In patients 65 or younger with multiple myeloma, high-dose consolidation therapy was associated with longer survival and more myelotoxicity than conventional-dose therapy. Lenalidomide maintenance ...improved progression-free survival but not overall survival.
High-dose chemotherapy plus autologous stem-cell transplantation, as compared with conventional chemotherapy, prolongs progression-free survival and overall survival among patients with newly diagnosed multiple myeloma.
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and it is currently the standard of care for patients who are younger than 65 years of age. However, since autologous stem-cell transplantation has substantial toxic effects and requires prolonged hospitalization, the comparison with less toxic, orally administered treatments is important. Immunomodulatory drugs and proteasome inhibitors have significantly improved outcomes in patients, regardless of whether they are eligible for transplantation.
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These improvements have raised questions about the role of transplantation in comparison with conventional . . .
Recent developments have led to remarkable improvements in the assessment and treatment of patients with multiple myeloma (MM). New technologies have become available to precisely evaluate the ...biology and extent of the disease, including information about cytogenetics and genetic abnormalities, extramedullary manifestations and minimal residual disease. New, more effective drugs have been introduced into clinical practice, which enable clinicians to significantly improve the outcome of patients but also pose new challenges for the prevention and management of their specific side effects. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of patients, as access to the most sophisticated advances may vary depending on local circumstances. Here, we propose the minimal requirements and possible options for diagnosis, monitoring and treatment of patients with multiple myeloma.
BACKGROUND Storing ovarian tissue for fertility preservation in cancer patients carries the risk of the presence of malignant cells that could lead to recurrence of cancer after reimplantation. ...Methods to exclude presence of cancer cells were used to improve the safety of cryopreservation–reimplantation procedures. METHODS Fifty-eight patients with hematological malignancies were referred for the storage of ovarian tissue for fertility preservation. Investigation included preoperative imaging and histological evaluation of fresh ovarian tissue. After thawing markers to detect minimal residual disease (MRD) were used and compared with patient's disease used as positive control (five patients). RESULTS Preoperative imaging detected disease in the ovaries (two patients). Conventional histology post-tissue harvesting did not disclose malignant cells (56 patients). MRD results post-thawing were negative in Hodgkin's disease (CD30 immunohistochemical staining), in T- and B-cell lymphoma (PCR for T-cell receptor and Ig clones, respectively) and in two chronic myelogenous leukemia patients (RT–PCR for BCR–ABL gene expression). However, highly sensitive real-time RT–PCR was positive in one CML patient and, this alarming result avoided tissue transplantation. CONCLUSIONS Preoperative imaging prevented operations and storage of tissue with cancer. Evaluation of stored ovarian tissue for MRD using sensitive markers is essential to increase safety and to prevent reimplantation of tissue with malignant cells.
From Istituto di Ematologia, Università Cattolica S. Cuore, Rome, Italy (GP, LP, MTV); Department of Hematology, Hadassah University Hospital, Jerusalem, Israel (DB-Y)
Correspondence: Giuseppe Leone, ...Istituto di Ematologia, Universita Cattolica S. Cuore, L. go A. Gemelli, 1, 00168 Rome, Italy. E-mail: gleone{at}rm.unicatt.it
Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is an increasingly recognized treatment complication in patients treated with radiotherapy or chemotherapy for previous hematologic malignancies or solid tumors. Distinct clinical entities have been described according to the primary treatment, corresponding to defined genetic lesions. Chromosome 7 and/or 5 losses or deletions are typical of alkylating agent-induced AML, while development of t-AML with balanced translocations involving chromosome bands 11q23 and 21q22 has been related to previous therapy with drugs targeting DNA-topoisomerase II. In addition, antimetabolites, and in particular the immunosuppressant azathioprine, have been shown to induce defective DNA-mismatch repair. This could promote survival of misrepaired cells giving rise to the leukemic clone. Individual predisposing factors, including polymorphisms in detoxification and DNA repair enzymes have been identified. Their combination may significantly increase the risk of t-MDS/AML. Among patients with hematologic malignancies, long-term survivors of Hodgkins lymphoma are exposed to an increased risk of t-MDS/AML, particularly when receiving MOPP-based, and escalated BEACOPP regimens, and when alkylators are combined with radiotherapy. Patients with Hodgkins and non-Hodgkins lymphoma are at highest risk when total body irradiation followed by autologous stem cell transplantation is used as rescue or consolidation therapy. The addition of granulocyte-colony-stimulating factor and radiotherapy plays a significant role in t-AML following treatment of children with acute lymphoblastic leukemia. In non-hematologic malignancies, treatment for breast cancer and germ-cell tumors has been associated with a 1–5% lifetime risk of both lymphoid as well as myeloid leukemia. In all cases the risk of t-MDS/AML drops sharply by 10 years after treatment.
