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Population Pharmacokinetic Estimation of Melphalan Exposure Predicts Disease Control and Toxicity after Autologous Hematopoietic Cell Transplantation for Multiple Myeloma.

High-dose therapy (HDT) with melphalan followed by autologous hematopoietic cell transplantation (AHCT) remains standard for multiple myeloma (MM) consolidation. However, body surface area-based dosing results in interpatient variability in exposure, which may affect efficacy and toxicity. We retrospectively studied patients with MM who underwent AHCT and had serial melphalan concentrations measured after HDT. Melphalan area under the concentration-time curve (AUC) was calculated using non-compartmental analysis (NCA) and estimated using a two-compartment population pharmacokinetic (pop PK) mo…

Снижение дозы по сравнению со стандартными кондиционирования мелфалами для автоматической трансплантации стволовых клеток в множестве миеломы: ретроспективное исследование с одним центром.

Это ретроспективное одноцентральное исследование позволило оценить эффективность и безопасность сокращенного режима кондиционирования мелфала (см.140–180 мг/м2 для аутологической трансплантации стволовых клеток (ASCT) у пациентов с множественной миеломой (MM), не имеющих права на стандартную дозу (ASCT)200 мг/м2. Клинические результаты сравнивались между пациентами, получившими сокращенную дозу, и стандартными дозированными мелфаланами по сравнению с а five- годовой период с предварительным анализом подгрупп в зависимости от возраста и почечной функции. Результаты показали, что, несмотря на ме

Совпадение в аннотации оригинала
This retrospective, single‑center study evaluated the efficacy and safety of a reduced‑dose melphalan conditioning regimen (140–180 mg/m2) for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) ineligible for the standard dose (200 mg/m2). Clinical outcomes were compared between patients receiving reduced‑dose versus standard‑…

Несоответствие в оценке GFR для Melphalan Dosing в нескольких пациентах Myeloma, находящихся в автономном режиме: ретроспективный анализ.

Важнейшее значение для руководства дозированием онкологической терапии и сведения к минимуму рисков, связанных с токсичностью и недооценкой, имеет оценка ГФР. Роль цистатина С для оценки eGFR для дозирования мельфалана для нескольких пациентов миэломы, проходящих аутологическую трансплантацию стволовых клеток, недостаточно изучена. eGFR, основанный на сыворотке креатинина, может переоценить дозирование мелфалана, что приводит к токсичности в организме. one В five Пациенты, проходящие аутологическую трансплантацию стволовых клеток. В клинической практике сыворотка креатинин (sCr) используется д

Совпадение в аннотации оригинала
Key pointsAccurate GFR assessment is critical to guiding dosing of cancer therapy and minimizing the risks of toxicity and undertreatment. The role of cystatin C for estimating eGFR for melphalan dosing for multiple myeloma patients undergoing autologous stem cell transplant is poorly investigated. eGFR based on serum creatinine may overestimate melphalan do…

Доклад о деле: модификация пульсодоза пелфаланской терапии для клинической паллиэктальной плазматомы с предполагаемым распространением печени после хирургической эксцизии.

У старшего мальтийского пса был диагностирован одинокий ректальный экстрамеуллярный плазмоцитома, который был полностью акцизирован чистыми окраинами. 5 Месяцами позже были выявлены опухоли многофуакальной печени в плазменных клетках без признаков множественной миэломы. Системная химиотерапия была начата с использованием протокола пульсовой дозы в сочетании с преднизоном. В связи с периодическим ограничением доз миэлосоппрессией протокол лечения постепенно модифицировался путем сокращения продолжительности управления мелфаланом в рамках фиксированного цикла лечения. Модифицированный протокол б

Совпадение в аннотации оригинала
A senior male neutered Maltese dog was diagnosed with a solitary rectal extramedullary plasmacytoma that was completely excised with clean margins. 5 months later, multifocal hepatic plasma cell tumors were identified without evidence of multiple myeloma. Systemic chemotherapy was initiated using a pulse-dose melphalan protocol combined with prednisone. Due …

Treosulfan-Versus Melphalan-Based Reduced Intensity Conditioning in HLA-Haploidentical Transplantation for Patients ≥ 50 Years with Advanced MDS/AML.

