD was present in 2/4 evaluable patients. There were no regimen-related deaths. Overall day 100 transplant-related mortality was 2/6 (33%). Three patients have expired and three are alive and progression-free with a median follow-up of 9 months (6-26) post transplant. We conclude that allogeneic stem cell transplantation with fludarabine-based preparative regimens is feasible in these high-risk, heavily pretreated HD patients.

Adult↗

PubMed2000

A comparative study of once-daily versus twice-daily filgrastim administration for the mobilization and collection of CD34+ peripheral blood progenitor cells in normal donors.

Eighty-one first-time normal donors underwent leukapheresis for peripheral blood progenitor cell (PBPC) collection after mobilization with filgrastim administered either twice-daily (6 microg/kg every 12 h; n = 40) or once-daily (12 microg/kg; n = 41) subcutaneously for 3 d. The groups were similar for age, donor blood volume and target CD34+ cell dose to be collected (>/= 4 x 106 CD34+ cells/kg recipient). There was no statistically significant difference in the apheresis yield of CD34+ PBPCs (x 106) per kg recipient weight (5.6 +/- 3.3 vs. 5.6 +/- 4.3; P = 0.94) and per litre of blood processed (30 +/- 17.2 vs. 30.4 +/- 19.5; P = 0.92).

Adult↗

PubMed2000

Allogeneic haematopoietic transplantation for Richter's syndrome.

This study evaluated the efficacy of allogeneic bone marrow transplantation (AlloBMT) in eight patients who had chronic lymphocytic leukaemia (CLL) in Richter's transformation. Five patients were in resistant relapse and three others were in sensitive or untreated relapse. Three out of eight patients (38%) were alive and in remission at 14 months, 47 months and 67 months respectively. Two of these three patients, including one with an unrelated-donor transplant and a prior, unsuccessful autologous transplantation, received a non-myeloablative preparative regimen. These data suggest that, compared with conventional chemotherapy, AlloBMT improves the prognosis for patients with Richter's syndrome. Further study of a larger number of patients is needed to confirm these results.

Adult↗

PubMed2000

Role of tumor necrosis factor-alpha inhibition with inflixiMAB in cancer therapy and hematopoietic stem cell transplantation.

Tumor necrosis factor (TNF)-alpha is a central cytotoxic and proinflammatory cytokine. Research on the benefits of TNF-alpha inhibition as a form of therapy has focused almost exclusively on autoimmune, inflammatory disorders. InflixiMAB, a chimeric antibody to human TNF-alpha, was recently approved for the management of Crohn disease and rheumatoid arthritis. The potential applications of inflixiMAB in the management of cancer are just beginning to be explored. This article reviews the biology, mechanism of action, pharmacology, and toxicity of inflixiMAB. Existing clinical experience and inflixiMAB's potential role as an immunosuppressant and antitumor agent in the management of cancer are also discussed.

Antibodies, Monoclonal↗

PubMed2000

Outcome of bone marrow transplantation patients requiring mechanical ventilation.

OBJECTIVE: To identify outcome predictors in bone marrow transplantation (BMT) patients admitted to the intensive care unit (ICU) of The University of Texas M. D. Anderson Cancer Center who required endotracheal intubation and mechanical ventilation. DESIGN: Retrospective, comparative study. SETTING: A 16-bed medical intensive care unit in a university teaching cancer center. PATIENTS: The records of 60 consecutive BMT patients who developed respiratory failure requiring mechanical ventilation were reviewed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The most frequent complication leading to respiratory failure was pneumonia (41%) followed by diffuse alveolar hemorrhage (37%). Eighteen percent of the patients were extubated and discharged from the ICU, but only 5% were alive at 6 months. Graft vs. host disease was a predictor of a poor outcome (p < .05). Breast cancer as an underlying disease and pulmonary edema as a complication were favorable predictive factors (p < .05). Five of 26 patients with diffuse alveolar hemorrhage and four of 33 patients with pneumonia survived. We found no relationship between survival and age, gender, BMT type, or Acute Physiology and Chronic Health Evaluation II score. Prolonged mechanical ventilation (> or =15 days) and late development of respiratory failure (>30 days after BMT) were associated with poor prognosis. CONCLUSIONS: The ICU survival rate of BMT patients who developed pulmonary complications and required mechanical ventilation was 18%. Prognostic factors were described identifying patients with a substantial survival rate as well as those in whom mechanical ventilation was futile.

APACHE↗