Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin

Lim, Zi Yi; Killick, Sally; Germing, Ulrich; Cavenagh, Jamie; Culligan, Dominic; Bacigalupo, Andrea; Marsh, Judith; Mufti, Ghulam J.

doi:10.1038/sj.leu.2404747

Cited by 132 publications

(100 citation statements)

References 27 publications

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“…The most important predictor for response has been the presence of marrow hypocellularity [44]. This is in line of the results of Mufti et al in London [45].…”

Section: Immune Therapysupporting

confidence: 83%

Myelodysplastic syndromes: 2012 update on diagnosis, risk‐stratification, and management

Garcia‐Manero

2012

American J Hematol

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Disease Overview: The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older male and in individuals with prior exposure to cytotoxic therapy.Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is complementary but not diagnostic.Risk‐stratification: Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow and cytogenetic characteristics. The most commonly used system is the International Prognostic Scoring System. IPSS is likely to be replaced by a new revised score (IPSS‐R) and by the incorporation of new molecular markers recently described.Risk‐adapted therapy: Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts, and, more recently, cytogenetic profile. Goals of therapy are different in lower risk patients than in higher risk. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML. In higher risk, the goal is to prolong survival. Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation. The use of lenalidomide has significant clinical activity in patients with lower risk disease, anemia and a chromosome 5 alteration. 5‐azacitidine and decitabine have activity in higher risk MDS. 5‐azacitidine has been shown to improve survival in higher risk MDS. A number of new molecular lesions have been described in MDS that may serve as new therapeutic targets or aid in the selection of currently available agents. Additional supportive care measures may include the use of prophylactic antibiotics and iron chelation.Management of progressive or refractory disease: At the present time there are no approved interventions for patients with progressive or refractory disease particularly after hypomethylating based therapy. Options include cytarabine based therapy, transplantation and participation on a clinical trial. Am. J. Hematol. 87:692–701, 2012. © 2012 Wiley Periodicals, Inc.

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“…The most important predictor for response has been the presence of marrow hypocellularity [44]. This is in line of the results of Mufti et al in London [45].…”

Section: Immune Therapysupporting

confidence: 83%

Myelodysplastic syndromes: 2012 update on diagnosis, risk‐stratification, and management

Garcia‐Manero

2012

American J Hematol

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“…The response and overall survival rates in this study were higher than 20%-40% and 50%-70%, respectively, achieved in adults. [9][10][11][12][13] This difference can be explained, in part, by the careful selection of pediatric subjects for IST. In fact, previous studies in adults included patients with different MDS subtypes such as refractory anemia, refractory anemia with ringed sideroblasts, and refractory anemia with excess of blasts.…”

Section: Discussionmentioning

confidence: 99%

“…In the EWOG-MDS studies, only children with RCC, a hypocellular bone marrow, and a karyotype other than monosomy 7/7q-or three or more chromosomal aberrations were eligible for IST because these variables were known to be associated with a favorable response to IST and a low risk of disease progression. [11][12][13]26 Seven patients with RCC and a normocellular bone marrow who received IST were excluded from this analysis because they did not meet the eligibility criteria. Indeed, only one of these patients responded to IST, supporting our recommendation to use IST only in children with a hypocellular bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

Yoshimi

Heuvel‐Eibrink

Baumann³

et al. 2013

Haematologica

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Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090) Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood 16 In addition, a number of non-randomized studies showed inferior results for rabbit-ATG in adults and children with aplastic anemia. [17][18][19] No published series of patients with aplastic anemia has shown that rabbit-ATG is superior to horse-ATG in the context of first-line IST. [16][17][18][19][20][21][22] To date, there have only been a few reports on the efficacy of IST with rabbit-ATG in patients with MDS. 10,23,24 In this study, we compared the outcome of IST using horse-ATG with that of IST using rabbit-ATG in a large series of children with RCC. Methods Selection of patients for immunosuppressive therapyBone marrow and peripheral blood smears and bone marrow biopsies were centrally reviewed by reference pathologists in each country and the diagnosis of RCC was made according to the WHO criteria. 1,25 Fanconi anemia was excluded in all patients. Patients with RCC aged ≤18 years were enrolled in the prospective studies EWOG-MDS-98 (05/1998-12/2006) and EWOG-MDS-2006 (01/2007-08/2011. These studies were approved by the institutional review board of each participating institution. Written informed consent was provided by the patients' parents according to the Declaration of Helsinki.Patients with RCC are treated according to a risk-based strategy (Figure 1). Because of a high risk of disease progression, all patients with monosomy 7/7q-or three or more chromosomal aberrations undergo allogeneic hematopoietic stem cell transplantation (HSCT). 26 For patients without these unfavorable karyot...

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“…These clinical features include younger age (i.e. <60 years), lower risk disease, marrow hypocellularity, HLADR15 histocompatibiility type, evidence for a paroxysmal nocturnal haemoglobinuria clone and more recent disease duration (Saunthararajah et al, 2002;Lim et al, 2007;Sloand et al, 2008). Of these variables, younger age (Sloand et al, 2008) and marrow hypocellularity (Lim et al, 2007) appear to be the most useful predictors of IST response in lower risk patients.…”

Section: Management Of Lower Risk Diseasementioning

confidence: 99%

Current therapeutic approaches for patients with myelodysplastic syndromes

Greenberg

2010

Br J Haematol

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SummaryThe myelodysplastic syndromes (MDS) are a heterogeneous spectrum of disorders requiring selective therapy based on patients' specific clinical features, predominantly their prognostic subgroups, age and performance status. Guidelines for management of patients with MDS have been generated by a number of national panels. This review focuses on evidencebased data supporting therapeutic approaches, which have also been recommended by the US National Comprehensive Cancer Network MDS Panel, with discussion of accessibility of recommended drugs in the US and in other countries. For lower risk disease (International Prognostic Scoring System Low and Intermediate-1) therapy is aimed at haematological improvement whereas for higher risk disease (Intermediate-2 and High) treatment focuses on altering disease natural history. Recent information regarding additional clinical and biological features has provided useful parameters for assessing disease prognosis that aid risk-based management decisions. The rationale for use of low versus high intensity therapies with these agents, including allogeneic haematopoietic stem cell transplantation, is discussed in detail.

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Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin

Cited by 132 publications

References 27 publications

Myelodysplastic syndromes: 2012 update on diagnosis, risk‐stratification, and management

Myelodysplastic syndromes: 2012 update on diagnosis, risk‐stratification, and management

Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

Current therapeutic approaches for patients with myelodysplastic syndromes

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