melphalan and Hemorrhage

Topics: Antineoplastic Agents, Alkylating; Hemorrhage; Humans; Infant; Intravitreal Injections; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies

Topics: Bortezomib; Cyclophosphamide; Dexamethasone; Female; Hemorrhage; Humans; Immunoglobulin Light-chain Amyloidosis; Leiomyoma; Melphalan; Middle Aged

Although about 10 to 15% of patients with multiple myeloma (MM) develop AL amyloidosis, liver-restricted fatal amyloidosis is rare. We encountered such an MM patient. A 73-year-old female without a history of carpal tunnel syndrome was diagnosed with IgG-κ MM (Stage I by Durie & Salmon) in January, 2005. Because MM was exacerbated to Stage III in May, 2007, VAD (vincristine, adriamycin, dexamethasone) chemotherapy was performed with minor response, despite 3 courses of this regimen. Three courses of salvage chemotherapy (cyclophosphamide+melphalan; CM) were then performed with near partial response. In March, 2008, just before the 4th cycle of CM chemotherapy, she was slightly icteric with elevated biliary tract enzymes; therefore, treatment was switched to oral cyclophosphamide and prednisolone. At this time, she did not have macroglossia, skin eruption, gastrointestinal dysfunction, or bleeding. Echocardiography was also non-specific. One month later, she developed a marked bleeding tendency and leg edema. Laboratory tests showed a severe deterioration in liver function. In the middle of May, 2008, she progressed to hepatic coma and died of intracranial hemorrhage several days later. Autopsy showed that the liver was almost substituted by AL amyloid substance.

Topics: Aged; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Fatal Outcome; Female; Hemorrhage; Humans; Immunoglobulin Light-chain Amyloidosis; Liver Failure; Melphalan; Multiple Myeloma; Vincristine

Treatment-related mortality (TRM) is not uncommon in patients after the first course of vincristine-doxorubicin-dexamethasone (VAD) chemotherapy,but quite rare after melphalan-prednisolone (MP). This motivated us to compare the rates of TRM after the first course of VAD with those after the first course of MP. We retrospectively assessed survival and TRM in 179 patients treated for multiple myeloma with either MP or VAD. Survival was similar in two groups (P 50.463 in log-rank test). However, TRM was significantly higher inpatients after the first course of VAD (11 in 100 patients, 11.0%) than that after the first course of MP (1 in 79, 1.3%; P 5 0.010). Poor performance status (P 5 0.004) and advanced age (P 5 0.009) before treatment were independent significant factors associated with TRM after the first course of induction therapy. Pyogenic infection was the major cause of TRM after VAD (9 in 11, 81.8%). We concluded that VAD should be cautiously used as induction therapy in multiple myeloma patients, especially in elderly and/or those with poor performance status.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Doxorubicin; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Infections; Kidney; Kidney Diseases; Male; Melphalan; Multiple Myeloma; Neoplasm Staging; Prednisone; Retrospective Studies; Survival Analysis; Vincristine

Acquired loss of functional von Willebrand factor (VWF) has been termed the acquired von Willebrand syndrome (AVWS). AVWS is a rare adult-onset bleeding diathesis that is clinically similar to congenital von Willebrand disease (VWD), and occurs with a variety of autoimmune, lymphoproliferative, or myeloproliferative disorders. We have identified four patients with AVWS in association with immunoglobulin light chain (AL) amyloidosis. These patients, lacking any pre-existing or family history of abnormal bleeding, developed cutaneous, mucosal, or gastrointestinal bleeding in the course of their disease without deficiency of clotting factor X or other factors; the activated partial thromboplastin time (aPTT) was prolonged in three out of the four cases. Despite normal VWF antigen levels, VWF ristocetin cofactor activity (VWF:RCo) was low. Electrophoresis patterns of high molecular weight (HMW) VWF multimers were abnormal in two of the four cases. Two of the patients were treated with high-dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) and achieved hematologic remission. In these two patients, the bleeding diathesis improved and the coagulation parameters normalized, confirming a causal relationship between the plasma cell dyscrasia and the AVWS. AVWS should be considered in AL amyloidosis patients with hemorrhagic diatheses and normal clotting factor levels.

