Therapy of Early Stage Myelodysplastic Syndrome (MDS) with Anti-Thymocyte Globulin (ATG) and Etanercept.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1462-1462
Author(s):  
Bart L. Scott ◽  
Aaron L. Holsinger ◽  
Aaravind Ramakrishnan ◽  
Barry Storer ◽  
Pamela S. Becker ◽  
...  
Keyword(s):  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Red Blood Cell ◽  
Early Stage ◽  
Pilot Trial ◽  
Risk Groups ◽  
Red Blood Cell Transfusion ◽  
Transfusion Independence ◽  
Phase 2 Trial ◽  
Soluble Tnf Receptor

Abstract Immunosuppressive therapies have proven valuable in treating ineffective hematopoiesis in patients with Myelodysplastic Syndrome (MDS). Following an encouraging pilot trial, we evaluated the combination of equine anti-thymocyte globulin (ATGAM) and the soluble TNF receptor etanercept in a phase 2 trial. So far 23 patients with MDS (6-RA, 4-RARS, 12-RCMD, 1-RAEB-1) in IPSS risk groups low (n=8) or intermediate-1 (n=15) have been enrolled. All patients were platelet or red blood cell transfusion dependent. Nineteen patients completed therapy with I.V. ATGAM at 40mg/kg/day for four consecutive days, followed by etanercept, 25mg s.c. twice a week for 2 weeks every month for 4 months. The regimen was well tolerated and the majority of adverse events were anticipated infusional reactions related to ATGAM administration. Responses were assessed by modified International Working Group criteria. Twelve patients had hematological improvement (HI)-erythroid, 2 HI-neutrophil, and 3 HI-platelet. Five patients achieved red blood cell and one patient platelet transfusion independence. There was one complete remission in a patient with a co-existing diagnosis of multiple sclerosis. Thus, the overall response rate by intent to treat analysis among the 23 patients was 61%. Four patients did not complete their first course of therapy due to anaphylactic reaction, thrombosis of a pre-existing femoral graft, myocardial infarction, and patient preference. Among patients who completed treatment 74% had a hematological response, with duration of at least 5 months. Combination therapy with ATG and etanercept was active and safe in unselected patients with low and intermediate-1 risk MDS.

scholarly journals Durable Red Blood Cell Transfusion Independence in a Patient with an MDS/MPN Overlap Syndrome Following Discontinuation of Iron Chelation Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Harpreet Kochhar ◽  
Chantal S. Leger ◽  
Heather A. Leitch
Keyword(s):  
Blood Cell ◽  
Iron Overload ◽  
Red Blood Cell ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Red Blood Cell Transfusion ◽  
Favorable Effect ◽  
Iron Chelation Therapy ◽  
Transfusion Independence ◽  
Rbc Transfusion

Background. Hematologic improvement (HI) occurs in some patients with acquired anemias and transfusional iron overload receiving iron chelation therapy (ICT) but there is little information on transfusion status after stopping chelation.Case Report. A patient with low IPSS risk RARS-T evolved to myelofibrosis developed a regular red blood cell (RBC) transfusion requirement. There was no response to a six-month course of study medication or to erythropoietin for three months. At 27 months of transfusion dependence, she started deferasirox and within 6 weeks became RBC transfusion independent, with the hemoglobin normalizing by 10 weeks of chelation. After 12 months of chelation, deferasirox was stopped; she remains RBC transfusion independent with a normal hemoglobin 17 months later. We report the patient’s course in detail and review the literature on HI with chelation.Discussion. There are reports of transfusion independence with ICT, but that transfusion independence may be sustained long term after stopping chelation deserves emphasis. This observation suggests that reduction of iron overload may have a lasting favorable effect on bone marrow failure in at least some patients with acquired anemias.

A Phase II Trial of the Small Molecule Pan-Bcl-2 Family Inhibitor Obatoclax Mesylate (GX15-070) Administered by a 24-h Continuous Infusion Every 2 Weeks to Patients with Chronic Idiopathic Myelofibrosis (CIMF).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3553-3553 ◽  
Author(s):  
Srdan Verstovsek ◽  
Azra Raza ◽  
Aaron D. Schimmer ◽  
Jean Viallet ◽  
Hagop Kantarjian
Keyword(s):  
Chest Pain ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Plasma Concentrations ◽  
Red Blood Cell Transfusion ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Recombinant Erythropoietin ◽  
Peripheral Edema ◽  
Transfusion Independence

