melphalan and Rhabdomyolysis

Following isolated limb perfusion (ILP) with TNF alpha and melphalan the damage to muscle tissue and its systemic consequences in terms of myoglobinemia and myoglobinuria as well as the activation of the cytokine cascade were investigated. We measured the compartmental pressure of the limb during and after perfusion and determined the serum changes of myoglobin, creatine kinase (CK), interleukin (IL)-6, IL-1, s-IL-2-receptor, TNF-receptor, and ICAM-1 levels. The compartmental pressure rose significantly during ILP and decreased after reperfusion. Following its course, the decision whether to perform a fasciotomy or not can be more reliably made. Serum myoglobin levels exceeded 200 times normal values and the increase occurred significantly earlier than that of CK, thus enabling judgement of the risk of renal failure (crush kidney syndrome). The elevation of serum IL-1 and IL-6 values correlated with the frequency of cardiopulmonary problems (hyperdynamic shock) and facilitated counter-maneuvers. Our data, although obtained from ILP with TNF alpha, could be used to monitor toxicity also when other drug regimens are administered.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Compartment Syndromes; Cytokines; Extremities; Female; Follow-Up Studies; Humans; Hyperthermia, Induced; Male; Melanoma; Melphalan; Middle Aged; Myoglobin; Myoglobinuria; Neoplasm Recurrence, Local; Recombinant Proteins; Rhabdomyolysis; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

Topics: Amines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Boronic Acids; Bortezomib; Combined Modality Therapy; Creatine Kinase, MM Form; Cyclohexanecarboxylic Acids; Dexamethasone; Drug Synergism; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Immunologic Factors; Kidney Diseases; Lenalidomide; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Polyneuropathies; Pravastatin; Pyrazines; Rhabdomyolysis; Thalidomide

At age of 57 years, a man experienced an episode of rhabdomyolysis. On that occasion muscle biopsy was not performed, however monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. Further he developed a moderate proximal muscle weakness with CK level persistently elevated (1000-1200U/l). When he came to our observation, at age 67, a muscle biopsy revealed an amyloid myopathy and multiple myeloma was at the same time disclosed. Terminal complement complex C5b9 (membrane attack complex) deposits were found in the vessel walls and muscle fibers surface depicted by amyloid. Our case suggests to keep in mind the possibility that amyloid myopathy may begin as an isolate episode of rhabdomyolysis. The detection of complement complex C5b9 suggests that complement cascade is implicated in the muscular damage of amyloid myopathy.

Topics: Aged; Amyloidosis; Betamethasone; Biopsy; Blood Vessels; Complement Membrane Attack Complex; Complement System Proteins; Creatine Kinase; Glucocorticoids; Humans; Male; Melphalan; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Myeloablative Agonists; Rhabdomyolysis; Treatment Outcome

Severe limb toxicity following isolated limb perfusion (ILP) can lead to compartmental compression syndrome and severe rhabdomyolysis, occasionally necessitating amputation of the affected limb. We determined whether laboratory tests for muscle damage and inflammation could predict impending limb toxicity.. All 184 consecutive ILPs performed in our institute from 1988 to 1994 were included in this study. Creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and white blood cell (WBC) counts were determined on post-ILP days 1-4, 6, 8, and 15.. "Late peak" CK patterns, characterised by a peak on or after the 5th post-perfusion day, were strongly associated with severe limb toxicity (p < 0.001). Severe toxicity did develop in 40% of the limbs when CK values exceeded 1000 IU/L on the 2nd to 5th post-ILP day (p < 0.001). There was a correlation between the peak CK and the individual grades of toxicity (r = 0.6, p < 0.001). Serum LDH and ASAT values peaked 2.9 and 3.4 days after the CK peak respectively. Severe limb toxicity was statistically significantly associated with higher WBC counts from the 2nd post-ILP day onwards.. CK values exceeding 1000 IU/L after the 1st and WBC counts increasing after the 2nd post-ILP day could be predictors of impending limb toxicity. These patients should be observed closely for signs of compartmental compression syndrome and severe rhabdomyolysis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Aspartate Aminotransferases; Biomarkers; Chemotherapy, Cancer, Regional Perfusion; Compartment Syndromes; Creatine Kinase; Drug Monitoring; Extremities; Female; Humans; Interferon-gamma; L-Lactate Dehydrogenase; Leukocyte Count; Linear Models; Male; Melanoma; Melphalan; Middle Aged; Predictive Value of Tests; Rhabdomyolysis; Sarcoma; Toxicity Tests; Tumor Necrosis Factor-alpha

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Combined Modality Therapy; Dacarbazine; Dactinomycin; Evaluation Studies as Topic; Extremities; Humans; Hyperthermia, Induced; Incidence; Melanoma; Melphalan; Neoplasm Metastasis; Osteosarcoma; Rhabdomyolysis; Skin Neoplasms; Treatment Outcome