Achievement of red blood cell transfusion independence in red blood cell transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes correlates with serum erythropoietin levels

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.

Download Full-text

Red blood cell transfusion thresholds and Quality of Life in myelodysplastic syndromes: a pilot, feasibility study

http://isrctn.org/> ◽

10.1186/isrctn26088319 ◽

2014 ◽

Author(s):

Gillian Powter

Keyword(s):

Quality Of Life ◽

Blood Cell ◽

Feasibility Study ◽

Red Blood Cell ◽

Myelodysplastic Syndromes ◽

Red Blood Cell Transfusion ◽

Pilot Feasibility Study

Download Full-text

306 COMPARISON OF A RESTRICTIVE VERSUS LIBERAL RED BLOOD CELL TRANSFUSION POLICY IN MYELODYSPLASTIC SYNDROMES AND OTHER BONE MARROW FAILURE DISORDERS – A SYSTEMATIC REVIEW

Leukemia Research ◽

10.1016/s0145-2126(15)30307-6 ◽

2015 ◽

Vol 39 ◽

pp. S152-S153

Author(s):

Y. Gu ◽

L. Estcourt ◽

C. Doree ◽

M. Trivella ◽

S. Hopewell ◽

...

Keyword(s):

Systematic Review ◽

Bone Marrow ◽

Blood Cell ◽

Red Blood Cell ◽

Myelodysplastic Syndromes ◽

Bone Marrow Failure ◽

Red Blood Cell Transfusion

Download Full-text

Lenalidomide for patients with red blood cell transfusion-dependent IPSS low- or intermediate-1-risk myelodysplastic syndromes

10.1002/14651858.cd010413.pub2 ◽

2014 ◽

Author(s):

Yan Zeng ◽

Xin Duan ◽

Dan Long ◽

Ruiqing Zhou ◽

Songtao Yang

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Myelodysplastic Syndromes ◽

Red Blood Cell Transfusion

Download Full-text

A 36-month analysis of treatment patterns and outcomes in patients with lower-risk myelodysplastic syndromes from a prospective observational study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.7122 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 7122-7122

Author(s):

Roger M. Lyons ◽

Billie J. Marek ◽

Carole S. Paley ◽

Jason Esposito ◽

Lawrence E. Garbo ◽

...

Keyword(s):

Blood Cell ◽

Iron Overload ◽

Red Blood Cell ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Cardiac Events ◽

Risk Status ◽

Red Blood Cell Transfusions ◽

Lost To Follow Up ◽

Ophthalmologic Disorders

7122 Background: Many patients (pts) with lower-risk myelodysplastic syndromes (MDS) require chronic red blood cell transfusions for symptomatic anemia, which can result in iron overload. We present a 36-month interim analysis of a 5-year US registry that prospectively collected data on clinical events and survival in chelated vs non-chelated, transfused, lower-risk MDS pts. Methods: This multicenter, non-interventional registry enrolled 600 pts ≥18 yr old with lower-risk MDS (WHO, FAB, and/or IPSS risk stratification criteria) and transfusional iron overload (serum ferritin ≥1,000 ng/mL and/or ≥20 packed red blood cell units and/or ≥6 units every 12 wks). The chelated group included pts who had received any chelation. Results: Median age was 76 yr (range, 21–99), 57.8% were male, and risk status was 38.6% IPSS low risk and 61.4% IPSS INT-1 risk. Baseline demographics and IPSS risk status were similar between groups, although transfusion burden trended higher in chelated pts. As of April 30, 2012, 169 pts continued on the registry, and 431 discontinued (345 died, 57.5%; 61 lost to follow-up, 10.2%; and 25 other, 4.2%). In all, 264 pts (44%) received chelation therapy; 200 had ≥6 mos chelation. Overall survival (OS) and time to acute myeloid leukemia (AML) transformation were significantly longer, and the percentage of deaths was significantly lower, in chelated ≥6 mos vs non-chelated pts (P<0.0001, P=0.011 [median not reached in either group], P=0.0002, respectively. AML transformations appeared to be lower in chelated ≥6 mos pts (not significant [NS]). At baseline in non-chelated vs chelated ≥6 mos pts, there was a higher prevalence of vascular, cardiac, endocrine, and ophthalmologic disorders; this trend continued at 36 mos. Most frequent causes of death were MDS/AML, cardiac events, and infection. Use of MDS therapy was lower among non-chelated pts (non-chelated, 88.4%; ≥6 mos chelation, 93.5%; NS). Conclusions: At 36 mos,chelated pts had significantly longer OS and time to AML, as well as significantly fewer deaths. Trends toward fewer AML transformations and fewer vascular, cardiac, endocrine, and ophthalmologic disorders were observed in chelated pts.

Download Full-text

Evaluation of Cardial Iron Deposition by T2* MRI in Transfusion Dependent Patients with Myelodysplastic Syndromes.

Blood ◽

10.1182/blood.v108.11.2663.2663 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2663-2663

Author(s):

Simona Deplano ◽

Anna Di Tucci ◽

Gildo Matta ◽

Annalisa Agus ◽

Attilio Gabbas ◽

...

Keyword(s):

Blood Cell ◽

Serum Ferritin ◽

Red Blood Cell ◽

Myelodysplastic Syndromes ◽

Cardiac Mri ◽

Clinical Signs ◽

Left Ventricular ◽

Iron Deposition ◽

Red Blood Cell Transfusion ◽

Myocardial Iron

Abstract Cardiac T2* Magnetic Resonance Imaging (MRI) has been recently used to evaluate myocardial iron deposition in patients with transfusion dependent beta-thalassemia major. No comparable studies have been published for patients with myelodysplastic syndromes receiving chronic red blood cell transfusion. Therefore we measured cardiac-MRI T2* in 16 patients (10 male, 6 female) with myelodysplastic syndromes (aged 54 – 82 years, median age 67). All of them were transfusion dependent having received a median number of 60 (range 16–225) packed red blood cell transfusion equivalent to 3.2 – 45 (median 12) grams of iron. Nine have been irregularly and sporadically chelated by deferoxamine, seven were unchelated. Serum ferritin levels ranged from 1163 to 6241 mg/dl (median value 2086). None of the patients presented signs or symptoms of cardiac dysfunction at the time of the study. Cardiac-MRI T2*values obtained ranged from 5.6 to 80 (median value 46.5) milliseconds (ms). Correlation between serum ferritin and cardiac T2* value was weak ( r= 0.43, r2 =0.18). According to D. Pennel we considered as significant of myocardial iron deposition a relaxation time ≤ 20ms. Cardiac T2* was < 20ms in 3 patients who had never used iron chelators (5.6, 12.4 and 8.5 ms, respectively). They had received 39, 101 and 200 units of red blood cell transfusion, corresponding to 7.8, 20 and 40 grams of iron, respectively. Of relevance 2 of them died within few months after the end of the study and one showed early signs of left ventricular dysfunction. None of the patients with a cardiac T2* value >20 ms showed instrumental nor clinical signs of cardiac deterioration in six months follow up. No patient who had received less than 39 transfusions presented cardiac T2* value ≤20 ms. Evaluation of myocardial iron deposition by T2* cardiac MRI could be recommendable in myelodyplasia patients who had received more than 30 packed red blood cells transfusisions.

Download Full-text

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 ◽

10.1182/blood.v110.11.3553.3553 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3553-3553 ◽

Cited By ~ 1

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.

Download Full-text

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

Blood ◽

10.1182/blood.v110.11.1462.1462 ◽

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.

Download Full-text