(The following are notes taken by Lesley B. who participated at Camp Sunshine 2006)
This information is included in an article entitles "Improving Clinical Care and Elucidating the
Pathophysiology of Diamond Blackfan Anemia: An Update from the Diamond Blackfan Anemia Registry" by
Drs. Lipton, Zyskin, and Vlachos and Eva Atsidaftos, MA. Published online 29 November 2005 in Wiley
InterScience and hopefully soon in journals worldwide.
My notes are in [ ], otherwise the info is off the hand-out pages.
Childhood Pure Red Cell Aplasia can be either congenital (such as DBA) or acquired (such as TEC, infection
associated, malignancy associated, from drugs/toxins, etc.).
The diagnostic criteria for DBA are: age less than 1 year, moderate to severe macrocytic anemia,
reticulocytopenia (low retic count), normal bone marrow cellularity with a paucity of erythroid precursors.
Major criteria that support a DBA diagnosis are: the RPS19 mutation or a positive family history. Minor
supportive criteria are: elevated erythrocyte adenosine deaminase (eADA) activity (normal ADA is 0.20-0.98, in
DBA you see 0.45-5.11), congenital anomalies, elevated fetal hemoglobin, no evidence of another type of bone
marrow failure. [My notes say that you should have all the diagnostic criteria and a couple of the supporting
criteria to have classical DBA.]
A comparison of DBA and TEC (transient erythroblastopenia of childhood): DBA is inherited, TEC is aquired.
50% of DBA patients show some physical anomaly [she's including short stature here], no TEC patients do.
There are also some CBC count differences, but the main ones would be that DBA his increased eADA
while TEC doesn't, DBA has increase mean corpuscle volume (MCV - the size of the red blood cell), and
generally TEC has no increase in fetal hemoglobin except during recovery.
The DBA Registry (DBAR) was formally established in 1993. It's objective is to develop a demographic, clinical
and laboratory database in order the facilitate the study of the epidemiology and biology of DBA. To advertise
the DBA they had initial mailing to physicians, ads in medical journals and meetings, listings at
other organizations. They register patients and have a 14 page questionnaire completed by
patient/parents/physicians. They do follow-ups also.
There are 420 patients in the registry, 349 are alive, 36 are deceased, 30 have insufficient data, and 5 have been
excluded for incorrect diagnosis. Male:female ratio is 1.07:1. Median age at presentation is 8 weeks (range is
birth to 6 years). 93% of the DBAR patients present during the first year. Median age at diagnosis is 12 weeks
(range is birth to 26 years). This doesn't include "non-classical" cases.
Distribution by birth year:
a.. 1949-1967: median 2.0 +/- 1.2 cases/year
b.. 1968-1977: 5.5 +/- 2.2
c.. 1978-1987: 11.0 +/-3.6
d.. 1988-1997: 17.0 +/-3.6
e.. 1998-2004: 8.0 +/-1.1
20-40 new cases per year are expected. [There statistically should be about 600 cases in North America.]
Recommended treatment options for DBA are:
a.. Transfusions until 6-12 months of ages [the newest recommendation from Dr. V and Lipton is not to start
steroids before 6 months, and sometimes 12-18 months. This is to allow for the critical growth during this time
and also to get immunizations.]
b.. Corticosteroid therapy
a.. Initial dose of 2 mg/kg/day
b.. Response should be in 2-4 weeks [an adequate Hb is 8-10 or what the patients needs at the time]
c.. Then taper to the lowest effective dose, which must be 0.5 mg/kg/day or 1 mg/kg/every other day or it's
not a low enough dose.
d.. If there's no response, wean and discontinue
c.. Stem cell transplantation
d.. Alternative therapies
a.. Metoclopromide (Reglan) [about 10% respond]
b.. Cyclosporine A +/- Anit-thymocyte globulin [has more side effects than steroids]
c.. Erythropoietin (Epogen, Procrit, Aranesp)
d.. Rituximab (Rituxan) [an immune suppressant - there's an open study going on about it. It affects B cells. 1
person is responding to it but has white cell problems. They have no idea why it would work.]
e.. Revlimid [for chromosome 5Q problems. Dr. V says DON'T DO IT]
f.. Androgens [Spontaneous remission, which happens more often to teen boys, so maybe male hormones can
help. It has BAD side effects to the liver, but no other long term side effects.]
g.. Other
Treatment Results: 79% are steroid responsive, 17% steroid non-responsive, 4% never tried steroids. Currently
37% of the DBAR patients are on steroid therapy, 31% on chronic transfusions. Of the transfusers, 35% have
never responded steroids, 22% are steroid refractory [I think that means they quit responding], 33% responded
but couldn't be weaned, 5% never tried steroids, and 5% unknown. 6% of the DBAR patients have had stem cell
transplants or other treatments (Reglan, Cyclosporin), 16% are in remission, and 10% are dead.
Side effects of steroids: 48% Cushingoid features, 22% pathologic fractures, 12% cataracts. Other side effects
are osteopenia without fracture, pseudotumor cerebrii [the brain acts like it has a tumor], diabetes mellitus,
hypertension.