Topics: Adult; Amyloidosis; Antigens; Blood Protein Electrophoresis; Electrophoresis, Agar Gel; Hemorrhage; Humans; Immunoglobulin Light Chains; Male; Melphalan; Molecular Weight; Partial Thromboplastin Time; Peripheral Blood Stem Cell Transplantation; Remission Induction; Ristocetin; Transplantation, Autologous; von Willebrand Diseases; von Willebrand Factor

Patients with a central venous catheter (CVC) undergoing high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell transplantation (PBSCT) for malignancies are at high risk of thrombosis, but the use of anti-coagulant prophylaxis remains debatable in this setting of patients. We analyzed the efficacy and the safety of minidose warfarin in 228 patients in whom CVCs had been placed and who had received 292 HDC courses of therapy. The catheters remained in place for a mean of 173 (range 40-298) days. All patients received prophylactic oral warfarin in the fixed dose of 1 mg/day starting on the day of CVC insertion. Prophylaxis was interrupted during aplasia when platelet counts fell below 50,000/dL. There were no toxic deaths related to the prophylaxis. Overall there were 4 thrombotic events. Three occurrences were directly related to the catheter, while the remaining event was a deep saphenous-vein thrombosis. A number of potential predictive factors were analyzed for their impact on thrombotic events without finding any significant correlation. Four episodes of bleeding occurred, with each of these individuals having a normal INR but a platelet count below 50,000/dL. Minidose warfarin is effective and safe to use for preventing thrombotic events in this setting of patients.

Topics: Administration, Oral; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Catheterization, Central Venous; Cytarabine; Female; Hemorrhage; Humans; Male; Melphalan; Neoplasms; Peripheral Blood Stem Cell Transplantation; Platelet Count; Podophyllotoxin; Retrospective Studies; Risk Factors; Transplantation, Homologous; Venous Thrombosis; Warfarin

Acquired deficiency of factor X occurs in patients with systemic amyloid light-chain (AL) amyloidosis, presumably due to adsorption of factor X to amyloid fibrils. Of 368 consecutive patients with systemic AL amyloidosis evaluated at Boston Medical Center, 32 patients (8.7%) had factor X levels below 50% of normal. Eighteen of these patients (56%) had bleeding complications, which were more frequent and severe in the 12 patients below 25% of normal; 2 episodes were fatal. Ten factor X-deficient patients received high-dose melphalan chemotherapy followed by autologous stem cell transplantation. Of 7 patients alive 1 year after treatment, 4 had a complete hematologic response, and all 4 experienced improvement in their factor X levels. One of 2 additional patients with partial hematologic responses had improvement in factor X. Thus, aggressive treatment of the underlying plasma cell dyscrasia in AL amyloidosis can lead to the amelioration of amyloid-related factor X deficiency.

Topics: Amyloid; Amyloidosis; Antineoplastic Agents; Blood Coagulation Tests; Factor X Deficiency; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hemorrhage; Incidence; Melphalan; Transplantation, Autologous; Treatment Outcome

Lymphadenopathy associated with hemorrhage as a presenting feature of primary (AL) amyloidosis has not previously been described. We report two such cases one of whom had an acquired factor X and IX deficiency. The clinical presentations were characterized by sudden spontaneous enlargement of lymph nodes followed by partial regression. In both cases significant delay in diagnosis, and hence treatment, occurred due to the mode of presentation. One patient died with rapidly progressive disease but the other has had an excellent response to therapy with high-dose melphalan (HDM, 200 mg/m2) and peripheral blood stem cell rescue. AL amyloid should be considered in all patients presenting with hemorrhagic lymphadenopathy.

Topics: Adult; Amyloid; Amyloidosis; Diagnosis, Differential; Factor X Deficiency; Fatal Outcome; Hematopoietic Stem Cell Transplantation; Hemophilia B; Hemorrhage; Humans; Liver; Lymphatic Diseases; Male; Melphalan; Microscopy, Polarization; Middle Aged

