Durable Responses to Thalidomide-Based Drug Therapy for Myelofibrosis With Myeloid Metaplasia

Mesa, Ruben A.; Elliott, Michelle A.; Schroeder, Georgene; Tefferi, Ayalew

doi:10.4065/79.7.883

Cited by 57 publications

(22 citation statements)

References 39 publications

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“…Recent updates on the long-term outcomes of patients in two thalidomide trials (alone or in combination with prednisone) 40,47 at the Mayo Clinic (Rochester, MN) have revealed that durable disease remission, even after the discontinuation of treatment, is achievable. 48 Twenty of 36 patients (56%) experienced some improvement in their clinical course (maximum rate of improvement, 77% [for patients with thrombocytopenia]). After a median follow-up of 25 months (range, 20 -56 months), 10 patients (28%) had ongoing responses.…”

Section: Novel Investigational Options For the Treatment Of Myelofibrmentioning

confidence: 99%

New approaches in the treatment of myelofibrosis

Hennessy¹,

Thomas²,

Giles³

et al. 2004

Cancer

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Myelofibrosis with myeloid metaplasia (MMM) is a chronic clonal neoangiogenesis disorder characterized by bone marrow fibrosis and neoangiogensis with extramedullary hematopoiesis. Identification of prognostic factors associated with MMM have not impacted the treatment of the disease, which continues to be palliative with the exception of allogeneic stem cell transplantation (SCT) for potential long-term disease-free survival in selected patients. Additional insights into the pathophysiology of MMM have resulted in the use of novel therapeutic strategies in the treatment of this disease. The rationale for the investigation of these agents in MMM and the status of clinical trials with various modalities such as angiogenesis inhibitors (e.g., thalidomide), tyrosine kinase inhibitors (e.g., imatinib mesylate), farnesyl transferase inhibitors (e.g., R115777), and other agents are reviewed, in addition to the potential roles of autologous and allogeneic SCT.

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Section: Novel Investigational Options For the Treatment Of Myelofibrmentioning

confidence: 99%

New approaches in the treatment of myelofibrosis

Hennessy¹,

Thomas²,

Giles³

et al. 2004

Cancer

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“…Thalidomide, especially when combined with prednisone, has been shown to result in significant response rates, particularly with respect to transfusion requirements and thrombocytopenia [10,20]. Initial experience with newer agents such as lenalidomide has demonstrated encouraging responses with respect to cytopenias and regression of splenomegaly.…”

Section: Conventional Therapymentioning

confidence: 97%

Allogeneic hematopoietic cell transplantation in myelofibrosis with myeloid metaplasia

Litzow¹,

Tefferi²

2007

Curr Hematol Malig Rep

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Myelofibrosis with myeloid metaplasia is a clonal disorder resulting from proliferation of aberrant hematopoietic progenitors. It can occur either de novo or secondary to an antecedent chronic myeloid disorder such as essential thrombocythemia or polycythemia vera. The only curative option is allogeneic hematopoietic cell trans-plantation, which can result in durable donor engraftment and regression of myelofibrosis in approximately 50% of eligible patients. Unfortunately the median age at presentation is 65 years and many patients have serious comorbidities, so the vast majority of patients are excluded from such an approach. Reduced-intensity conditioning regimens have been shown to result in successful engraftment and resolution of myelofibrosis with less toxicity, although follow-up remains relatively short. Complications such as graft-versus-host disease remain the major barrier to greater success. At present this modality is generally restricted to younger patients with intermediate-to high-risk disease. We provide a current algorithm for incorporating allogeneic transplantation into the management of patients with myelofibrosis. We are hopeful that recent advances in allogeneic transplantation, combined with progress in understanding the molecular pathobiology of chronic myeloproliferative disorders, will lead in the near future to a further refinement of prognostic determinants, new molecular targets to exploit, and therefore a dynamic evolution of the indications for allogeneic transplantation.

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“…15 Of the currently available drugs, those with demonstrated efficacy for alleviating anemia include Epo, 16 corticosteroids, 17 androgens, 18 danazol, 19 and thalidomide alone 20 or in combination with prednisone. 21 Response rates with these drugs generally have been meager, and accurate prediction of response has not been possible in most instances. The current results suggest that the presence of favorable cytogenetic abnormalities may predict response to Epo-based therapy independent of the serum Epo level, provided the levels are not too high (e.g., Ͻ 200 mU/mL).…”

Section: Discussionmentioning

confidence: 99%

Respective clustering of unfavorable and favorable cytogenetic clones in myelofibrosis with myeloid metaplasia with homozygosity for JAK2^V617F and response to erythropoietin therapy

Tefferi

Strand

Lasho

et al. 2006

Cancer

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BACKGROUNDPatients who have myelofibrosis with myeloid metaplasia (MMM) display recurrent, albeit nonspecific cytogenetic abnormalities that are diverse prognostically. For the current study, the authors explored the relation between specific cytogenetic clones and JAK2V617F mutational status in patients with MMM and the effects on treatment response to erythropoietin (Epo).METHODSConcomitantly collected blood granulocytes and bone marrow were processed for JAK2V617F mutation analysis and cytogenetic studies, respectively. Genomic DNA was amplified by polymerase chain reaction, and fluorescent dye chemistry sequencing was performed by using the same primers that were used for amplification.RESULTSAmong 105 study patients, cytogenetic abnormalities were detected in 47 patients (45%), and the JAK2V617F mutation was detected in 52 patients (50%). Comparison of mutational frequencies between favorable (normal, sole 13q−, or 20q− clones; n = 70 patients) and unfavorable (all other abnormalities; n = 35 patients) cytogenetic categories revealed a significantly different incidence of homozygous JAK2V617F between them (9% vs. 23%, respectively; P = .04). Furthermore, the mutant allele coexisted with several recurrent cytogenetic lesions. Among 25 patients who received Epo either alone (n = 17 patients) or in combination with hydroxyurea (n = 8 patients), 4 patients (16%) achieved a response, and none of them were homozygous for JAK2V617F. Conversely, a response was more likely (P = .0001) in the presence of favorable cytogenetic abnormalities (i.e., 3 of 4 responders carried sole 13q− or 20q− clones).CONCLUSIONSUnfavorable and favorable cytogenetic clones in MMM clustered with homozygosity for JAK2V617F and treatment response to Epo‐based therapy, respectively. Cancer 2006. © 2006 American Cancer Society.

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Durable Responses to Thalidomide-Based Drug Therapy for Myelofibrosis With Myeloid Metaplasia

Cited by 57 publications

References 39 publications

New approaches in the treatment of myelofibrosis

New approaches in the treatment of myelofibrosis

Allogeneic hematopoietic cell transplantation in myelofibrosis with myeloid metaplasia

Respective clustering of unfavorable and favorable cytogenetic clones in myelofibrosis with myeloid metaplasia with homozygosity for JAK2^V617F and response to erythropoietin therapy

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Durable Responses to Thalidomide-Based Drug Therapy for Myelofibrosis With Myeloid Metaplasia

Cited by 57 publications

References 39 publications

New approaches in the treatment of myelofibrosis

New approaches in the treatment of myelofibrosis

Allogeneic hematopoietic cell transplantation in myelofibrosis with myeloid metaplasia

Respective clustering of unfavorable and favorable cytogenetic clones in myelofibrosis with myeloid metaplasia with homozygosity for JAK2V617F and response to erythropoietin therapy

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Respective clustering of unfavorable and favorable cytogenetic clones in myelofibrosis with myeloid metaplasia with homozygosity for JAK2^V617F and response to erythropoietin therapy