Changing the Treatment Paradigm in Myelodysplastic Syndromes

Mufti, Ghulam J.; Chen, Tara L.

doi:10.1177/107327480801504s03

Cited by 17 publications

(12 citation statements)

References 54 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secondly the dose of alemtuzumab used might be too high for high risk AML and MDS patients. Although the British experience with alemtuzumab‐based regimens in MDS was favourable (Mufti & Chen, 2008), the use of radioimmunotherapy might aggravate the immunosuppressive state for a longer period of time and might additionally suppress the activation of allogeneic effector cells. We therefore decided to amend the current protocol and reduce the dose of alemtuzumab to 50 mg. Of course, one has to be aware that strategies harnessing GvL reactions might put several of these older patients at an increased risk for life‐threatening acute and chronic GvHD.…”

Section: Discussionmentioning

confidence: 99%

¹⁸⁸Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation

et al. 2010

View full text Add to dashboard Cite

SummaryThe addition of radioimmunotherapy to conventional and reduced-intensity conditioning has been shown to be feasible and effective. Within an ongoing prospective phase II trial, 22 patients with advanced myeloid malignancies and a median age of 65 years (range 54-76) received anti-CD66 Rhenium radioimmunotherapy followed by fludarabine (150 mg/m 2 ), busulfan (8 mg/ kg) and alemtuzumab (75 mg) before allogeneic haematopoietic stem cell transplantation from matched sibling (n = 7) and unrelated donors (n = 15). The extramedullary toxicity in the first 100 d post-transplantation was limited and all patients engrafted with complete donor chimaerism. The incidence of non-relapse mortality at day 100 and after 2 years was 4AE5% and 23%, respectively. The probability of overall survival at 2 years was 40%. A comparison with a younger historical cohort (median age 57 years) having received the same dose of fludarabine and busulfan but neither radioimmunotherapy nor alemtuzumab showed no difference in outcome. Although the use of alemtuzumab reduced the incidence of acute graftversus-host-disease, it was associated with a relapse incidence of 40% despite the incorporation of radioimmmunotherapy. In summary, we confirmed the feasibility of combined radioimmunotherapy and reduced-intensity conditioning in elderly patients. Further optimisation, probably involving less T cell depletion, is necessary before a randomized comparison with standard conditioning can be planned.

show abstract

Section: Discussionmentioning

confidence: 99%

¹⁸⁸Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Until some years ago, active treatment options for patients with high-risk MDS were limited to hematopoietic stem cell transplantation (HSCT) and chemotherapy. While HSCT remains the only potentially curative treatment in eligible candidates, it is rarely applicable to the majority (mainly due to advanced age and/or comorbidities) [6], and chemotherapy has shown limited efficacy [7,8] and should be reserved for patients with a normal karyotype. However, alternative nonaggressive treatment options that can improve outcomes in a broader range of patients are now available or are under development.…”

Section: Introductionmentioning

confidence: 99%

Minimizing risk of hypomethylating agent failure in patients with higher-risk MDS and practical management recommendations

et al. 2014

View full text Add to dashboard Cite

In Europe, azacitidine is the only hypomethylating agent approved for the treatment of patients with int-2-/high-risk myelodysplastic syndromes, offering significantly improved survival compared with conventional care. However, not all patients treated with azacitidine respond to treatment, and the vast majority of responders subsequently relapse. Currently, no standard care regimens have been established for patients after failure of azacitidine. Here, we discuss treatment options after loss of response or progression on azacitidine. In addition, we briefly consider optimization of first-line treatment along with potential biomarkers for identifying and monitoring response during treatment with azacitidine.

show abstract

“…More recently, alemtuzumab has also been administered in patients with MDS (30,31). The primary rational of this approach has been the observation that T-celltargeting immunosuppressive agents, like anti-thymocyte globulin, are effective in a subgroup of patients, especially those with hypoplastic MDS (32,33). Alemtuzumab was also found to induce remarkable responses and even remission in a few patients with MDS (30,31).…”

Section: Introductionmentioning

confidence: 99%

Identification of Campath-1 (CD52) as Novel Drug Target in Neoplastic Stem Cells in 5q-Patients with MDS and AML

Blatt

Herrmann

Hoermann

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The CD52-targeted antibody alemtuzumab induces major clinical responses in a group of patients with myelodysplastic syndromes (MDS). The mechanism underlying this drug effect remains unknown.Experimental Design: We asked whether neoplastic stem cells (NSC) in patients with MDS (n ¼ 29) or acute myelogenous leukemia (AML; n ¼ 62) express CD52.Results: As assessed by flow cytometry, CD52 was found to be expressed on NSC-enriched CD34 þ /CD38 À cells in 8/11 patients with MDS and isolated del(5q). In most other patients with MDS, CD52 was weakly expressed or not detectable on NSC. In AML, CD34 þ /CD38 À cells displayed CD52 in 23/ 62 patients, including four with complex karyotype and del(5q) and one with del(5q) and t(1;17;X). In quantitative PCR (qPCR) analyses, purified NSC obtained from del(5q) patients expressed CD52 mRNA.We were also able to show that CD52 mRNA levels correlate with EVI1 expression and that NRAS induces the expression of CD52 in AML cells. The CD52-targeting drug alemtuzumab, was found to induce complement-dependent lysis of CD34 þ /CD38 À /CD52 þ NSC, but did not induce lysis in CD52 À NSC. Alemtuzumab also suppressed engraftment of CD52 þ NSC in NSG mice. Finally, CD52 expression on NSC was found to correlate with a poor survival in patients with MDS and AML. Conclusions:The cell surface target Campath-1 (CD52) is expressed on NSC in a group of patients with MDS and AML. CD52 is a novel prognostic NSC marker and a potential NSC target in a subset of patients with MDS and AML, which may have clinical implications and may explain clinical effects produced by alemtuzumab in these patients. Clin Cancer Res; 20(13); 3589-602. Ó2014 AACR.

show abstract

Changing the Treatment Paradigm in Myelodysplastic Syndromes

Cited by 17 publications

References 54 publications

¹⁸⁸Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation

¹⁸⁸Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation

Minimizing risk of hypomethylating agent failure in patients with higher-risk MDS and practical management recommendations

Identification of Campath-1 (CD52) as Novel Drug Target in Neoplastic Stem Cells in 5q-Patients with MDS and AML

Contact Info

Product

Resources

About

Changing the Treatment Paradigm in Myelodysplastic Syndromes

Cited by 17 publications

References 54 publications

188Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation

188Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation

Minimizing risk of hypomethylating agent failure in patients with higher-risk MDS and practical management recommendations

Identification of Campath-1 (CD52) as Novel Drug Target in Neoplastic Stem Cells in 5q-Patients with MDS and AML

Contact Info

Product

Resources

About

¹⁸⁸Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation

¹⁸⁸Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation