Scientific correspondence
`
`767
`
`References
`
`1. Caballero MD, Gonzalez M, Canizo MC, Orfao A,
`Nieto MJ, San-Miguel JF. Concomitant chronic lym-
`phocytic leukemia (CLL) and acute myeloid leukemia.
`Complete remission of CLL achieved with high-dose
`cytosine arabinoside. Leukemia 1992; 6:856-8.
`2. Conlan MG, Mosher DF. Concomitant chronic lym-
`phocytic leukemia, acute myeloid leukemia, and
`thrombosis with protein C deficiency. Case report and
`review of the literature. Cancer 1989; 63:1398-401.
`3. Rai KR, Patel DV. Chronic lymphocytic leukemia. In
`Hoffman R, Benz EJ. Jr, Shattil SJ, Furie B, Cohen HJ,
`Silberstein LE (eds): Hematology: Basic Principles and
`Clinical Practice. 2nd ed. Curchill Livingstone, New
`York, 1995, p 1308.
`4. Lima M, Porto B, Rodrigues M, et al. Cytogenetic find-
`ings in a patient presenting simultaneously with chron-
`ic lymphocytic leukemia and acute myeloid leukemia.
`Cancer-Genet Cytogenet 1996; 87:38-40.
`5. Mateu R, Bellido M, Sureda A, et al. Concomitant
`chronic lymphocytic leukemia and acute myeloid
`leukemia with an uncommon immunophenotype. Am
`J Hematol 1997; 56:281.
`6. Tamul KR, Meyers DC, Bentley SA, Folds JD. Two col-
`or flow cytometric analysis of concomitant acute
`myeloid leukemia and chronic lymphocytic leukemia.
`Cytometry 1994; 18:30-4.
`
`Acute megaloblastic anemia: homocysteine
`levels are useful for diagnosis and follow-up
`
`Sir,
`Vitamin B12 (cobalamin) and folic acid deficiencies
`lead to megaloblastic anemia (MA), and induce
`accumulation of methylmalonic acid (MMA) and
`homocysteine (HCY).1 The most common presenta-
`tion of MA is classical macrocytic anemia. Other pre-
`sentations are acute megaloblastosis (AM) and
`masked megaloblastosis.2,3 In this report, we present
`a case of AM diagnosed and followed up by evalua-
`tion of HCY levels.
`A 45-year old male was diagnosed as having
`Philadelphia-positive chronic myelogenous leukemia.
`Three years after diagnosis the patient developed a
`lymphoid blast crisis and was started on a chemo-
`therapy protocol. The first consolidation treatment
`consisted of 6-mercaptopurine, methotrexate (MTX),
`VM-26 and cytarabine. MTX rescue with folinic acid
`was performed following standard guidelines. On day
`+14 a platelet count of 93109/L was found. Hb was
`99 g/L, mean corpuscular volume (MCV) 92 fL and
`leukocyte count was 7.063109/L with 84% of neu-
`trophils with hypersegmentation. Reticulocyte count
`was 0.05331012/L (1.66%). Vitamin B12 levels and
`red cell folate were 322 pmol /L (normal 150-1200)
`and 938 nmol/L (normal 441-1285), 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.
`Serum HCY levels were 38 µmol/L (normal < 16). The
`
`Haematologica vol. 84(8):August 1999
`
`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.
`
`nosis but we do not have any doubts about the diag-
`nosis because more then 103109/L cells expressed
`CD5, CD19, CD20 and CD22 (Figure 1).
`The concomitant presentation of AML and CLL is
`extremely rare and the use of two-color flow cytom-
`etry to differentiate the cell populations demon-
`strates the utility of this technology in the diagnosis
`of unusual hematologic malignancies.
`Mustafa Nuri Yenerel,* Ibrahim Hatemi,° Hüseyin Keskin*
`
`*Istanbul University, Istanbul Medical School, Department of Inter-
`nal Medicine, Division of Hematology, Çapa, Istanbul; °Haseki
`State Hospital, Haseki, Istanbul, Turkey
`
`Key words
`CCL, AML, flow cytometry.
`Correspondence
`Mustafa Nuri Yenerel, MD, Istanbul University, Istanbul
`Medical School, Department of Internal Medicine, Division
`of Hematology, Çapa, Istanbul, Turkey. Fax: international
`+90.212.6311263.
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`768
`
`Scientific correspondence
`
`Table 1. Evolution of analytical parameters during folinic
`acid and vitamin B12 treatment.
`
`Pre-treatment Onset
`Day –9
`Day 0
`
`Post-treatment
`Day +9
`
`Platelets (x109/L)
`Leukocytes (x109/L)
`Hemoglobin (g/L)
`MCV (fL)
`Reticulocytes (x1012/L)
`Homocysteine (µmol/L)
`
`134
`6.76
`91
`93
`0.037
`–
`
`9
`7.06
`99
`92
`0.053
`38
`
`112
`5.72
`95
`95.3
`0.163
`9
`
`AM, acute megaloblastosis; MCV, mean corpuscular volume.