Abstract Obatoclax is an antagonist of the BH3-binding groove of the bcl-2 family of anti apoptotic proteins. It activates apoptosis and has clinical activity in chronic lymphocytic leukemia (CLL; O’Brien et al, ASH 2005) and myelodysplastic syndromes (MDS ; Borthakur et al., ASH 2006). In both CLL and MDS, treatment with obatoclax has resulted in achievement of red blood cell transfusion independence in chronically anemic patients. CIMF is also frequently associated with chronic anemia as well as activating mutations of the JAK2 kinase. Activated JAK2 in turns activates Stat5 which leads to the transcriptional activation of bcl-xl. Currently ongoing two-stage trial was designed to detect a ≥30% response rate to obatoclax given as a flat dose of 60 mg by 24-h infusion every 2 weeks (2-week period equals one cycle) using the International Working Group Consensus Criteria. Patients were assessed for response every 2 weeks while on therapy. Of the 19 patients required for Stage 1, 17 have been enrolled and 14 currently have data available. Median age was 68 (range: 45–89) and 8 patients were male. JAK2 mutated in 3, wild type in 3, status unknown in 8. Prior CIMF directed therapy other then hydroxyurea and erythropoietin was given to 8 patients (1–3 regimens, median = 1). A total of 102 cycles have been administered with 3 patients still receiving obatoclax. The most common adverse events (AEs) were fatigue (57%), gait disturbance (43%), dyspnea (43%), nausea (36%), peripheral edema (36%), diarrhea (29%), chest pain (29%), chills (29%), weight loss (29%), dizziness (29%), headache (29%), cough (29%), hyperhydrosis (29%), somnolence (21%) and euphoria (21%). All were of Grades 1–2 with the exception of 3 Grade 3 AEs of peripheral edema, 2 of dyspnea, 2 of fatigue and one each of diarrhea and chest pain. Two patients died of disease related complications shortly after having received their first cycle of obatoclax. The plasma concentrations of obatoclax appeared to have reached a steady state before end of infusion. The mean ±SD plasma levels at 0, 3, and 23 hr time-points after infusion started were 0, 6.45±2.64, and 4.33±0.83 ng/mL, respectively. Two patients amongst the 8 previously treated experienced a Clinical Improvement Response persisting 6 months with increases in hemoglobin and red blood cell transfusion independence, while continuing to receive chronic recombinant erythropoietin therapy to which they had not previously responded. While still responding, one was referred for an unrelated donor allogeneic stem cell transplant while the other progressed after 6 months. Of the 6 previously untreated patients 3 are still receiving therapy with stable disease. Conclusions: Obatoclax shows activity in CIMF. Enrollment is now focusing on patients without prior CIMF-directed therapies in order to better estimate the therapeutic potential of bcl-2 family inhibition in this disease.

Diagnosis and Management of Anemia in Patients with the Myelodysplastic Syndrome

1998 ◽  
Vol 5 (2_suppl) ◽  
pp. 41-45 ◽  
Author(s):  
John M. Bennett ◽  
Peter A. Kouides
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Red Blood Cell ◽  
Red Blood Cell Transfusion ◽  
Recombinant Erythropoietin ◽  
Bone Marrow Blast ◽  
Diagnosis And Management ◽  
Specific Factors

While not appropriate for all patients with the myelodysplastic syndrome, recombinant erythropoietin (EPO) is a possible alternative to red blood cell transfusion. Specific factors such as the presence of cytopenias, the bone marrow blast percentage, and cytogenetic findings determine which patients are good candidates for treatment with EPO.

Early erythropoietin reduced the need for red blood cell transfusion in childhood hemolytic uremic syndrome—a randomized prospective pilot trial

2009 ◽  
Vol 24 (5) ◽  
pp. 1061-1064 ◽  
Author(s):  
Lars Pape ◽  
Thurid Ahlenstiel ◽  
Martin Kreuzer ◽  
Jens Drube ◽  
Kerstin Froede ◽  
...  
Keyword(s):  
Blood Cell ◽  
Hemolytic Uremic Syndrome ◽  
Red Blood Cell ◽  
Pilot Trial ◽  
Red Blood Cell Transfusion ◽  
Uremic Syndrome

Pomalidomide in Myelofibrosis with Cytopenia: First Results of the Mpnsg 01–09 Study (ClinicalTrials.gov Identifier: NCT00949364).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2840-2840
Author(s):  
Richard F Schlenk ◽  
Andreas Reiter ◽  
Norbert Gattermann ◽  
Holger Hebart ◽  
Edgar Jost ◽  
...  
Keyword(s):  
High Risk ◽  
Blood Cell ◽  
Clinical Improvement ◽  
Median Time ◽  
Red Blood Cell ◽  
Stable Disease ◽  
Disease Stage ◽  
Red Blood Cell Transfusion ◽  
Transfusion Independence ◽  
Rbc Transfusion