Relapse and regimen-related toxicities remain major challenges in achieving long-term survival, particularly among older patients with high- … etting are limited. We retrospectively compared conditioning with fludarabine-cyclophosphamide (FC)-melphalan (110 mg/m2) and FC-treosulfan (30 g/m2) prior to HaploT using post-transplantation cyclophosphamide (PTCy) in patients with high-risk MDS/AML patients ≥ 50 years, transplanted from 2009-2021 at our institution (n = 80). After balancing patient chara …

Analysis of long-term mortality after total body irradiation-based and melphalan-based chemotherapy conditioning for acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for selected patients with acute myeloid leukemia. Yet, the influence of total body irradiation (TBI)-based conditioning as compared to non-TBI-based conditioning on long-term mortality is unclear. We retrospectively evaluated outcomes after TBI-based (n = 91) and non-TBI-based conditioning (melphalan-based, n = 248) for 1st allo-HSCT patients transplanted at the University Hospital Regensburg between 1999 and 2020. TBI was performed with an average dose rate of 4 cGy/min. Median follow-up was 8.3 yea…

A clickable melphalan for monitoring DNA interstrand crosslink accumulation and detecting ICL repair defects in Fanconi anemia patient cells.

Fanconi anemia (FA) is a genetic disorder associated with developmental defects, bone marrow failure and cancer. The FA pathway is crucial for the repair of DNA interstrand crosslinks (ICLs). In this study, we have developed and characterized a new tool to investigate ICL repair: a clickable version of the crosslinking agent melphalan which we name click-melphalan. Our results demonstrate that click-melphalan is as effective as its unmodified counterpart in generating ICLs and associated toxicity. The lesions induced by click-melphalan can be detected in cells by post-labelling with a fluoresc…

Comparison of reduced-toxicity conditioning protocols using fludarabine, melphalan combined with thiotepa or carmustine in allogeneic hematopoietic cell transplantation.

The age of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has increased during the last decades, mainly due to improved reduced-intensity/toxicity conditioning protocols. A reduced-intensity conditioning based on fludarabin, carmustin/BCNU and melphalan (FBM) has been previously developed at our institution. Since we observed detrimental effects in individual patients with compromised lung function, efforts have been made in order to replace BCNU by thiotepa (FTM) to reduce toxicity. In this study, we retrospectively analyzed the outcome, GvHD incidence, lung func…

Surgical versus percutaneous isolated pelvic perfusion (IPP) for advanced melanoma: comparison in terms of melphalan pharmacokinetic pelvic bio-availability.

BACKGROUND: Isolated pelvic perfusion (IPP) can be used to treat unresectable melanoma metastases of the pelvis. IPP can be performed either by surgical or percutaneous approaches, using different balloon catheters. The aim of this study was to examine whether the surgical and percutaneous approaches were comparable with respect to tumor drug exposure in the pelvis. METHODS: A pharmacokinetic study was performed in 5 melanoma patients treated with surgical IPP and five with percutaneous IPP. Both groups received melphalan at the dose of 30 mg/m2. Melphalan pharmacokinetic analyses were perfor…

Cardiac transplantation followed by dose-intensive melphalan and autologous stem-cell transplantation for light chain amyloidosis and heart failure.

BackgroundPatients with light chain (AL) amyloidosis who present with severe heart failure due to cardiac involvement rarely survive more than 6 months. Survival after cardiac transplantation is markedly reduced due to the progression of amyloidosis. Autologous stem-cell transplantation (ASCT) has become a common therapy for AL amyloidosis, but there is an exceedingly high treatment-related mortality in patients with heart failure.MethodsWe developed a treatment strategy of cardiac transplant followed by ASCT. Twenty-six patients were evaluated, and of 18 eligible patients, nine patients under

Radiopharmaceutical therapy of 5T33 murine myeloma by sequential treatment with samarium-153 ethylenediaminetetramethylene phosphonate, melphalan, and bone marrow transplantation.

BACKGROUND: Total-body irradiation, followed by hematopoietic system rescue by bone marrow transplantation (BMT), has been found to improve the response of patients with multiple myeloma to treatment with melphalan. The problems of nonhematopoietic toxicity from whole-body irradiation might be circumvented by using a bone-seeking radiopharmaceutical, such as samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP), to ablate the bone marrow. PURPOSE: A mouse model system for multiple myeloma was used to evaluate the potential therapeutic efficacy of sequential therapy with 153Sm-E…

Pyoderma gangraenosum (dermatitis ulcerosa) and monoclonal (IgA) globulin healed after melphalan treatment. Case report and review of the literature.

