ABSTRACT
There are limited prospective data on lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVd) in transplant-eligible/transplant-ineligible patients with newly diagnosed multiple myeloma. Reliable biomarkers for efficacy and toxicity are required to better tailor therapy. Two parallel studies were conducted by Cancer Trials Ireland (CTI; NCT02219178) and the Dana-Farber Cancer Institute (DFCI; NCT02441686). Patients received four 21-day cycles of RsqVd and could then receive either another 4 cycles of RsqVd or undergo autologous stem cell transplant. Postinduction/posttransplant, patients received lenalidomide maintenance, with bortezomib included for high-risk patients. The primary endpoint was overall response rate (ORR) after 4 cycles of RsqVd. Eighty-eight patients were enrolled and 84 treated across the two studies; median age was 64.7 (CTI study) and 60.0 years (DFCI study), and 59% and 57% had stage II-III disease. Pooled ORR after 4 cycles in evaluable patients was 93.5%, including 48.1% complete or very good partial responses (CTI study: 91.9%, 59.5%; DFCI study: 95.0%, 37.5%), and in the all-treated population was 85.7% (44.0%). Patients received a median of 4 (CTI study) and 8 (DFCI study) RsqVd cycles; 60% and 31% of patients (CTI study) and 33% and 51% of patients (DFCI study) underwent transplant or received further RsqVd induction, respectively. The most common toxicity was peripheral neuropathy (pooled: 68%, 7% grade 3-4; CTI study: 57%, 7%; DFCI study: 79%, 7%). Proteomics analyses indicated elevated kallikrein-6 in good versus poor responders, decreased midkine in good responders, and elevated macrophage inflammatory protein 1-alpha in patients who stopped treatment from neurotoxicity, suggesting predictive biomarkers warranting further investigation.
Subject(s)
Multiple Myeloma , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bortezomib/adverse effects , Dexamethasone/adverse effects , Humans , Induction Chemotherapy , Lenalidomide/adverse effects , Middle Aged , Multiple Myeloma/therapy , Prospective StudiesSubject(s)
Antigens, Neoplasm/genetics , Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Myeloproliferative Disorders/drug therapy , Myeloproliferative Disorders/genetics , WT1 Proteins/genetics , Antimetabolites, Antineoplastic/pharmacology , Azacitidine/pharmacology , Humans , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/mortality , Prognosis , Treatment OutcomeSubject(s)
Rivaroxaban , Thromboxane A2 , Cerebellum , Conditioning, Classical , Platelet Activation , Platelet Aggregation , RewardSubject(s)
Myelodysplastic Syndromes/diagnosis , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease Management , Disease Susceptibility , Female , Humans , Male , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/etiology , Myelodysplastic Syndromes/mortality , Prognosis , Treatment OutcomeABSTRACT
Although transformation of the myeloproliferative neoplasms (MPNs) to acute myeloid leukemia (AML) is well documented, development of an MPN in patients previously treated for, and in remission from, AML is exceedingly rare. A case is described in which a patient was successfully treated for AML and in whom a JAK2 V617F-positive MPN was diagnosed after seven years in remission. Retrospective evaluation of the JAK2 V617F detected a low allele burden at AML diagnosis and following one course of induction chemotherapy. This putative chemoresistant clone subsequently expanded over the intervening seven years, resulting in a hematologically overt MPN. As AML relapse has not occurred, the MPN may have arose in a separate initiating cell from that of the AML. Alternatively, both malignancies possibly evolved from a common precursor defined by a predisposition mutation with divergent evolution into MPN through acquisition of the JAK2 V617F and AML through acquisition of different mutations. This case emphasizes the protracted time frame from acquisition of a disease-driving mutation to overt MPN and further underscores the clonal complexity in MPN evolution.
Subject(s)
Blast Crisis/drug therapy , Blast Crisis/genetics , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/drug therapy , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/genetics , Molecular Targeted Therapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Azacitidine/administration & dosage , DNA Mutational Analysis/methods , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Niacinamide/administration & dosage , Niacinamide/analogs & derivatives , Phenylurea Compounds/administration & dosage , SorafenibSubject(s)
Fusion Proteins, bcr-abl/genetics , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Pyrimidines/therapeutic use , Female , Fusion Proteins, bcr-abl/metabolism , Humans , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolismSubject(s)
Leptospirosis/diagnosis , Leptospirosis/pathology , Purpura, Thrombotic Thrombocytopenic/diagnosis , ADAM Proteins/genetics , ADAMTS13 Protein , Anti-Bacterial Agents/therapeutic use , Ceftriaxone/therapeutic use , Diagnosis, Differential , Humans , Leptospirosis/drug therapy , Leptospirosis/microbiology , Male , Middle AgedABSTRACT
While most patients with chronic myeloid leukemia (CML) express either e13a2 or e14a2 BCR-ABL1 transcripts, a significant minority expresses variant transcripts, of which e19a2 is the most common. Although considered to have a relatively favourable outcome, reported responses to tyrosine kinase inhibitor (TKI) therapy are variable with molecular monitoring in CML patients with e19a2 BCR-ABL1 transcripts rarely reported. A case of e19a2 BCR-ABL1 CML with marked thrombocytosis is described in which the value of molecular monitoring is emphasised during treatment interruptions, dose reductions, and changes. This case serves to demonstrate the requirement for prospective real-time quantitative PCR (RQ-PCR) assays for patients with variant BCR-ABL1 transcript types and standardisation of such assays to enable modern patient management.
ABSTRACT
Thalidomide has become an important agent in the treatment of myeloma. However, thalidomide induced erectile dysfunction is a serious complication which has received very little attention. In our hematology department, 6 out of 11 male patients developed erectile dysfunction (grade 3 in 5/6) within 4 weeks of starting thalidomide. Our results suggest that thalidomide induced impotence is a common complication in male hematology patients.
Subject(s)
Erectile Dysfunction/chemically induced , Multiple Myeloma/drug therapy , Thalidomide/adverse effects , Thalidomide/therapeutic use , Adult , Aged , Erectile Dysfunction/complications , Erectile Dysfunction/pathology , Humans , Male , Middle Aged , Multiple Myeloma/complicationsABSTRACT
We describe a case of blood transfusion-dependent myelodysplastic syndrome (refractory anaemia), associated with macrocytosis and elevated percentage of hypochromic cells. Following an acute hospital admission with a respiratory tract infection, the patient entered a complete and sustained remission.