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5q- Syndrome

Definition

  • Myelodysplastic syndrome characterized by deletion of 5q as the sole cytogenetic abnormality and no increase in blasts

Alternate Names

  • 5q minus syndrome

Diagnostic Criteria

  • Deletion of 5q is sole cytogenetic abnormality
    • Additional molecular abnormalities may be present
      • 5-10% have JAK2V16F mutation
    • Loss of Y is allowed (normal age related phenomenon)
  • Peripheral blood blasts <1%, based on 200 leukocyte differential
    • If blood blasts = 1%, designate as MDS-U
    • If blood blasts = 2-4%, or Auer rods present, designate as Refractory Anemia with Excess Blasts (RAEB)
  • Bone marrow blasts <5%, based on 500 nucleated cell differential
    • If marrow blasts 5-19%, or Auer rods present, designate as RAEB
      • Poor prognosis
  • Bone marrow megakaryocytic hyperplasia
    • Hypolobated or unilobated, small megakaryocytes
      • Increased in number
      • May loosely cluster
    • Normal or increased platelet count
      • Frequently abnormal morphology
  • Macrocytic anemia is usually present
    • Often with bone marrow erythroid hypoplasia and megaloblastoid differentiation
      • Dyssynchronous maturation of nucleus and cytoplasm of erythroid precursors
  • Dysgranulopoeisis when present may be associated with inferior survival

  • Dita Gratzinger MD PhD
    Tracy I George MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

Original posting: 10/23/11

Supplemental studies

  • Deletion of 5q must be the only cytogenetic abnormality
    • Additional molecular abnormalities may be present
      • 5-10% have JAK2V16F mutation
    • Loss of Y is allowed (normal age related phenomenon)

Differential Diagnosis

Non-neoplastic disorders may simulate myelodysplasia

  • Vitamin/micronutrient deficiencies
    • B12/folate
    • Copper
      • Ring sideroblasts present
      • Cytoplasmic vacuoles
      • May be due to
        • Zinc excess
        • Gastrectomy
        • Total parenteral nutrition
  • Infections
    • HIV
    • Parvovirus
    • HHV-6 in children
  • Toxins
    • Ethanol
    • Heavy metals
  • Growth factors
    • Granulocyte-macrophage colony-stimulating factor (GMCSF)
    • Erythropoietin
  • Drugs (numerous)
    • Chemotherapeutic agents
      • e.g. megaloblastoid change with folate antagonists
    • Valproic acid, MMF (mycophenolate mofetil), Ganciclovir
      • Pseudo-Pelger-Helger anomaly
  • Autoimmune/rheumatologic
    • e.g. systemic lupus erythematosus
  • Congenital
    • Congenital dyserythropoietic anemias
    • Inherited bone marrow failure syndromoes (Fanconi etc.)
    • Monocytopenia immunodeficiency syndrome

Myelodysplastic Syndromes

  Circulating Blasts Marrow Blasts Ring Sideroblasts Dysplastic Lineages Cytopenias
RCUD <1% <5% <15% Any 1 lineage 1 or 2
RARS 0 <5% ≥15% Only erythroid 1 or 2
RCMD <1% <5% Variable 2 or more lineages 1, 2 or 3
RAEB-1 <5% 5-9% Variable 1 or more 1, 2 or 3
RAEB-2 5-19% 10-19% or Auer rods Variable 1 or more 1, 2 or 3
del(5q) <1% <5% Variable Frequently hypolobated small megakaryocytes Usually 1 (anemia)
  • RCUD = refractory cytopenia (anemia, neutropenia or thrombocytopenia) with unilineage dysplasia; RARS = refractory anemia with ringed sideroblasts; RCMD = refractory cytopenia with multilineage dysplasia; RAEB = refractory anemia with excess blasts; del(5q) = 5q- syndrome
  • All MDS must not have absolute monocytosis
  • If chemotherapy or radiation therapy related, should be reported as "therapy-related myeloid neoplasm"
  • In children, consider provisional WHO entity "refractory cytopenia of childhood" for low blast count MDS
  • Myelodysplastic syndrome unclassifiable (MDS-U)
    • Must not meet criteria of any specific WHO category
    • Persistent cytopenia(s) with any of the following:
      • Unilineage marrow dysplasia with pancytopenia OR
      • <1% blasts in blood, <5% blasts in marrow and cytogenetic abnormalities but no lineage with ≥10% dysplastic forms OR
      • Findings of RCUD or RCMD but with 1% blasts in peripheral blood
        • (2-4% blasts would be classified as RAEB-1)
    • Nonclonal causes must be excluded

 

Clinical

  • 2/3-3/4 female
    • Contrasts with MDS overall, which is male predominant
  • Mean age 74 years
  • Responds to lenalidomide (antiangiogenic thalidomide analog)
  • 5q- syndrome has a low rate (<10%) of transformation to acute leukemia
  • Median survival 145 months
By defninition, 5q- syndrome is 0 or 0.5 points in IPSS, depending on the number of cytopenic lineages

International Prognostic Scoring System (IPSS)

Points are assigned based on abnormal findings

Points: 0 0.5 1 1.5 2
BM blast % <5 5-10 - 11-20 21-30
Cytogenetic Group Good Intermediate Poor    
Number of cytopenic lineages 0-1 2-3      
  • Cytogenetic groups
    • Good: Normal, -Y, del(5q), del(20q)
    • Intermediate: All others
    • Poor: Complex, chromosome 7 abnormalities
  • Cytopenias
    • Hemoglobin <10 mg/dl
    • Absolute neutrophil count <1.8 x 103/μL
    • Platelets <100 x 103/μL

Risk groups are determined based on points assigned as above

Risk Group Points Median Survival Evolution to Acute Leukemia
Low 0 5.7 years 9.4 years
Intermediate-1 0.5-1.0 3.5 years 3.3 years
Intermediate-2 1.5-2.0 1.2 years 1.1 years
High >2.5 0.4 years 0.2 years
  • Treatment based on risk group assigned and ability to tolerate therapy including
    • Supportive care
    • Immunosuppressive agents
    • Bone marrow transplantation
    • Intensive cytotoxic treatment
    • Demethylating agents
    • Farnesyl transferase inhibitors

Blood 89:2079, 1997

 

Classification / Lists

WHO 2008 Classification of Myeloid Neoplasms

Myeloproliferative Neoplasms (MPN)

Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)

Myelodysplastic Syndromes (MDS)

Therapy Related Myeloid Neoplasms

 

Bibliography

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