Since 1968 we have been treating a patient, who has had a combination of pyoderma gangraenosum (dermatitis ulcerosa) and signs that may indicate early multiple myeloma. She also had carcinoma of the colon, which was successfully operated. The pyoderma healed later after intensive and successful cytostatic treatment of the "myeloma". The ulcers remain practically healed and the protein pattern is normal in May 1977. Such cases are rare and a search in the literature has not been very rewarding. In our own series of more than 200 cases with myeloma this combination is unique. The lieterature is

Percutaneous hepatic perfusion with melphalan in liver metastatic uveal melanoma and viscoelastic hemostatic assays guided coagulation assessment for thrombocytopenia.

Thrombocytopenia is a well-documented hematologic consequence in patients undergoing percutaneous hepatic perfusion (PHP) to treat hepatic metastases secondary to ocular melanoma. In this case, four sequential PHP procedures resulted in significant thrombocytopenia, reaching 92, 75, 64, and 68% of baseline values. The thrombocytopenia was transient and spontaneously resolved within weeks. During the third procedure, a rotational thromboelastometry analysis was performed. We observed no clinically significant bleeding events, and rotational thromboelastometry analysis demonstrated a modest 11%

Cord blood transplantation with a reduced-intensity conditioning regimen using fludarabine and melphalan for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma with a poor prognosis when treated with chemotherapy alone; therefore, allogeneic stem cell transplantation is a consideration. We attempted cord blood transplantation (CBT) using a reduced-intensity conditioning regimen without total body irradiation (non-TBI-RIC) to allow for the best possible timing of transplantation and improve survival outcomes, particularly in older patients. Forty-eight patients (27 male, 21 female) underwent CBT using fludarabine (Flu) 125 mg/m2 and melphalan (Mel) 140 mg/m2 as pre-transplant condit…

Ice-cream used as cryotherapy during high-dose melphalan conditioning reduces oral mucositis after autologous hematopoietic stem cell transplantation.

Oral mucositis (OM) is one of the most frequent adverse events of high-dose conditioning chemotherapy with melphalan prior to autologous hematopoietic stem cell transplantation (AHSCT). It significantly reduces the patients' quality of life. One of the preventive strategies for OM is cryotherapy. We retrospectively analyzed whether commercially available ice-cream could prevent OM during the melphalan infusion. We retrospectively analyzed 74 patients after AHSCT to see whether there is any correlation between OM and cryotherapy (ice-cream), melphalan dose (140 mg/m2 or 200 mg/m2). The incidenc…

Tandem autologous hematopoietic cell transplantation with sequential use of total marrow irradiation and high-dose melphalan in multiple myeloma.

The goal of this phase II trial was to evaluate safety and efficacy of a tandem autologous hematopoietic cell transplantation (auto-HCT) using sequentially total marrow irradiation (TMI) at the dose of 12 Gy (4 Gy on days -3, -2, and -1) and melphalan 200 mg/m2 for patients with multiple myeloma (MM). TMI was performed using helical tomotherapy. Additional "boosts" (total 24 Gy) were applied for patients with active lesions as revealed by PET-FDG. Fifty patients with median age 58 years (41-64 years) were included and received tandem auto-HCT. TMI resulted in absolute neutropenia in all patien…

Sinusoidal obstruction syndrome/veno-occlusive disease after high-dose intravenous busulfan/melphalan conditioning therapy in high-risk Ewing Sarcoma.

This mono-institutional observational study was conducted to determine incidence, severity, risk factors, and outcome of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in high-risk Ewing sarcoma (ES) patients treated with intravenous busulfan and melphalan (BU-MEL) followed by autologous stem cell transplantation (ASCT). During the past 10 years, 75 consecutive ES patients resulted evaluable for the analysis. After diagnosis of SOS/VOD, defibrotide therapy was started as soon as the medication was available. The variables analyzed as potential risk factors were: gender, patie…

Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study.

Cytogenetic aberrations detected by interphase fluorescence in situ hybridization (iFISH) of plasma cells are routinely evaluated as prognostic markers in multiple myeloma. This long-term follow-up study aimed to assess the prognosis of systemic light chain amyloidosis (AL) patients treated with high-dose melphalan (HDM) chemotherapy and autologous stem cell transplantation, depending on iFISH results. Therefore, we analyzed a consecutive cohort of 123 AL patients recruited from 2003 to 2014. HDM was safe, with only 1 of 123 patients dying as a result of treatment-related mortality, and effect…