Scientific correspondence
`
`767
`
`0
`
`200
`
`600
`400
`PSC-Halghl
`
`Or.iad % Galed
`UL
`0.24
`UR
`<J.44
`LL
`9.a.n
`LR
`0.54
`
`~tid
`
`c.-
`
`:-
`
`.
`
`~10°10 1 ··~0J104
`
`-cD22RTC
`
`Quad % Ga1ed
`UL
`:2.32
`L~
`0-~~
`LL
`7D_a4
`ll=l
`26.51
`
`Ji'~]
`"~ 1 o 1 o:,:-: o2 10~ 104
`
`R...1-Hiilgh1
`Ou~d % Grat~c:l
`Ul
`5.7B
`u=!
`O.IB
`LL
`93.9~
`LR
`D.De
`
`Qu;,u:f %Gated
`UL
`3.07
`LFI
`:<!7_Q7
`Ll
`67.45
`LR
`1.!51
`
`~i..J
`
`:
`;:;;..-
`-<o
`S!10\l1a1 1~ 10 w4
`
`m3s~nc
`QLiad %G01!e-d
`Ul
`2B.50
`10 . .2g
`u;;j
`LL
`10.37
`LR
`50 . .!!3
`
`~~~'"-~.,I
`
`~" 101.10
`
`'" •o'
`FL1·f--l.eight
`O<Jad % Bat~d
`Lt
`.30.14
`UR
`l!_OE!
`Ll
`fi~JI
`L.FI
`0 06
`
`~[I
`
`..... '1 ~ ·-- .•.
`0~
`~ 11J 0 101 102 103 N 4
`CD7 FITC
`
`01JM %.Gated
`Ul
`0.02
`LH
`0.12
`LL
`9A..BO
`LR
`5.0S.
`
`Figure 1. Light scatter properties of analyzed cells (top).
`The flow cytometric dot plots clearly show that virtually all
`CD19• cells are positive for CD5 antigen and there are two
`cell populations with different HLA-DR antigen expression
`pattern. CD33 antigen is found to be the only antigen that
`expressed more than 50% of the cells and most of them are
`negative for HLA-DR antigen.
`
`nosisbut wedo not haveanydoubtsabout the diag(cid:173)
`nosis because more then 1 Ox 1 09/L cells expressa::l
`CDS, CD19, CD20 and CD22 (Rgure1).
`The concomitant presentation of AM Land CLL is
`extremely rare and the use of two-color flow cytom(cid:173)
`etry to differentiate the cell populations demon(cid:173)
`strates the utility of this technology in the diagnosis
`of unusual hematologic malignancies.
`llillsl:afa NJri 'renerel,* Ibrahim f-'ateni,' f-tiseyin l<eskin*
`* lstanbull..hi\.ersity, Istanbul 1\/edical &h:Jol, cepartment of Inter(cid:173)
`nal 1\/edicine, Dvision of rematology, <;apa, Istanbul; o Haseki
`State f-bspital, Haseki, Istanbul, Turkey
`
`Key words
`ca., AML, fiONq.t()l"fftry.
`Correspondence
`MLHafa Nuri Yenffa, MD, lganbul Uni\ffsty, lganbul
`Me::lirnl S:tlod, D~rn:nt of lntffnal Ma::lidne, Di\ison
`cf Hanatdq:y, 9JJE, lganbul, Turkey. Fax inta-national
`+90.212.6311263.
`
`References
`
`1. Caballero MD, Gonzalez M, Canizo MC, Orfao A,
`Nieto M~ San-Miguel ,.F Concomitant chronic lym(cid:173)
`phocytic lrukemia ( CLL) and acute myeloid lrukemia.
`Complete remission of CLL achieved with high-dose
`cytosine arabinoside. Lrukemia 1992; 6:856-8.
`2. Conlan MG, Mosher OF Concomitant chronic lym(cid:173)
`phocytic leukemia, acute myeloid leukemia, and
`thrombosiswith protein C deficiency. Case report and
`review of the literature. Cancer 1989; 63:1398-401.
`3. Rai KR, Patel DV. Chronic lymphocytic lrukemia. In
`Hoffman R, Benz EJ J", Slattil s.j Furie B, Cohen H~
`Silberstein LE(eds): Hematology BasicPrinciplesand
`Clinical Practice. 2nd ed. Curchill Livingstone, New
`York, 1995, p 1308.
`4. Lima M, Porto B, Rodrigues M, et al. Cytogenetic find(cid:173)
`ings in a patient presenting simultaneouslywith chron(cid:173)
`ic lymphocytic lrukemia and acute myeloid leukemia.
