Pathological iron deposition in mitochondria of erythroid precursors
Pathologic finding
🚫a specific diagnosis!
Broad classification of sideroblastic anemias.
1. Congenital
-Syndromic
-Non-syndromic
2. Acquired
-Clonal
-Metabolic
-Drugs
WHO defined types of sideroblasts
Type 1: <5 siderotic granules in cytoplasm.
Type 2: ≥5 granules but no perinuclear distribution.
Type 3 = ringed sideroblast: ≥ 5 granules in a perinuclear position, surrounding nucleus or encompassing one third of nuclear circumference.
X-linked sideroblastic anemia with ataxia (XLSA/A)
Early onset motor delay, spinocerebellar hypoplasia
Ataxia with severe cerebellar hypoplasia
Mild sideroblastic anemia
Mutation ABC7 transporters:
Transports components involved in construction of Fe-S clusters.
Board Review Question!
What is your differential for an infant with anemia and pancreatic insufficiency? 1. Shwachman-Diamond syndrome 2. Pearson’s syndrome
Pearl: Pearson’s syndrome has ringed sideroblasts while Shwachman-Diamond syndrome does not.
Pearson's syndrome = Mitochondrial DNA
Presents in infants
-Lactic acidosis
-Pancreatic insufficiency
-Myopathy
Spectrum of Kearns-Sayre syndrome
Pancytopenia, ringed sideroblasts
Vacuolization hematopoietic precursors
Maternally inherited
4977 bp deletion mitochondrial genome
Acquired Sideroblastic Anemia
Clonal
-RARS
-RARS-T
-RCMD-RS
Metabolic
-Copper deficiency
-Zinc toxicity
Drugs
-Chloramphenicol
-INH
-Linezolid
Alcoholism
Hypothermia
Clonal
RARS: dysplasia confined to the erythroid cell lineage.
-All have SF3B1 mutation
RARS-T: Anemia+thrombocytosis
-SF3B1+JAK2 V617F which frequently has the
RCMD-RS: MDS with additional dysplastic features involving granulopoiesis and/or megakaryopoiesis.
-SF3B1
Copper deficiency
⬇️Cu disrupts iron metabolism
⬇️Intestinal Fe absorption 2/2 lack of ceruloplasmin and ferroxidase function in haphaestin
⬇️ferrous iron in mitochondria 2/2 ⬇️cytochrome c oxidase (necessary for heme synthesis)
⬆️Zinc excess causes ⬇️copper
-⬇️ Cu absorption
Drugs
INH: Interferes with B6 metabolism
Depletes ALAS2 of pyridoxal phosphate
Two of these disease are seen often on both the heme consult service and boards.
Cold Agglutinin Disease
Hemolytic anemia precipitated by cold
Monoclonal IgM binds RBCs (I antigen), agglutination, and fixes complement in cold->hemolysis
DAT+ for C3 and - for IgG
Associated with IgM gammopathies/LPL
Polyclonal form after Mycoplasma infection
Rx = Rituximab
Early stage DLBCL Tweetorial of all key trials from a presentation I just gave #Goodman_heme
See last slide/Tweet for my conclusions
SWOG 8736:
>18 years
Bulk (>10 cm) allowed
CHOPx 3+IFRT vs. CHOP x 3 +IFRT
OS⬆️with IFRT but no difference in OS with extended f/u
18 year f/u
ECOG 1484
>16 years
Bulk (>10 cm) allowed
CHOP x 8 if CR (by CT) randomized to IFRT vs observation
DFS improved with IFRT
No difference in OS
GELA/LNH 93-1
No adverse risk factors on aaIPI
Age <60 years
Bulk (> 10 cm) allowed
ACVBP x 3 vs CHOP x 3 + IFRT
EFS and OS improved with chemo alone
Very young favorable group but chemo alone works!