melphalan and Thrombosis

Newly diagnosed multiple myeloma (NDMM) patients treated with immunomodulatory drugs are at high risk of venous thromboembolism (VTE), but data are lacking from large prospective cohorts. We present thrombosis outcome data from Myeloma IX (n = 1936) and Myeloma XI (n = 4358) phase 3 randomized controlled trials for NDMM that treated transplant-eligible and transplant-ineligible patients before and after publication of thrombosis prevention guidelines. In Myeloma IX, transplant-eligible patients randomly assigned to cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) induction had higher risk of VTE compared with patients treated with cyclophosphamide, thalidomide, and dexamethasone (CTD) (22.5% [n = 121 of 538] vs 16.1% [n = 89 of 554]; adjusted hazard ratio [aHR],1.46; 95% confidence interval [95% CI], 1.11-1.93). For transplant-ineligible patients, those randomly assigned to attenuated CTD (CTDa) induction had a higher risk of VTE compared with those treated with melphalan and prednisolone (MP) (16.0% [n = 68 of 425] vs 4.1% [n = 17 of 419]; aHR, 4.25; 95% CI, 2.50-7.20). In Myeloma XI, there was no difference in risk of VTE (12.2% [n = 124 of 1014] vs 13.2% [n = 133 of 1008]; aHR, 0.92; 95% CI, 0.72-1.18) or arterial thrombosis (1.2% [n = 12 of 1014] vs 1.5% [n = 15 of 1008]; aHR, 0.80; 95% CI, 0.37-1.70) between transplant-eligible pathways for patients treated with cyclophosphamide, lenalidomide, and dexamethasone (CRD) or CTD. For transplant-ineligible patients, there was no difference in VTEs between attenuated CRD (CRDa) and CTDa (10.4% [n = 95 of 916] vs 10.7% [n = 97 of 910]; aHR, 0.97; 95% CI, 0.73-1.29). However, arterial risk was higher with CRDa than with CTDa (3.1% [n = 28 of 916] vs 1.6% [n = 15 of 910]; aHR, 1.91; 95% CI, 1.02-3.57). Thrombotic events occurred almost entirely within 6 months of treatment initiation. Thrombosis was not associated with inferior progression-free survival (PFS) or overall survival (OS), apart from inferior OS for patients with arterial events (aHR, 1.53; 95% CI, 1.12-2.08) in Myeloma XI. The Myeloma XI trial protocol incorporated International Myeloma Working Group (IMWG) thrombosis prevention recommendations and compared with Myeloma IX, more patients received thromboprophylaxis (80.5% vs 22.3%) with lower rates of VTE for identical regimens (CTD, 13.2% vs 16.1%; CTDa, 10.7% vs 16.0%). However, thrombosis remained frequent in spite of IMWG-guided thromboprophylaxis, suggesting that new appro

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Incidence; Kaplan-Meier Estimate; Lenalidomide; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisolone; Progression-Free Survival; Risk Assessment; Thalidomide; Thrombophilia; Thrombosis; Transplantation, Autologous; Venous Thromboembolism; Vincristine

Topics: Aged; Autografts; Female; Hematopoietic Stem Cell Transplantation; Heparin; Humans; Male; Melphalan; Middle Aged; Thrombocytopenia; Thrombosis

A 39-year-old male presented with pedal edema, pleural effusion, splenomegaly, and generalized lymphadenopathy. Serum protein electrophoresis demonstrated the presence of a monoclonal protein. Histological examination of the spleen following splenectomy showed multifocal vascular proliferation and angiovascular lesions consistent with multicentric Castleman disease. He was treated with steroids and rituximab, but without improvement. The patient was found to have portal venous thrombosis and lower extremity arterial thrombosis. He then received combination chemotherapy with cyclophosphamide and mitoxantrone but developed a severe inflammatory polyneuropathy that left him disabled and wheelchair-bound. A diagnosis of multicentric Castleman disease with POEMS syndrome was made, and he then received high-dose chemotherapy with melphalan followed by autologous peripheral blood stem-cell transplantation. Following transplantation, his nerve conduction studies improved and his serum protein electrophoresis normalized. He is currently ambulatory and does not need wheelchair assistance. Hematopoietic stem-cell transplantation may be a treatment option for patients with multicentric Castleman disease and POEMS syndrome.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Castleman Disease; Guillain-Barre Syndrome; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Thrombosis; Transplantation, Autologous; Treatment Outcome