`
`patient was diagnosed as having AM and began
`treatment with folinic acid 12 mg iv in one single dose
`and folic acid 5 mg/day po for 14 days and par-
`enteral vitamin B12 2 mg/day for 4 consecutive days.
`After 10 days of treatment the platelet count
`increased to 1123109/L and reticulocyte count to
`0.16331012/L (5.41%). Vitamin B12 level was 716
`pmol/L, red cell folate level 1,506 nmol/L and serum
`HCY level decreased to normal value (9 µmol/L)
`(Table 1).
`Four different clinical forms of megaloblastosis
`have been described.3,4 The classical form has an
`insidious onset with frequent neurologic symptoms
`and macrocytic anemia. Vitamin B12 and/or red cell
`folate levels are decreased. The second form is the
`subtle MA anemia with ill-defined clinical symptoms
`and decreased or borderline vitamin B12 and folic acid
`levels with other abnormalities (dUST, HCY, MMA).2
`Masked megaloblastosis coexists with other defi-
`ciencies; MCV is normal or decreased.5,6 MA of acute
`onset is the rarest form.3 There are two clinical pre-
`sentations; the masked undiagnosed classical MA
`with cytopenias of abrupt onset and the so-called
`AM.3-7 In AM severe thrombocytopenia develops in 1
`to 3 weeks, MCV is normal or only moderately
`increased. This presentation is more frequent in
`patients with risk factors: parenteral nutrition, infec-
`tion, dialysis or treatment with some antifolate drugs.
`Mortality is high.3 The reticulocyte count is low. Vit-
`amin B12 and red cell folate levels are normal. BM
`aspirate shows megaloblastic changes. Classically,
`dUST is used as a diagnostic test. Nevertheless, HCY
`serum assays provide a sensitive test for the diagno-
`sis of AM, especially in its early stages.8 In vitamin B12
`deficiences both HCY and MMA levels are high. In
`
`is
`folate deficiencies only HCY concentration
`increased.9,10 HCY levels are also useful for AM follow-
`up of AM; levels return to normal after starting treat-
`ment with vitamin B12 or folic acid. The evaluation of
`serum HCY levels is an easy and non-invasive test for
`the diagnosis and follow-up of AM.
`Marina Carrasco, Angel Remacha, Anna Sureda,
`Pilar Sardà, Rodrigo Martino, Jorge Sierra.
`
`Department of Hematology, Hospital de la Santa Creu i Sant Pau,
`Barcelona, Spain.
`
`Key words
`Acute megaloblastosis, folic acid, cobalamin, homocysteine
`Correspondence
`Angel Remacha Sevilla, MD, Laboratorio de Hematología,
`Hospital de la Santa Creu i Sant Pau, Antoni Maria i Claret,
`167, 08025 Barcelona, Spain. Phone: international +34-
`93-2919290 – Fax: international +34-93-2919192 – E-
`mail: 2107@hsp.santpau.es
`
`References
`
`1. Green R. Metabolite assay in cobalamin and folate
`deficiency. Bailliére Clin Haematol 1995; 8:533-66.
`2. Carmel R. Subtle cobalamin deficiency. Ann Intern
`Med 1996; 124:338-40.
`3. Remacha A, Gimferrer E. Las megaloblastosis agudas:
`revisión y reconsideración conceptual de las distintas
`formas de presentación de las megaloblastosis. Biol
`Clin Hematol 1984; 6:167-82.
`4. Carmel R. Pernicious anemia. The expected findings of
`very low serum cobalamin levels, anemia, and macro-
`cytosis are often lacking. Arch Intern Med 1988;
`148:1712-4.
`5. Spivak JL. Masked megaloblastic anemia. Arch Intern
`Med 1982; 142:2111-4.
`6. Bennett M, Koren A, Ludacer E. B12 deficiency in a-
`thalassemia. N Engl J Med 1984; 310:1058-9.
`7. Martinez E, Remacha A, Roca-Cusachs A. Acute exac-
`erbation of folate-dependent chronic megaloblastosis.
`Biol Clin Hematol. 1992; 14:223-9.
`8. Vester B, Rasmussen K. High performance liquid chro-
`matography method for rapid and accurate determi-
`nation of homocysteine in plasma and serum. Eur J
`Clin Chem Clin Biocherm. 1991; 29:549-54.
`9. Allen RH, Stabler SP, Savage DG, Lindenbaum J. Diag-
`nosis of cobalamin deficiency: I: usefulness of serum
`methylmalonic acid and total homocysteine concen-
`trations. Am J Hematol 1990; 34: 90-8
`10. Lindenbaum J, Savage DG, Stabler SP, Allen RH. Diag-
`nosis of cobalamin deficiency: II: relative sensitivities
`of serum cobalamin, methylmalonic acid and total
`homocysteine concentrations. Am J Hematol 1990;
`34:99-107.
`
`Haematologica vol. 84(8):August 1999
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