Key words: susceptibility, therapy-related, AML, MDS.
Renal impairment is associated with poor prognosis in multiple myeloma (MM). This subgroup analysis of the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of ...bortezomib vs high-dose dexamethasone assessed efficacy and safety in patients with relapsed MM with varying degrees of renal impairment (creatinine clearance (CrCl) <30, 30-50, 51-80 and >80 ml min(-1)). Time to progression (TTP), overall survival (OS) and safety were compared between subgroups with CrCl < or =50 ml min(-1) (severe-to-moderate) and >50 ml min(-1) (no/mild impairment). Response rates with bortezomib were similar (36-47%) and time to response rapid (0.7-1.6 months) across subgroups. Although the trend was toward shorter TTP/OS in bortezomib patients with severe-to-moderate vs no/mild impairment, differences were not significant. OS was significantly shorter in dexamethasone patients with CrCl < or =50 vs >50 ml min(-1) (P=0.003), indicating that bortezomib is more effective than dexamethasone in overcoming the detrimental effect of renal impairment. Safety profile of bortezomib was comparable between subgroups. With dexamethasone, grade 3/4 adverse events (AEs), serious AEs and discontinuations for AEs were significantly elevated in patients with CrCl < or =50 vs >50 ml min(-1). These results indicate that bortezomib is active and well tolerated in patients with relapsed MM with varying degrees of renal insufficiency. Efficacy/safety were not substantially affected by severe-to-moderate vs no/mild impairment.
Objectives: Major risk factors of oral squamous cell carcinoma (OSCC) are environmental and can lead to DNA mutagenesis. Mismatch repair (MMR) system functions to repair small DNA lesions, which can ...be targeted for promoter hypermethylation. We therefore wanted to test whether hypermethylation of MMR genes (hMLH1, hMSH2) could contribute to oral carcinogenesis by correlating the information to patient clinical data.
Methods: Genomic DNA was extracted from 28 OSCC and six normal oral epithelium samples. The methylation status of the two MMR genes was assessed using Methylation Specific PCR after DNA modification with sodium bisulfite. Serial sections of the same tissues were immunostained with antibodies against hMLH1 and hMSH2 protein.
Results: Promoter hypermethylation was observed in 14/28 OSCC cases. Remarkably, 100% of patients with multiple oral malignancies showed hypermethylation in hMLH1 or hMSH2 compared with 31.5% of single tumor patients. In 10 cancer cases, expression of the hMLH1 and hMSH2 genes by immunostaining showed reduced or absence of expression of one of the genes, although some did not reflect the methylation status.
Conclusions: Hypermethylation of hMLH1 and hMSH2 might play a role in oral carcinogenesis and may be correlated with a tendency to develop multiple oral malignancies.
•Morel Lavallée Lesion is an elusive diagnosis & can cause a life-threatening state.•Diagnosis of Morel Lavallée Lesion is clinical, but aided by several modalities.•There are several treatment ...options for Morel Lavallée Lesion.•Morel Lavallée Lesion should be treated when diagnosed.
Morel-Lavallée lesion (MLL) is an uncommon entity, by which shearing forces result in a closed degloving lesion. This can result in an infected hematoma and lead to a life-threatening situation.
We present a case of a 59-year-old patient who presented to our emergency department. This patient had a crushing injury, and later was found to have an infected MLL. The patient was treated with surgical drainage, and 2 split thickness skin grafts. The patient fully healed.
We review the current literature regarding MLL and diagnostic tools in order to accurately and rapidly diagnose this often-missed entity. Special emphasis is given to the treatment of MLL, with the current knowledge as reflected in the literature.
It is important for caregivers to know the diagnostic steps and pitfalls of this elusive diagnosis in order to diagnose and treat MLL quickly, before it turns into a life-threatening state for the patient.
The addition of daratumumab to lenalidomide and dexamethasone resulted in superior response rate and progression-free survival, as compared with lenalidomide and dexamethasone alone, at a cost of ...more frequent neutropenia and infusion reactions.
The incorporation of proteasome inhibitors and immunomodulatory drugs into the standard of care has improved outcomes in patients with multiple myeloma over the past 10 years,
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but most patients still eventually have a relapse.
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Relapse can occur even after standard complete remission in the context of first-line therapy, and studies are therefore evaluating deeper responses in a category termed “minimal residual disease–negative” (i.e., results below the threshold for minimal residual disease) that is prognostic with regard to a rate of disease progression in a time-to-event analysis and overall survival.
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However, this category of minimal residual disease status has . . .