melphalan and Hypotension

To evaluate feasibility and potential efficacy of amifostine (AMI) in the prevention of toxicities associated with high-dose melphalan (MEL), ten myeloma patients received AMI 910 mg/m2 in 15 min infusion preceding MEL 200 mg/m2 followed by stem cell infusion (AMI group). Hematologic and extra-hematologic toxicities as well as the need for supportive care observed in the AMI group were compared with ten myeloma patients treated in an identical protocol but without AMI. Hypotension was the most important adverse event of AMI infusion. No differences were observed in the time of engraftment between the AMI group and the control group neither was there any difference in the need for supportive care. Oral mucositis grade >2 was observed in 30% of the patients in both groups. Diarrhea grade >2 occurred only in two AMI patients but in five control patients. AMI preceding high-dose MEL is feasible, although adverse events are observed in some patients. Whether AMI could reduce the gastrointestinal toxicity associated with high-dose MEL can be reliably assessed only in prospective randomized trials.

Topics: Adult; Amifostine; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Feasibility Studies; Female; Graft Survival; Humans; Hypotension; Male; Melphalan; Middle Aged; Mouth Mucosa; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Pilot Projects; Stomatitis; Transplantation, Autologous

Severe systemic toxicity and hemodynamic changes after isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF-alpha) and melphalan, with or without interferon-gamma, have been reported in several series. We studied whether these side effects could be precluded by preventing leakage from the isolated circuit into the systemic circulation.. Clinical and pharmacokinetic data for 20 consecutive patients with recurrent melanoma of the limbs who were treated by ILP with TNF-alpha (3-4 mg) and melphalan, with or without interferon-gamma, were studied. Leakage rates and TNF-alpha levels were determined during and after ILP and were correlated with systemic toxicity and hemodynamic changes.. Only two patients experienced leaks (2% and 13%) during ILP. For 18 patients without leakage, the mean peak systemic TNF-alpha level was 2.8 ng/ml at 10 minutes after ILP. After leakage, the peak systemic TNF-alpha levels were 31.9 and 88.3 ng/ml at 5 minutes. Toxicity was mild and consisted mainly of fever (n = 17) and nausea/vomiting (n = 19) during the first day after ILP. Some patients developed tachycardia (n = 6), hypotension (n = 3; responding immediately to fluid challenge), a decrease in the WBC count (n = 3; grade I) or thrombocyte count (n = 11; grade I/II, no hemorrhage or therapeutic intervention), or hepatotoxicity [cytolysis (n = 15; 14 grade I/II and 1 grade IV) or hyperbilirubinemia (n = 7; grade I/II, all resolving spontaneously)]. Patients with tachycardia or hepatotoxicity exhibited significantly higher TNF-alpha levels after ILP, compared with other patients.. Systemic toxicity after ILP with TNF-alpha is minimal and does not differ from that after ILP with melphalan alone when leakage is adequately controlled.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Humans; Hypotension; Interferon-gamma; Leukopenia; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Tachycardia; Thrombocytopenia; Tumor Necrosis Factor-alpha

Percutaneous hepatic melphalan perfusion (PHMP) for the selective treatment of hepatic metastases is known to be associated with procedural hypotension and coagulation disorders. Studies on anesthetic management, perioperative course, complications, and postoperative recovery in the intensive care unit (ICU) have not been published.. In a retrospective observational study, we analyzed consecutive patients who were admitted for PHMP over a 6-year period (2016-2021). Analyses included demographic, treatment, and outcome data with regard to short-term complications until ICU discharge.. Fifty-three PHMP procedures of 16 patients were analyzed. In all of the cases, procedure-related hypotension required the median (range) highest noradrenaline infusion rate of 0.5 (0.17-2.1) μg kg min-1 and fluid resuscitation volume of 5 (3-14) liters. Eighty-four PHMP-related complications were observed in 33 cases (62%), of which 9 cases (27%) involved grade III and IV complications. Complications included airway constriction (requiring difficult airway management), vascular catheterization issues (which resulted in the premature termination of PHMP, as well as to the postponement of PHMP and to the performance of endovascular bleeding control after PHMP), and renal failure that required hemodialysis. Discharge from the ICU was possible after one day in most cases (n = 45; 85%); however, in 12 cases (23%), prolonged mechanical ventilation was required. There were no procedure-related fatalities.. PHMP is frequently associated with challenging cardiovascular conditions and complications that require profound anesthetic skills. For safety reasons, PHMP should only be performed in specialized centers that provide high-level hospital infrastructures and interdisciplinary expertise.

Topics: Adult; Aged; Aged, 80 and over; Catheterization, Peripheral; Female; Fluid Therapy; Hepatic Artery; Humans; Hypotension; Intensive Care Units; Liver; Liver Neoplasms; Male; Melphalan; Middle Aged; Norepinephrine; Perfusion; Respiration, Artificial; Retrospective Studies; Treatment Outcome

Isolated limb perfusion is the treatment of stage III melanoma with in-transit metastasis. This technique allows the administration of cytostatics at an effective concentration and temperature, which could not be administered systemically because of their toxicity. The toxicity due to leakage of the chemotherapy agent from the limb into the systemic circulation is the most serious short-term complication, and is manifested by a systemic inflammatory response syndrome in the immediate post-intervention period. Early detection of this complication and its peri-operative management requires a multidisciplinary approach, in which the anaesthesiologist plays a key role. A case of isolated lower limb perfusion is reported in which the procedure had to be interrupted due to the passage of tumour necrosis factor into the systemic circulation, with severe intra-operative haemodynamic repercussions.

