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11 Nov 2018

Myelodysplasia: Potential Therapies

Dr. Paul S. Anderson

Based on known data regarding MDS and its etiology as well as potential therapies (see below) there is a low probability of ‘cure’ using known therapies.  Supportive care is the mainstay of therapy especially in patients over 60 years of age. Oxidative treatments are indicated, as well as transplantation, growth factors, demethylating agents and immunosuppression.

Supportive therapies to consider:

  • IV Nutrients including glutathione
  • ALA, Poly MVA, Silibinin, Curcumin etc…
  • Maitaki
  • Oral K2 Analogues

Oxidative therapies (separate from supportive IV therapy) to consider:

  • O3 – UVBI

Selected Resources:

From: Annu. Rev. Med. 2005. 56:1–16

“Supportive care generally is the mainstay of therapy. Patients should be treated with erythrocytes for symptomatic anemia. To reduce the risk of iron overload in patients who receive >10 erythrocyte transfusions per year, therapy with an iron chelator should be used, e.g., by bolus subcutaneous administration.”

“Allogeneic bone marrow transplantation currently offers the only potentially curative treatment, but this form of therapy is not available for the typical MDS patient, who is >60 years of age. Therapy with erythropoietin and G-CSF has improved the quality of life of selected patients. The development of small molecules directed against specific molecular targets with minimal adverse effects is the hope for the future. Innovative uses of immunomodulatory agents and the optimizing of cytotoxic treatment should continue to help in the treatment of MDS.”

“Recent studies in which intensive cytotoxic treatment was administered to younger individuals with high-risk MDS have produced remission rates ranging from 22% to 79%. As a consequence of the further improved supportive care in patients receiving intensive cytotoxic treatment, the remission rate achieved in high-risk MDS patients is comparable with those for patients with de novo AML.”

From:  Wesa KM, Cunningham-Rundles S, Klimek VM, Vertosick E, Coleton MI, Yeung KS, Lin H, Nimer S, Cassileth BR. Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study. Cancer Immunol Immunother. 2015 Feb;64(2):237-47. doi: 10.1007/s00262-014-1628-6. Epub 2014 Oct 29. PMID: 25351719

BACKGROUND: Myelodysplastic syndromes (MDS) are characterized by ineffective erythropoiesis with dysplastic bone marrow leading to peripheral cytopenia, risk of infection, and progression to acute myelogenous leukemia. Maitake mushroom beta-glucan, a dietary supplement, stimulates hematopoietic progenitor cell differentiation, granulocyte colony-stimulating factor production, and recovery of peripheral blood leukocytes after bone marrow injury. This phase II trial examined the effects of Maitake on innate immune function in MDS.

METHODS: Myelodysplastic syndromes patients with International Prognostic Scoring System Low- and Intermediate-1-risk disease received oral Maitake extract at 3 mg/kg twice daily for 12 weeks. Primary endpoints included neutrophil count and function tested as endogenous or stimulated neutrophil production of reactive oxygen species (ROS) by flow cytometry compared with age-matched healthy controls (HC). ROS activators were Escherichia coli, phorbol ester, and the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Complete blood counts, chemistry panels, iron studies, and monocyte function were evaluated.

RESULTS: Of 21 patients enrolled, 18 completed the study and were evaluable. Maitake increased endogenous (basal) neutrophil (p = 0.005) and monocyte function (p = 0.021). Pre-treatment monocyte response to E. coli was reduced in MDS patients compared with HC (p = 0.002) and increased (p = 0.0004) after treatment. fMLP-stimulated ROS production response also increased (p = 0.03). Asymptomatic eosinophilia occurred in 4 patients (p = 0.014). Other changes in albumin, hemoglobin, and total protein were not clinically relevant.

CONCLUSIONS: Maitake was well tolerated. Enhanced in vitro neutrophil and monocyte function following treatment demonstrate that Maitake has beneficial immunomodulatory potential in MDS. Further study is warranted.

From: Takami A, Asakura H, Nakao S. Menatetrenone, a vitamin K2 analog, ameliorates cytopenia in patients with refractory anemia of myelodysplastic syndrome. Ann Hematol. 2002 Jan;81(1):16-9. Epub 2001 Dec 8.

Vitamin K2 induces differentiation of leukemic cell lines and apoptosis of immature blasts in myelodysplastic syndrome (MDS). We recently reported a case of MDS-refractory anemia (MDS-RA) with trilineage hematologic response to oral administration of menatetrenone, a vitamin K2 analog. To determine a possible role of this agent in treatment of MDS-RA, we conducted a prospective randomized trial assessing the safety and efficacy of menatetrenone. A total of 18 consecutive patients newly diagnosed with MDS-RA were randomized to receive either 45 mg of oral menatetrenone (group 1) or no menatetrenone (group 2). Administration of menatetrenone was well tolerated. Of the nine patients in group 1 (56%), five improved with menatetrenone treatment while only one (11%) of the group 2 patients improved. Three patients (33%) showed a major response in absolute neutrophil count (ANC), two (22%) showed a major response in hemoglobin concentration, and two of the nine (22%) showed a major response in platelet count. The ANC of group 1 patients rose after treatment, while that of group 2 patients decreased slightly at follow-up after 16 weeks ( p=0.03). Significant improvement was also seen in final platelet count ( p=0.01), but not in hemoglobin concentration. Given the absence of toxicity, menatetrenone can be recommended for all patients with MDS-RA.