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Risk Factors for Acute Choroidal Ischemia after Intra-arterial Melphalan for Retinoblastoma: The Role of the Catheterization Approach.

PURPOSE: To identify risk factors for acute choroidal ischemia (ACI) after intra-arterial chemotherapy (IAC) for retinoblastoma. DESIGN: Re … dose, mean injection time, injection method (pulsatile vs. continuous), or concomitant intravitreal melphalan use. Treatment regimen (melphalan vs. combined melphalan plus topotecan; P < 0.05), catheterization route (internal carotid artery vs. external carotid or posterior communicating artery; P < 0.001), and catheterization type (occlusive into the ophth …

Thyroid hormone and insulin-like growth factor-I in patients with multiple myeloma treated with melphalan and prednisone.

BACKGROUND: The relationship between endocrine regulation and immune system has recently become the subject of intense investigations. The aim of this study was the comparative assessment of serum levels of selected hormones and insulin-like growth factor-I (IGF-I) in patients with multiple myeloma (MM) during applied therapy. METHODS: The levels of prolactin, hGH, TSH, fT3, fT4 and IGF-I in serum of 13 untreated patients with MM and in 16 healthy controls were determined. The patients were treated in cyclic courses with melphalan plus prednisone, and investigations were carried out in the fi…

Isolated limb perfusion with melphalan in the treatment of malignant melanoma of the extremities: a systematic review of randomised controlled trials.

Isolated limb perfusion is a surgical procedure for delivering a high dose of chemotherapeutic or immunochemotherapeutic agent to a localised area, thus avoiding the severity of side-effects caused by systemic administration. This technique is generally used for treatment of patients with tumours of the limbs and extremities. We have done a systematic review of randomised controlled trials assessing the effectiveness of this treatment in patients with melanoma of the extremities. Four trials of 1038 patients met our inclusion criteria and were analysed. Although our analysis confirmed the repo

[Assessment of regional and systemic toxicity of isolated hyperthermic extremity perfusion with tumor necrosis factor-alpha and melphalan].

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 p…

Prognostic factors and treatment of multiple myeloma: interest of a cyclic sequential chemohormonotherapy combining cyclophosphamide, melphalan, and prednisone.

1. A type 2 therapeutic trial consisting of the administration of monthly cycles of chemohormonotherapy, each cycle combining weekly sequenc … receiving continuous therapy with prednisone alone, prednisone + cyclophosphamide, or prednisone + melphalan. 2. Analysis of the main prognostic factors of the four trials indicates that a) IgG-type myelomas are associated with a better prognosis than IgA type; nonexcreting myelomas are associated with the best prognosis, while Bence Jones myelomas are ass …

Bortezomib-melphalan-prednisone versus lenalidomide-dexamethasone in elderly patients with multiple myeloma: the Real MM phase IV trial.

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… CI: confidence interval; ECOG PS: Eastern Cooperative Oncology Group Performance Status; HR: Hazard Ratio; IMWG: International Myeloma Working Group; ISS: International Staging System; Rd: lenalidomide-dexamethasone; VMP: bortezomib-melphalan-prednisone. … Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol. 2013;31(4):448-455. 4. Palumbo A, Bringhen S, Mateos M-V, et al. …

Long-term survival outcomes of allo-HCT in AML with fludarabine/melphalan conditioning and tacrolimus/sirolimus GVHD prophylaxis.

Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly offered as a consolidation strategy for older/infirm patients with acute myeloid leukemia (AML). Fludarabine/melphalan (Flu/Mel) conditioning is associated with effective disease control but results in significant toxicity and non-relapse mortality (NRM) when combined with calcineurin-inhibitors plus methotrexate or mycophenolate mofetil. Flu/Mel with alternative graft-versus-host disease (GVHD) prophylaxis may be better tolerated and result in superior outcomes in patients with AML. In this single-center retrospective an…

Percutaneous Hepatic Perfusion Melphalan Induced Sinusoidal Obstruction Syndrome (Veno-Occlusive Disease) in a Patient with Metastatic Uveal Melanoma.

INTRODUCTION: Percutaneous hepatic perfusion using the HEPZATO KIT™ (Delcath Systems, Inc., Queensbury, NY) is a US Food and Drug Administra … NCLUSION: To our knowledge, this represents the first case of sinusoidal obstruction syndrome after melphalan administration for percutaneous hepatic perfusion. Rapid progression of disease versus sinusoidal obstruction disease must be considered in patients who present with signs of liver injury/failure after this procedure as prompt diagnosis and treatmen …

Impact of melphalan day -1 vs day -2 on outcomes after autologous stem cell transplant for multiple myeloma.

BACKGROUND: Melphalan is the most common conditioning regimen used prior to autologous stem cell transplant (ASCT); however, there are varying data on optimal melphalan timing prior to transplant for best safety and efficacy. Historically, ASCT conditioning consisted of melphalan 200 mg/m2 on day 2 (D-2) (48 h prior to ASCT), but many institutions have since adopted a melphalan protocol with administration on day 1 (D-1) (24 h prior to SCT) or split dosing over the 2 days. The optimal timing of melphalan has yet to be determined. METHODS: In this single-center retrospective study, we analyzed…

Pars plana vitrectomy under melphalan irrigation for recurrent retinal detachment in eyes treated for retinoblastoma: a case report.

BACKGROUND: Tractional retinal detachment with or without secondary tear is a rare complication reported in less than 0.5% of in eyes treated for retinoblastoma. Pars plana vitrectomy (PPV) in eyes with history of retinoblastoma has been associated with a significant risk for recurrence, extraocular spread, and systemic metastases. We report here the successful management by PPV under melphalan irrigation of 2 children presenting with tractional retinal detachment after retinoblastoma therapy and scleral buckle surgery. CASE PRESENTATION: A 7-year-old girl with a history of bilateral retinobl…

Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma.

BackgroundMultiple myeloma is usually fatal due to serial relapses that become progressively refractory to therapy. CD19 is typically absent on the dominant multiple myeloma cell population but may be present on minor subsets with unique myeloma-propagating properties. To target myeloma-propagating cells, we clinically evaluated autologous T cells transduced with a chimeric antigen receptor (CAR) against CD19 (CTL019).MethodsSubjects received CTL019 following salvage high-dose melphalan and autologous stem cell transplantation (ASCT). All subjects had relapsed/refractory multiple myeloma and h…

Phase II trial of high-dose topotecan, melphalan and CY with autologous stem cell support for multiple myeloma.

In spite of high-dose chemotherapy followed by autologous hematopoietic SCT multiple myeloma (MM) eventually recurs, highlighting the need for more effective treatment approaches. Patients received topotecan 3.5 mg/m(2) intravenously on days -6 to -2, melphalan 70 mg/m(2) intravenously on days -3 and -2 and CY 1 g/m(2) intravenously on days -6, -5 and -4. Overall response rate (ORR) consisting of complete response and partial response (CR+PR, PFS, OS and toxicity are reported. Between August 2002 to March 2004, 60 patients (34 men and 26 women) with a median age of 61 years (range 45-72) were …

Oral mucositis and outcomes of autologous hematopoietic stem-cell transplantation following high-dose melphalan conditioning for multiple myeloma.

The purpose of this study was to assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes of autologous hematopoietic stem-cell transplantation (HSCT) following high-dose melphalan (Alkeran) conditioning in patients with multiple myeloma. A retrospective study of 115 consecutive autologous HSCT recipients with multiple myeloma who received high-dose melphalan conditioning before transplantation was undertaken at a single academic center. OM severity was assessed twice weekly using a validated scale beginning 3-4 days following conditioning and continuing u…

Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation.

In this prospective multicentre trial, 90 patients undergoing autologous stem cell transplantation (ASCT) were randomised to receive (n=43) or not receive (n=47) amifostine 910 mg/m(2) prior to melphalan 200 mg/m(2). Patients were monitored for regimen-related toxicity, engraftment, supportive care, response and survival. Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics, prior therapy and pre-ASCT disease responsiveness. Amifostine infusional side-effects were frequent, occurring in 65% of patients, but of mild severity. Amifostine …

Effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on al amyloidosis-associated renal disease.

BACKGROUND: Dose-intensive intravenous melphalan with autologous blood stem-cell transplantation induces remission of the plasma cell dyscrasia in a substantial proportion of patients with AL amyloidosis. The impact of this treatment on associated renal disease is not known. OBJECTIVE: To determine the effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on AL amyloidosis-associated renal disease. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENTS: 65 patients with AL amyloidosis and urinary protein excretion greater than 1…

High-dose melphalan and allogeneic peripheral blood stem cell transplantation for treatment of early relapse after allogeneic transplant.

Patients with acute leukemias relapsing within 1 year of an allogeneic BMT have a poor prognosis. We studied the use of melphalan 180 mg/m2 followed by allogeneic peripheral blood stem cells (PBSC) as salvage treatment for patients relapsing after related (n = 7) or matched unrelated transplants (n = 3). Diagnoses were AML (n = 4), ALL (n = 3), biphenotypic acute leukemia (n = 2) and CML in blast crisis (n = 1). Eight patients were beyond first relapse and none were in remission. The median time from previous transplant to relapse was 146 days (range 66-206). The melphalan dose was 90 mg/m2 in…

Tumor necrosis factor-alpha augments tumor effects in isolated hepatic perfusion with melphalan in a rat sarcoma model.

Isolated hepatic perfusion (IHP) is an attractive approach to treating nonresectable liver tumors, because the effects of systemic chemotherapy are poor and its application is hampered by severe general toxicity. In clinical and experimental settings, the efficacy of isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF alpha) in combination with melphalan to treat melanoma in transit and soft-tissue sarcoma has been well established. In an ILP model in rats, the authors previously observed synergistic anti-tumor effects of TNF and melphalan on BN 175 soft-tissue sarcoma extremit…

Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome.

The purpose of this study was to determine the incidence of veno-occlusive disease (VOD) after a high-dose regimen of busulfan, melphalan, and thiotepa and the risk factors for a more severe outcome. We followed 253 consecutive patients with malignant disorders who received autologous transplants after stem cell harvest followed by 12 mg/kg busulfan, 100 mg/m2 melphalan, and 500 mg/m2 thiotepa. Diagnosis of VOD was based on weight gain, hepatomegaly, and jaundice. Risk factors for moderate or severe VOD were identified using logistic regression models. VOD occurred in 70 of 253 patients (28%),…

High dose melphalan and total body irradiation with autologous marrow rescue in childhood acute lymphoblastic leukaemia after relapse.

High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3). Marrow was purged with Campath 1 in six children (four were children in CR3). All children had engraftment with a median of 30 days (range 18-70 days) to neutrophil count greater than 0.5 x 10(9)/l. Four children (16%) died from toxicity 1-4 months after autograft, two from pneumonitis, one from an intracere…