We conducted a pilot study in 20 patients with high-risk or recurrent/refractory non-Hodgkin's lymphoma (NHL) using high-dose sequential chemotherapy (HDSC) and autologous hematopoietic cell transplantation (AHCT). After cytoreduction with standard salvage therapy, HDSC/AHCT was administered in 4 phases at 2- to 4-week intervals. Phase 1 consisted of cyclophosphamide 7 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) at 10 microg/kg per day and leukapheresis upon recovery from white blood cell nadir. The hematopoietic cell product was enriched by Percoll gradient separation and purged with a B-cell or T-cell monoclonal antibody panel and complement. Phase 2 consisted of methotrexate 8 g/m2 with leucovorin rescue and vincristine 1.4 mg/m2. Phase 3 was etoposide 2 g/m2 with G-CSF 5 microg/kg per day. In phase 4, the preparative regimen of mitoxantrone 60 mg/m2 and melphalan 180 mg/m2 was administered followed by AHCT. The NHL histologies were diffuse large cell, follicular/diffuse mixed, small noncleaved cell, T-cell-rich B-cell, lymphoblastic, and peripheral T cell. The remission status was first partial remission (PR1; n = 1) or beyond first complete remission (post-CR1; n = 19). Of the 20 patients enrolled, 11 proceeded through all 4 phases. Nine were removed from the study after the first or second phase because of progressive disease (n = 5), poor hematopoietic cell mobilization (n = 1), excessive toxicity (n = 2), and chronic active hepatitis C (n = 1). Treatment-related toxicities in the remaining 11 transplant recipients were cardiomyopathy, hemorrhagic cystitis, persistent cytopenias, acute renal failure, abnormal liver function test results, and infectious complications. There were no treatment-related deaths. Eight of the 11 transplant recipients were alive, 6 without disease, at a median follow-up of 2.7 years. The estimated median 2-year event-free survival was 55%, and overall survival was 70%. We conclude that HDSC/AHCT in refractory/recurrent NHL is associated with considerable acute and chronic toxicities. Given the toxicity profile, efficacy data were not sufficiently promising to warrant further study.

Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Purging; Cardiomyopathies; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Cyclophosphamide; Cystitis; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Infections; Leucovorin; Life Tables; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Mitoxantrone; Pilot Projects; Salvage Therapy; Survival Analysis; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine

Patients receiving high-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT) may experience life-threatening hemorrhagic myocarditis. The authors investigated whether HDC was associated with an acquired platelet defect. Platelet aggregation and release were evaluated after HDC in ten patients with either metastatic breast carcinoma or melanoma. Platelets underwent shape change and a primary wave of aggregation. High-dose chemotherapy was associated with the inhibition of secondary aggregation of platelets induced by adenosine diphosphate (ADP), arachidonic acid, prostaglandin H2 (PGH2) analog (U44619), and collagen. Although electron microscopic study of the platelets revealed normal morphologic features with an adequate number of dense bodies and alpha-granules, release of adenosine triphosphate (ATP) from dense granules was less than 20% of normal. The acquired platelet defect occurred before development of thrombocytopenia. Aggregation of platelets from normal volunteers was not inhibited by either the addition of the chemotherapeutic agents, chemotherapy metabolites, or the patients' sera. In conclusion, HDC induces an acquired abnormality in platelet secretion and aggregation which may contribute to the development of hemorrhagic complications after ABMT.

Topics: Adenosine Triphosphate; Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Platelet Disorders; Blood Platelets; Bone Marrow Transplantation; Breast Neoplasms; Carmustine; Cisplatin; Cyclophosphamide; Female; Hemorrhage; Humans; Male; Melanoma; Melphalan; Middle Aged; Myocarditis; Platelet Aggregation

Four basic coagulation tests, the prothrombin time, thrombin time, partial thromboplastin time, and prothrombin consumption time, were used, with relatively simple modifications, to demonstrate the presence of two circulating anticoagulants in the blood of a patient with IgG myeloma and a severe bleeding tendency.

Topics: Antithrombins; Blood Coagulation Tests; Ear Diseases; Factor IX; Factor V; Factor VIII; Hemagglutination Inhibition Tests; Hematoma; Hemorrhage; Hot Temperature; Humans; Immunoelectrophoresis; Immunoglobulin G; Male; Melphalan; Middle Aged; Multiple Myeloma; Plasmapheresis; Prednisone; Prothrombin Time; Thromboplastin

Topics: Adult; Aged; Blood Coagulation Tests; Bone Marrow Examination; Busulfan; Follow-Up Studies; Gastrointestinal Hemorrhage; Hemorrhage; Hepatomegaly; Humans; Male; Melphalan; Middle Aged; Oral Hemorrhage; Phosphorus Isotopes; Pipobroman; Polycythemia Vera; Splenomegaly; Thrombocythemia, Essential; Thrombosis; Tooth Extraction

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

Topics: Hematoma, Subdural; Hemorrhage; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Plasmapheresis