Abstract Abstract 2840 Background: Pomalidomide in a single arm phase-I/II study and one randomized four arm phase-II study in primary myelofibrosis (MF) and post-polycythemia vera/essential thrombocythemia (post-PV/ET) MF showed efficacy in particular with respect to improvement in anemia. To date, pomalidomide has been evaluated in MF at two dose levels, 0.5mg and 2.0 mg/day. Aims: To evaluate clinical efficacy of pomalidomide alone and in combination with prednisolone (PRED) in patients with primary or post-PV/ET MF and cytopenia. Methods: The main inclusion criteria for primary or post-PV/ET MF patients were red blood cell (RBC)-transfusion-dependence or hemoglobin <10 g/dl, and/or thrombocytopenia <50/nl and/or neutropenia <1.0/nl; patients >=50 years were eligible. Treatment consisted of pomalidomide (POM) 2mg/day; prednisone (PRED) 30mg/day was added in patients who did not respond (≤ stable disease) within three months of therapy. The primary endpoint was response assessed by IWG criteria and extended by the criterion red blood cell transfusion-independence (Gale RP et al., Leuk Res. 2011). Concurrent hydroxyurea in patients with proliferative disease and aspirin 100 mg/d in patients with platelets between 50/nl and 1000/nl were administered. The statistical design of the study was based on the Simon optimal two-stage design. Here we report on the first stage of the study. Median follow-up according to the method of Korn was 18 months. Results: Thirty-eight patients were treated with POM 2 mg/d, the median age was 71 years (range 51–83), 34% were female. Twenty-seven had primary and 11 post-PV/ET MF. Disease stage at study-entry according to the DIPSS was high-risk in 13 (34%), intermediate-2 risk in 22 (58%) and intermediate-1 risk in 3 (8%). Incidence of high-risk cytogenetics, JAK2 V617F mutation and MPL W515L mutation were 29% (10/34), 55% (21/38) and 18% (7/38), respectively. Twenty-seven patients (71%) were RBC-transfusion- and 7 (18%) platelet-transfusion dependent. Median duration of treatment with POM was 11.4 months with 5 patients continue on treatment 24+ months. PRED was added after 3 months in 19 of 28 eligible patients. POM dose-reduction (n=8, 1mg/d; n=2, 0.5mg/d) was performed after a median time of 34 days (range 3–308 days) due to fatigue (n=2), thrombo- and/or neutropenia (n=7), rash (n=1). Seven patients with high risk characteristics (n=6 RBC-transfusion dependent, n=4 high risk cytogenetics) experienced transformation into blast phase (BP), the actuarial probability of transformation to BP measured from diagnosis was 6.0% (SE 4.1%) at 2 years and 22.4% (SE 8.4%) at 5 years. Response was observed in 14 patients (37%) after a median time of 4.8 months (n=1 complete remission, n=5 clinical improvement-platelets, n=3 clinical improvement-erythrocytes, n=5 red cell transfusion-independence); 8 responders received concomitant PRED and responded after a median of three months (range 0.8–11.7 months) of the addition of PRED. In 5 of 14 responders POM dose was reduced due to toxicity, notably before response occurred. Responses were observed within the first 3 months (n=4), between month 4 to 6 (n=4) and beyond month 6 (n=6) with the latest response seen at 12.7 months. There was no correlation between response and JAK2/MPL mutation status or cytogenetics. Basophilia defined as greater than 50% increase in absolute basophil count at month 3 was in trend associated with response (p=0.06). Conclusions: POM with or without PRED in patients with different risk groups of patients with primary and post-PV/ ET MF was effective with a response rate of 37%. Based on results of this first cohort the protocol was amended; i) POM dose has been adjusted to 0.5 mg/d, ii) up-front randomization of PRED at month 4 or month 7 in patients without response but stable disease to single agent POM was introduced. Disclosures: Schlenk: Celgene: Research Funding. Off Label Use: Pomalidomide is so far not approved for the treatment of primary and secondary myelofibrosis.

scholarly journals Transfusion intensity, not the cumulative red blood cell transfusion burden, determines the prognosis of patients with myelodysplastic syndrome on chronic transfusion support

