Scleromyxedema: role of high-dose melphalan with autologous stem cell transplantation

AbstractScleromyxedema, the most severe manifestation of the spectrum of lichen myxedematosus, is characterized by cutaneous mucinosis, extracutaneous manifestations, and a monoclonal gammopathy. Seven of 8 patients evaluated at our center were treated with high-dose melphalan (180 mg/m2 intravenously) and autologous peripheral blood stem cell transplantation, with marked improvement of gastrointestinal, central nervous system, pulmonary manifestations, and Karnofsky performance status. Five patients obtained a cutaneous complete remission and 2 patients had partial remissions. Three patients with slight progression in the skin at 12, 8, and 4 months after treatment received a second cycle of high-dose melphalan and had further symptomatic improvement. The lichen myxedematosus–scleromyxedema spectrum appears to be a continuum that requires the presence of a serum paraprotein and differs in severity of skin lesions, extracutaneous manifestations, and performance status. High-dose melphalan followed by autologous transplantation appears effective for improving the symptoms and systemic manifestations of scleromyxedema.

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The impact of pulmonary function in patients undergoing autologous stem cell transplantation

Blood Advances ◽

10.1182/bloodadvances.2021004863 ◽

2021 ◽

Author(s):

Jesus Duque-Afonso ◽

Sophie Ewald ◽

Gabriele Ihorst ◽

Miguel Waterhouse ◽

Tim Strüessmann ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Karnofsky Performance Status ◽

Performance Status ◽

High Dose ◽

Toxic Substances ◽

Hematopoietic Stem ◽

High Dose Melphalan ◽

The Impact

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is an established therapy for patients with hematological malignancies. The age of patients undergoing auto-HSCT, and therefore the co-morbidities, has increased during the last decades. However, the assessment of organ dysfunction prior auto-HSCT has not been well undertaken. Therefore, we analyzed retrospectively the association of clinical factors, lung and cardiac function with outcome and complications after conditioning with BEAM (BCNU/carmustin, etoposide, cytarabine, melphalan) and high-dose melphalan of patients undergoing auto-HSCT. In this study, we included 629 patients treated with auto-HSCT (334 conditioned with BEAM and 295 with high-dose melphalan) at our institution between 2007 and 2017. The median follow-up for patients conditioned with BEAM was 52 months (range:0.2-152) and with high-dose melphalan 50 months (range:0.5-149). In the multivariate analysis, we identified progressive disease, CO-diffusion capacity corrected for hemoglobin (DLCOcSB)<60% of predicted, Karnofsky performance status (KPS)≤80%, HCT-CI score≥4 and age>70 years to be associated with decreased overall survival (OS) in patients treated with BEAM. Similarly, DLCOcSB<60% of predicted, HCT-CI score ≥4 and age>60 years were identified in patients treated with high-dose melphalan. Abnormalities in DLCOcSB<60% of predicted were associated with chemotherapy with lung toxic substances, mediastinal radiotherapy, KPS≤80%, current/previous smoking and treatment at the intensive care unit. Patients with decreased DLCOcSB<60% of predicted had more frequently non-relapse mortality, including pulmonary cause of death. In summary, we have identified DLCOcSB<60% of predicted as an independent risk factor associated with decreased OS in patients conditioned with BEAM and high-dose melphalan prior auto-HSCT.

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The Effects of Induction Chemotherapy and High-Dose Melphalan with Tandem Autologous Transplantation in Multiple Myeloma: The Prospective Randomized DSMM 2 Study.

Blood ◽

10.1182/blood.v110.11.446.446 ◽

2007 ◽

Vol 110 (11) ◽

pp. 446-446 ◽

Cited By ~ 1

Author(s):

Christian Straka ◽

Peter Liebisch ◽

Burkhard Hennemann ◽

Bernd Metzner ◽

Hans Salwender ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Induction Chemotherapy ◽

Autologous Transplantation ◽

High Dose ◽

Significant Difference ◽

High Dose Melphalan

Abstract The concept of the DSMM 2 study was to give age-adjusted high-dose treatment to elderly myeloma patients in order to balance efficacy and toxicity. The value of conventional induction chemotherapy before high-dose melphalan and autologous stem cell transplantation and the durability of unmaintaned remissions afterwards was addressed. Between September 2001 and September 2006, 434 multiple myeloma patients 60–70 years of age with 0–1 cycle of pretreatment were recruited from 45 centers. The median age was 65 years. The patients were randomized to receive 4 cycles of conventional induction chemotherapy [A1] (n=216; VAD or idarubicin/Dex in 88%) or no induction chemotherapy [A2] (n=218). Instead of induction chemotherapy, patients in [A2] received only one short course of dexamethasone 40 mg orally (days 1–4 and 8–11). Subsequently, stem cells were mobilized after combination chemotherapy with ifosfamide, epirubicin and etoposide (IEV) followed by G-CSF; stem cells could be collected in 97% of the patients. Then the patients proceeded to tandem MEL140 (melphalan 140 mg/m2) and autologous peripheral blood stem cell transplantation with a time interval between high-dose cycles of 2 months. No consolidation or maintenance treatment was scheduled. Analyses were performed in an intent-to-treat approach. 87% of patients completed the first transplant, 74% the second. Overall, the treatment was well tolerated and grade 3/4 infections and stomatitis after high-dose melphalan occurred in 37% and 9% of patients, respectively. The overall mortality (tumor and/or toxicity) during treatment was 7.1%: 4.5% during the induction phase (6.1% in [A1] versus 2.9% in [A2]), 1.5% after mobilization and 1.1% after high-dose therapy. Notably, the best response (EBMT criteria) at the end of treatment in patients randomized to [A1] (16% CR, 64% PR) or [A2] (18% CR, 69% PR) was not different. An early loss of tumor control with disease progression occurred in 6% in [A1] versus 1% in [A2]. With a median follow-up time of 20 months, there was no significant difference in the median event-free survival (EFS) (22 months in [A1] versus 20 months in [A2]) and not in the overall survival (OS) at 4 years (63% in [A1] versus 65% in [A2]). In ≥ 50% of patients, the time between last treatment and progression was > 16 months. The EFS of patients 60–64 years of age and 65–70 years of age was the same. In conclusion, there was no benefit of conventional induction chemotherapy with VAD- or VAD-like regimens in patients receiving tandem MEL140 with autologous transplantation. This induction treatment therefore may be avoided. Tandem-MEL140 is feasible and well tolerated in the majority of elderly patients with symptomatic myeloma. Its profound and durable anti-tumor effect was demonstrated by prolonged unmaintained remissions. The addition of new agents given as consolidation or maintenance probably will further improve treatment results.

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