`Cancer-Genet Cytogenet 1996; 87:38-40.
`5. M ateu R, Bellido M, &ired a A, et al. Concomitant
`chronic lymphocytic leukemia and acute myeloid
`lrukemiawith an uncommon immunophenotype. Am
`JHematol1997; 56:281 .
`6. Tamul KR, Meyers DC, BentleySL\ Folds.D. Two col(cid:173)
`or flow cytometric analysis of concomitant acute
`myeloid lrukemia and chronic lymphocytic lrukemia.
`Cytometry 1994; 18:30-4.
`
`Pcute rn:galoblast i c anemia: horrocysteine
`le\els are useful for diagnosis ard fdlcw-up
`
`Sr,
`Vitamin ~2 (cobalamin) and folic acid deficiencies
`lead to megaloblastic anemia (MA), and induce
`accumulation of methylmalonic acid (MMA) and
`homocysteine (HG'r) .1 The most common presenta(cid:173)
`tion of MA isdassical macrocytic anemia. Other pre(cid:173)
`sentations are acute megaloblastosis (AM) and
`maskoo megaloblastosis. 2·3 1n this report, we present
`a case of AM diagnosa:l and followoo up by evalua(cid:173)
`tion of HCYievels.
`A 45-year old male was diagnosa:l as ha\1ng
`Rliladelphia-positive chronic myelogenous leukemia.
`Three years after diagnosis the patient developoo a
`lymphoid blast crisis and was start a:! on a chemo(cid:173)
`therapy protocol. The first consolidation treatment
`consist a:! of 6-mercaptopurine, methotre~te (MTX),
`\A\11-26 and cytarabine. MTX rescue with folinic acid
`was performoo following standard guidElines. On day
`+14 a platelet count of 9x1 09/L was found. Hb was
`99 giL, mean corpuscular VGiume (MC\1) 92 fl and
`leukocyte count was 7.06x109/L with 84%of neu(cid:173)
`trophilswith hypersegmentation. Reticulocyte count
`was 0.053x 1012/ L (1.66°~. Vitamin ~2 levels and
`roo cell folate were 322 pmol I L (normal 150-1200)
`and 938 nmoi/L(normal441-1285), respectively. A
`BM aspirate revealed 30% of erythroid precursors
`with megaloblastic features and a 55% of myeloid
`precursors with increased size and no blast cells.
`~rum HCYievelswere381Jmoi/L(normal < 16). The
`
`Haell)atologica vol. 84(8):August 1999
`
`NEPTUNE GENERICS 1020- 00001
`APOTEX 1020 - 0001
`
`

`
`768
`
`Scientific correspondence
`
`Table 1. Evolution of analytical parameters during folinic
`acid and vitamin B12 treatment.
`
`A"e-treatrnent 01set R:Jst -treat rnent
`Day -f)
`Day 0
`Day +9
`
`Ratelets (x1 09/ L.)
`Leukocytes (x1 09/ L.)
`1-emoglobin (gi L.)
`IVIOJ(fl.)
`R:!ticulocytes (x1 012/ L.)
`f-bm:x:yS:eine (IJTOI/ L.)
`
`134
`6.76
`91
`93
`0.037
`
`9
`706
`99
`92
`0.053
`38
`
`112
`5.72
`95
`95.3
`0.163
`9
`
`PM, acute rregaloblastosis; 11101, mean corpuscular volume.
`
`patient was diagnosed as having AM and began
`treatment with folinic acid 12 mg ivin onesingledose
`and folic acid 5 mg/day po for 14 days and par(cid:173)
`enteral vitamin ~2 2 mg/ day for 4 consecutive days.
`After 10 days of treatment the platelet count
`increased to 112x109/L and reticulocyte count to
`0.163x1012/L (5.41°/cy. Vitamin 812 level was 716
`pmoi/L, roo cell folatelevel1 ,506 nmoi/Land serum
`HCY level decreased to normal value (9 IJmoi/L)
`(Table 1).
`Four different dinical forms of megaloblastosis
`have been describoo. 3·4 The classical form has an
`insidious onset with frequent neurologic symptoms
`and macrocytic anemia. Vitamin ~2 and/ or roo cell
`folate levels are decreased. The second form is the
`subtle MA anemia with ill-definoo clinical symptoms
`and decreasa::l or borderline vitamin 812 and folic acid
`levels with other abnormalities(dUSf, HCY, MMA).2
`Maskoo megaloblastosis coexists with other defi(cid:173)
`ciencies; M CVis normal or decreasa::l .5·6 MA of acute
`onset is the rarest form. 3 There are two clinical pre(cid:173)
`sentations; the maskoo undiagnosed classical MA
`with cytopenias of abrupt onset and the so-calla::!