2011 ◽  
Vol 86 (3) ◽  
pp. 245-250 ◽  
Author(s):  
Arturo Pereira ◽  
Meritxell Nomdedeu ◽  
Josep-Lluís Aguilar ◽  
Mohamed Belkaid ◽  
Anna Carrió ◽  
...  
Keyword(s):  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Red Blood Cell ◽  
Red Blood Cell Transfusion

Discontinuation of Lenalidomide in Patients with Transfusion-Dependent Low- and Intermediate-1 Risk Myelodysplastic Syndromes with Del(5q): Sustained Remissions, but Not Cure.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3807-3807
Author(s):  
Aristoteles Giagounidis ◽  
Gudrun Göhring ◽  
Sabine Haase ◽  
Carlo Aul ◽  
Brigitte Schlegelberger ◽  
...  
Keyword(s):  
Blood Cell ◽  
Board Of Directors ◽  
Red Blood Cell ◽  
Cytogenetic Response ◽  
Red Blood Cell Transfusion ◽  
Advisory Committees ◽  
Transfusion Independence ◽  
Cytogenetic Remission ◽  
Rbc Transfusion

Abstract Abstract 3807 Poster Board III-743 Background Lenalidomide has high erythroid remitting activity in patients with del(5q) myelodysplastic syndrome (MDS). The actual recommendation is to continue drug administration until relapse of red blood cell transfusion dependence. We address the question whether it is safe and advisable to discontinue lenalidomide after achieving a hematologic and/or cytogenetic response Patients 13 patients (8 female, 5 male) were treated with lenalidomide between December 2003 and January 2007. Median age was 69 years. All had low- or intermediate-1 risk MDS with del(5q) chromosomal abnormality. All patients were red blood cell (RBC) transfusion dependent. All patients started treatment with 5 or 10 mg lenalidomide for 28 out of 28 days or for 21 out of 28 days. Discontinuation of lenalidomide was usually due to patient's choice, and occurred after achievement of RBC transfusion independence. Lenalidomide administration duration ranged from 6 weeks to 24 months Results Four patients had a total lenalidomide exposure of > 12 months (12, 15, 18 and 24 months), seven patients between 4 and 12 months and two patients had lenalidomide exposures of <4 months (3,5 and 1 month). Five patients achieved partial cytogenetic remission, and eight patients complete cytogenetic remission (CCR), i.e. disappearance of all del(5q) metaphases in conventional cytogenetics. Within the five patients with partial cytogenetic remission, both patients with very short lenalidomide treatment (1 and 3.5 months) achieved transfusion independence of 21 months duration. At relapse, one was progressing to RAEB-1. One patient who received lenalidomide for four months remained RBC transfusion independent for 12 months. At relapse, she resumed lenalidomide for 6 months and became transfusion independent again (16+ months). One patient received lenalidomide for eight months and remains transfusion independent after 26+ months with normalized and stable hemoglobin value. One patient received lenalidomide for 12 months and remains transfusion independent for 30+ months, but hemoglobin levels have fallen recently to 11 g/dL, indicating imminent relapse. Eight patients achieved complete cytogenetic remission: Two administered lenalidomide for 24 months, one for 18 months, three for 15 months, one for 12 months and one for 9 months. Duration of RBC transfusion independence in these patients was dependent on the length of lenalidomide administration after achievement of CCR: One patient stopped lenalidomide at the time of CCR. She remains transfusion independent after 18+ months, but del(5q) karyotype has reoccurred after 12 months. Three patients stopped lenalidomide two, four, and seven months after CCR. Transfusion-independence is ongoing at 34+, 36+ and 38+ months. In all patients del(5q) has reoccurred. Three patients discontinued after >12 months of CCR achievement. They are transfusion independent for 27+ months, 41+ months, and 66+ months. The latter patient had reoccurrence of one metaphase out of 20 with del(5q) after 60 months. Finally, one patient took lenalidomide only six months beyond CCR and remains in transfusion independence for 70+ months. However, this patient was trated with a fludarabine-containing regimen for follicular lymphoma 48 months ago Discussion Discontinuation of lenalidomide seems to be feasible in patients with del(5q) MDS, preferably in those who achieve CCR. Best results regarding long-term transfusion independence and long-term complete cytogenetic remissions are seen in patients who continue lenalidomide for 12 months after CCR achievement. Disclosures: Giagounidis: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Göhring:Celgene Corp.:. Schlegelberger:Celgene Corp.:. Kuendgen:Celgene: Honoraria. Platzbecker:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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