We report an adult autologous stem cell transplant (ASCT) patient who developed transplant-associated thrombotic microangiopathy (TMA) due to human herpesvirus-6 (HHV-6) reactivation. A 58-year-old female with Stage IIIA IgGkappa multiple myeloma received a melphalan (200 mg/m2) ASCT with discharge home after resolution of ASCT-related toxicities. She presented on D+20 with dyspnea, rash, and fever to 105 degrees F, followed by worsening dyspnea, hypotension, and capillary leak. Mental status (MS) changes were noted on D+23, but head CT and EEG were unremarkable. On D+29, a generalized seizure occurred with decline in platelet count and haptoglobin. TMA was noted on peripheral blood smear and therapeutic plasma exchange (TPE) was initiated on D+31. Lumbar puncture (LP) revealed CSF protein 74 mg/dL and white blood count 7,000/mm3 with 74% lymphocytosis. TPE was continued without improvement in her MS or thrombocytopenia despite improvement in microangiopathy. An MRI of the brain showed a left hippocampus abnormality, and an EEG was consistent with encephalopathy. Serum polymerase chain regimen (PCR) was negative for CMV, HSV1, and HSV2 but was strongly positive for HHV-6. Repeat LP protein was 597 mg/dL. Foscarnet was initiated, and cerebrospinal fluid (CSF) PCR for HHV-6 revealed 1,400 DNA copies/mL. Her MS greatly improved within 48 hr of antiviral therapy, serum HHV-6 became negative, and TPE was tapered without recurrence of her TMA. TMA with HHV-6 reactivation is likely an underdiagnosed entity. Given its fulminant course and favorable response to therapy, HHV-6 reactivation should be considered a potential etiology in patients with TMA after ASCT.

Topics: Antineoplastic Agents, Alkylating; Antiviral Agents; Combined Modality Therapy; Female; Herpesvirus 6, Human; Humans; Melphalan; Middle Aged; Multiple Myeloma; Roseolovirus Infections; Stem Cell Transplantation; Stroke; Thrombosis; Tissue Plasminogen Activator; Treatment Outcome; Virus Activation

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Catheterization, Central Venous; Catheters, Indwelling; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Mediastinal Neoplasms; Melphalan; Podophyllotoxin; Radiography; Thrombosis; Transplantation, Autologous

A 28-year-old women with idiopathic thrombocytosis was treated with melphalan before pregnancy, which resulted in a normal platelet count. During pregnancy 80 mg acetylsalicyclic acid was given daily to prevent microcirculatory thrombotic complications. Fetal outcome was normal.

Topics: Adult; Aspirin; Female; Humans; Melphalan; Pregnancy; Pregnancy Complications, Hematologic; Thrombocytosis; Thrombosis

178 episodes of essential thrombocytosis with symptoms of haemorrhage or thrombosis, were treated in 15 patients with melphalan (5 mg/m2 orally during 4 d). An average reduction in the platelet count of 77% was achieved by oral melphalan in 14 responding patients. 1 patient appeared to be refractory to oral therapy, but a decrease of the thrombocyte count was achieved after intravenous administration of melphalan. All responding patients experienced a relief of the thrombocytosis-associated clinical symptoms. Reduction of the thrombocyte count persisted for 3-4 wk.

Topics: Adolescent; Adult; Aged; Drug Administration Schedule; Female; Humans; Male; Melphalan; Middle Aged; Thrombocythemia, Essential; Thrombocytosis; Thrombosis

Topics: Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Follow-Up Studies; Humans; Male; Melanoma; Melphalan; Neoplasm Recurrence, Local; Neuritis; Oxygenators; Postoperative Complications; Surgical Wound Dehiscence; Surgical Wound Infection; Thrombosis; Tourniquets

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