`AM .3-7 1n AM se\erethrombocytopenia de\elops in 1
`to 3 weeks, MCV is normal or only moderately
`increased. This presentat ion is more frequent in
`patients with risk factors: parenteral nutrition, infec(cid:173)
`tion, dialysis or treatment with someantifolatedrugs.
`Mortality is high. 3 The reticulocyte count is low. Vit(cid:173)
`amin ~2 and roo cell folate levels are normal. 8M
`aspirate shows megaloblastic changes. Classically,
`dUSf is used as a diagnostic test. Ne\ertheless, HCY
`serum assays provide a sensiti\€ test for the diagno(cid:173)
`sis of AM, especially in itsearlystages.8 1n vitamin ~2
`deficiences both HCY and M MA le\els are high. In
`
`is
`folate deficiencies only HCY concentration
`increa500_9,1o HCYievelsarealso useful for AM follow(cid:173)
`up of AM; le\els return to normal after starting treat(cid:173)
`ment with vitamin ~2 or folic acid. The evaluation of
`serum HCYievelsisan easy and non-invasi\etest for
`the diagnosis and follow-up of AM.
`
`Marina Carrasco, Pf1gel R=rracha, Alna &lreda,
`Alar Sarda, Rldrig:J Martino, JJrge Sierra.
`
`[Spartrnent of rerratology, f-bspital de Ia Santa O"eu i Sant Pau,
`Barcelona, Spain.
`
`Keywords
`Arutern:glloblacta:i~ faicacid, mbalarrin, hOTO<¥tEine
`Correspondence
`Ang3 Reracha SMIIa, MD, LaboratoriodeHaratdo;ja,
`Haptal dela Slnta Crru i 3lnt Pau, Antoni Maria i Claret,
`167, 08025 BarcElona, ~n. Phone: intffnational +34-
`93-2919290- Fax intffnational +34-93-2919192- E(cid:173)
`rrail: 2107@1~psantJEU.ES
`
`References
`
`1. Green R. Metabolite assay in cobalamin and folate
`deficiency. Bailliere Clin Haematol 1995; 8:533-66.
`2. Carmel R. SJbtle cobalamin deficiency. Ann Intern
`Med 1996; 124:338-40.
`3. RemachaA GmferrerE Lasmegaloblasl:osisagudas:
`revision y reconsideraci6n conceptual de las distintas
`formas de presentaci6n de las megaloblastosis. Bioi
`Clin Hematol1984; 6:167-82.
`4. Carmel R. Pernicious anemia. The expected findings of
`very low serum cobalamin levels, anemia, and macro(cid:173)
`cytosis are often lacking. Arch Intern Med 1988;
`148:1712-4.
`5. SpivakJ.... Masked megaloblastic anemia. Arch Intern
`Med 1982; 142:2111-4.
`6. Bennett M, Koren A, Ludacer E B12 deficiency in a(cid:173)
`thalassemia. N Engl JMed 1984; 310:1058-9.
`7. MartinezE, RemachaA Roca-CusachsA Acute exac(cid:173)
`erbation of folate-dependent chronic megaloblasl:osis.
`Bioi Clin Hematol. 1992; 14:223-9.
`8. Vester B, Rasmussen K High performance liquid chro(cid:173)
`matography method for rapid and accurate determi(cid:173)
`nation of homocysteine in plasma and serum. Eur J
`Clin Chem Clin Biocherm. 1991; 29:549-54.
`9. Allen RH, S:abler~, SavageDG, LindenbaumJ Diag(cid:173)
`nosis of cobalamin deficiency: I usefulness of serum
`methyl malonic acid and total homocysteine concen(cid:173)
`trations. Am JHematol 1990; 34: 90-8
`10. Lindenbaum~ S3vageDG, S:abler~. Allen RH. Diag(cid:173)
`nosis of cobalamin deficiency II: relative sensitivities
`of serum cobalamin, methylmalonic acid and total
`homocysteine concentrations. Am J Hematol 1990;
`34:99-107.
`
`Haell)atolo~ica vol. 84(8):August 1999
`
`NEPTUNE GENERICS 1020- 00002
`APOTEX 1 020 - 0002