Topics: Acid-Base Imbalance; Aged; Antineoplastic Combined Chemotherapy Protocols; Bicarbonates; Calcium; Chemotherapy, Cancer, Regional Perfusion; Epinephrine; Extravasation of Diagnostic and Therapeutic Materials; Female; Humans; Hyperthermia, Induced; Hypotension; Intraoperative Complications; Leg; Lymph Node Excision; Lymphatic Metastasis; Melanoma; Melphalan; Methylene Blue; Norepinephrine; Skin Neoplasms; Tachycardia; Tumor Necrosis Factor-alpha

Topics: Capillary Leak Syndrome; Combined Modality Therapy; Drug Therapy, Combination; Humans; Hypotension; Immunoglobulins, Intravenous; Immunosuppressive Agents; Intestinal Perforation; Male; Melphalan; Middle Aged; Monoclonal Gammopathy of Undetermined Significance; Prednisone; Sepsis; Sympathomimetics; Terbutaline; Theophylline

No established treatments for systemic AL amyloidosis have been determined, and only four reports have described allogeneic stem cell transplantation for this disease. We report the case of a patient with orthostatic hypotension, diarrhea, nephrotic syndrome, and cardiac amyloidosis due to systemic AL amyloidosis. Reduced intensity allogeneic stem cell transplantation (RIST) was performed using a conditioning regimen comprising fludarabine 125 mg/m2 and melphalan 90 mg/m2. Hematologically complete remission and symptomatic improvement were obtained without severe transplantation-related complications. RIST may thus offer a useful treatment strategy for systemic AL amyloidosis complicated by cardiac amyloidosis.

Topics: Adult; Amyloidosis; Diarrhea; Drug Therapy, Combination; Heart Diseases; Humans; Hypotension; Japan; Kidney Diseases; Male; Melphalan; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Remission Induction; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

In an attempt to limit toxicities associated with dose-intensive therapy used for transplant regimens, we performed a pilot study using amifostine with high-dose busulfan (12 mg/kg), melphalan (100 mg/m2), and thiotepa (500 mg/m2) in 21 patients with a variety of malignancies. After 3 days of oral busulfan, amifostine was given at 910 mg/m2 IV for 10 minutes, preceding the infusion of each of 2 doses of melphalan and thiotepa given for 4 days. Antiemetic premedication for amifostine was given to all patients. The median patient age was 50 years (range: 32-65 years). Twenty-one patients received 82 separate amifostine infusions. One patient discontinued amifostine after the second dose because of severe nausea and emesis, and two infusions were temporarily held secondary to hypotension. Of these 82 cycles, there was a total of 37 episodes of nausea/vomiting, 28 episodes of sneezing, 11 episodes of flushing, and 1 episode of oral paresthesia. Systolic blood pressure and mean arterial pressure decreased by a mean of 8.4 mm Hg and 5.0 mm Hg, respectively. In general, the infusion was well tolerated. Patients were observed until discharge home (N = 15), until initiation of an additional tandem transplant procedure (N = 4), or until death (N = 2). All twenty-one patients experienced nonhematologic toxicities grade II or greater. Grade II toxicities included mucositis (N = 21), gastrointestinal (N = 3), skin (N = 1), and liver (N = 1), and grade III toxicities included liver (N = 1). Mucositis was also scored according to a detailed toxicity assessment. Mucositis did not appear to be improved with amifostine when compared with a control group of patients not receiving amifostine. Renal dysfunction after transplantation was decreased in the amifostine group, whereas there was no significant effect on posttransplant hepatic dysfunction. Although these data demonstrate the feasibility of delivering parenteral amifostine in conjunction with dose-intensive chemotherapy and autologous peripheral blood stem cell transplantation, there was no evidence of a significant reduction in nonmarrow toxicities.

Topics: Adult; Aged; Amifostine; Antiemetics; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Blood Pressure; Busulfan; Feasibility Studies; Female; Flushing; Hematopoietic Stem Cell Transplantation; Humans; Hypotension; Male; Melphalan; Middle Aged; Mucous Membrane; Neoplasms; Pilot Projects; Protective Agents; Sneezing; Thiotepa; Transplantation, Autologous; Vomiting

Topics: Antineoplastic Combined Chemotherapy Protocols; Dextrans; Extremities; Humans; Hypotension; Interferons; Melphalan; Perfusion; Tumor Necrosis Factor-alpha

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Child; Extremities; Female; Hemorrhage; Humans; Hypotension; Leukopenia; Lymph Node Excision; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Melphalan; Methods; Middle Aged; Postoperative Complications; Sarcoma; Skin Neoplasms