Immunosuppressive Therapy: Exploring an Underutilized Treatment Option for Myelodysplastic Syndrome

Haider, Mintallah; Ali, Najla Al; Padron, Eric; Epling-Burnette, Pearlie K.; Lancet, Jeffrey E.; List, Alan F.; Komrokji, Rami

doi:10.1016/j.clml.2016.02.017

Cited by 21 publications

(15 citation statements)

References 7 publications

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“…44 However, reports have varied widely in what characteristics predict response to IST, and the National Institutes of Health response model could not be validated in some studies. 45,46 In our patient cohort, we were not able confirm the predictive value of several previously described biomarkers of response. Age, prior transfusion dependence, MDS risk assessment scores, presence of PNH or LGL clones, HLA DR15 positivity, and gene mutations did not appear to predict response to IST.…”

Section: Discussioncontrasting

confidence: 83%

“…48 On the contrary, one prior study in MDS reported no difference in the response rate achieved with horse ATG vs rabbit ATG 47 ; however, this was a much smaller study of just 35 patients. In addition, ATG in combination with cyclosporine was superior to all other IST regimens examined regarding the achievement of TI in univariate analysis, which is similar to studies in MDS 45 and in severe aplastic anemia. 49 There are limited data regarding the effect of somatically recurrent genetic mutations on response to IST among patients with MDS.…”

Section: Discussionsupporting

confidence: 71%

“…These include younger age (,65 years) and limited prior transfusion history (,2 years), as well as use as first-line treatment (or after lenalidomide), low blast percentage with hypocellular marrow, and good prognostic karyotype, in addition to HLA DR15 and PNH clone positivity and a higher CD8 1 terminal memory T-cell percentage. 5,6,[44][45][46] On the basis of the patient's age, the duration of transfusion dependence before IST, and the HLA-DR15 genotype, the National Institutes of Health response model for IST in MDS was developed. 44 However, reports have varied widely in what characteristics predict response to IST, and the National Institutes of Health response model could not be validated in some studies.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the Median OS: TI achieved: Not reached (95% CI: 76.9-not reached months) TI not achieved: 26.6 months (95% CI: 20.9-46.6 months) TI not achieved (n29) TI achieved (n18) limited number of data points for bone marrow cellularity as well as HLA DR15 positivity and presence of a PNH clone could have played a role as well. However, apart from the National Institutes of Health cohort of patients, 13,44 in most of the other studies examining predictive factors for IST in MDS, 5,6,45,47 bone marrow cellularity and HLA DR15 status were assessed in only 10 to 20 patients, whereas PNH clones were only tested for in less than 10 patients if tested for at all. In comparison, in our study, in 70 to 80 patients, data on bone marrow cellularity, and in 40 to 50 patients, data on HLA DR15 and PNH clonal status was available to correlate with response and OS.…”

Section: Discussionmentioning

confidence: 99%

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The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort

et al. 2018

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Most studies of immunosuppressive therapy (IST) in myelodysplastic syndromes (MDS) are limited by small numbers and their single-center nature, and report conflicting data regarding predictors for response to IST. We examined outcomes associated with IST and predictors of benefit in a large international cohort of patients with MDS. Data were collected from 15 centers in the United States and Europe. Responses, including red blood cell (RBC) transfusion independence (TI), were assessed based on the 2006 MDS International Working Group criteria, and overall survival (OS) was estimated by Kaplan-Meier methods. Logistic regression models estimated odds for response and TI, and Cox Proportional Hazard models estimated hazards ratios for OS. We identified 207 patients with MDS receiving IST, excluding steroid monotherapy. The most common IST regimen was anti-thymocyte globulin (ATG) plus prednisone (43%). Overall response rate (ORR) was 48.8%, including 11.2% (95% confidence interval [CI], 6.5%-18.4%) who achieved a complete remission and 30% (95% CI, 22.3%-39.5%) who achieved RBC TI. Median OS was 47.4 months (95% CI, 37-72.3 months) and was longer for patients who achieved a response or TI. Achievement of RBC TI was associated with a hypocellular bone marrow (cellularity < 20%); horse ATG plus cyclosporine was more effective than rabbit ATG or ATG without cyclosporine. Age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST. IST leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows.

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Section: Discussioncontrasting

confidence: 83%

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort

et al. 2018

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“…[58, 59] A single center study of immunosuppressive therapy (IST), including ATG and cyclosporine, demonstrated response rate in low risk disease similar to other standard therapies, however high risk disease patients did not respond as well to IST. [60] A more recent study presented in abstract form was one of the largest studies of immunosuppressive therapy in MDS. Immunosuppressive therapy in this large cohort showed overall response rate of 45%, leading to transfusion independence in 39% of patients.…”

Section: Introductionmentioning

confidence: 99%

Disordered Immune Regulation and its Therapeutic Targeting in Myelodysplastic Syndromes

Ivy

Ferrell

2018

Curr Hematol Malig Rep

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Immune alterations in MDS are complex, heterogeneous, and intertwined with clonal hematopoiesis and stromal cell dysfunction. Inflammation in MDS proceeds as a vicious cycle, mediated in large part by secreted factors, which induce cell death and activate innate immune signaling. Therapeutic targeting of this variable immune dysregulation has led to modest responses thus far, but incorporation of the growing repertoire of immunotherapy brings new potential for improved outcomes. The immune milieu is variable across the spectrum of MDS subtypes, with a changing balance of inflammatory and suppressive cellular forces from low- to high-risk disease.

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Be careful of the masquerades: differentiating secondary myelodysplasia from myelodysplastic syndromes in clinical practice

Shallis

Podoltsev

et al. 2018

Ann Hematol

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In patients suspected to have myelodysplastic syndrome (MDS), especially in those patients without cytogenetic abnormalities or blast excess, accurate morphologic review by an expert hematopathologist and meticulous exclusion of other secondary causes of myelodysplasia are vital to establish the diagnosis. Errors in diagnosis can lead to dangerous consequences such as the administration of hypomethylating agents, lenalidomide, or even the use of intensive chemotherapy or allogeneic hematopoietic cell transplantation in patients who do not have an underlying MDS or even a malignant hematopoietic process. Additionally, beyond the possible harm and lack of efficacy of such therapies if the diagnosis of MDS is erroneous, the secondary myelodysplasia and resultant cytopenias are not likely to resolve unless the underlying etiology is identified and addressed. Discriminating a malignant process such as MDS from non-malignant secondary myelodysplasia can be quite challenging, and community hematologists/oncologists should consider referral to specialized physicians (both clinical experts and experienced hematopathologists) if there is any doubt regarding the diagnosis. In this article, we present a representative case series of patients from our own practice who posed diagnostic dilemmas and propose a systematic approach for assessment for secondary causes of myelodysplasia.

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Immunosuppressive Therapy: Exploring an Underutilized Treatment Option for Myelodysplastic Syndrome

Cited by 21 publications

References 7 publications

The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort

The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort

Disordered Immune Regulation and its Therapeutic Targeting in Myelodysplastic Syndromes

Be careful of the masquerades: differentiating secondary myelodysplasia from myelodysplastic syndromes in clinical practice

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