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SUMMARY
Daniil Valerievich VELICHKO, born January 15, 2001
Address: ul. Krupskoi 19-29, Yalta, Crimea, Ukraine
Clinical diagnosis: 1. Retroperitoneal neuroblastoma stage 3 (2002). 2. Secondary acute myeloid leukemia (M1 – FAB), early-stage differentiation with monosomy 7 (June 12, 2007).
Consequences of the removal of neuroblastoma (extra-, intraventricular, and extradural localization) at the level of Th12-L2 with slight paresis of legs and minor functional pelvic disorder.
Chronic viral hepatitis C of minimum activity.
Blood group B(III) Rh(pos)
Diagnostic summary:
The child received treatment for retroperitoneal neuroblastoma since 2002. The chemotherapy was completed on March 3, 2004. Remission, regular monitoring. Changes in the CBC were revealed during a check-up on June 12, 2007. According to the results of the bone marrow examination and immunophenotypic study of blast cells, the child was diagnosed with acute biphenotypic leukemia. Consulted by Dr. S.B. Donskaya, Chief Child Hematologist of Ukraine. Decision: the only radical treatment method possible in this case is unrelated marrow transplantation somewhere outside Ukraine.
The child was admitted to the Center for Child Oncology and Hematology on July 5, 2007, in grave but stable condition. No fever. Hemorrhagic rash on the trunk and limbs. Slight mucositis. Lymph nodes of all groups enlarged up to 1.5 cm. Enteral uptake. Stable hemodynamics. Lungs without alterations. Liver +3.0 cm, spleen +2.0 cm.
CBC on admission: Hb 103 g/L, RBC 3.31 x 1012/L, PLT 56 x 103, WBC 22.4 x 103/L, blasts 10%, juven 2%, bands 5%, segm 18%, lym 25%, mon 40%.
Blood biochemistry test on admission: within normal ranges for the boy’s age.
Bone marrow examination No. 930/07 of July 6, 2007: blast cells 32.5%, M1 – FAB, myelokaryocytes 250, megakaryocytes 0.012. Bone marrow punctate rich in cellular elements. Low content of megakaryocytes; some are functioning. Low content of platelets.
Cytochemical study of blast cells: peroxidase reaction positive for 7% blasts, lipid reaction positive for 12% blasts, glycogen (in diffuse and fine-granular forms) reaction positive for 14% blasts.
Immunophenotypic assay of blast cells: early myeloid leukemia with CD 22+ and CD 10+ coexpression.
Cytogenetic study of blast cells: 45 XY, -7 (minus 7th chromosome)
Molecular biology of blast cells: no prognostically significant rearrangements found.
CSF test on admission: no pathological signs found.
Heart ultrasound on admission: LV cavity somewhat dilated. Valve functioning normal. Total contractility of LV myocardium satisfactory. LV 39 mm, RV 12 mm, heart rate 83 bpm, SF 35%, EF 65%, CO 3.5 L/min.
Abdominal ultrasound on admission: Liver (+3 cm) and spleen (+3.5 cm) enlarged. Diffuse alterations of liver and kidney. Multiple lymph nodes near the hepatic porta and in the projection of the pancreas up to 14 mm. Ultrasound evidence for gallbladder hypotonia.
Chest X-ray No. 4040 of July 9, 2007: No pathological alterations.
Blood test of July 5, 2007: HBsAg negative, a/HCV positive.
Blood test for HCV RNA of July 9, 2007: observed amount 2.55x105 IU/mL.
Blood test of July 18, 2007: CMV IgM negative, CMV IgG positive, HSV IgM negative, EBV IgM positive.
Blood test of July 9, 2007: Ag Aspergillus negative, At Aspergillus IgM negative, At Aspergillus IgA/G positive.
Treatment according to AML-MM-2003 protocol since July 10, 2007. Total doses of cytostatics:
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ADE-HAM
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July 10 to 27, 2007
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ARA-C
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4 212 mg
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Vp
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405 mg
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MIT
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16.2 mg
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ARA-C e/l
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40 mg
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40 mg
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From July 10 to 16, 2007, ADE.
Early toxicity 3-4 (WHO). Complete infusion, supplementary, transfusion, antibacterial, antifungal, antiviral therapy. Complications: cytopenic syndrome, toxic keratitis. Consulted by an ophthalmologist; therapy as recommended.
July 26 to 27, 2007: the second part of HAM induction (in view of toxic keratitis in the anamnesis, Cytosar produced by another company was used).
For further treatment, in view of deep cytopenic syndrome, the child was transferred to the Department of Marrow Transplantation by agreement with Yu.S. Strongin, Head of Department.
Treatment at the Department of Marrow Transplantation from July 27 to August 23, 2007.
Cytopenia July 20 to August 19, 2007 (31 days).
Treatment: decontamination, Augmentin IV, Fungizone IV, Heptral IV, Ursosan per os, Neuromedin per os, Immunoglobulin IV, Etamsylate IV, replacement therapy with blood components according to indications (last transfusion of leukocyte- and platelet-depleted RBCs B(III)Rh(pos) on August 17, 2007; last platelet transfusion on August 20, 2007).
Discharged from hospital in compensated condition.
· CBC of August 23, 2007: Hb 84 g/L, RBC 3.3x109/mL, PLT 55x103/L, WBC 1x103/L.
· Blood biochemistry test of August 23, 2007: CRP < 0.5 mg/mL, ALT 122 MU/L, AST 53 MU/L, GGT 38.8 MU/L
Received treatment on day-patient basis on August 24 to 27, 2007
Next admission to the Department of Marrow Transplantation on August 27, 2007
Presently the child is at the Department of Marrow Transplantation in stable condition. No fever. Child is active. Skin and mucous membranes are pale pink, with moderate hemorrhagic syndrome. Pulm without pathological alterations. Stable hemodynamics. Liver +1.5–2 cm; spleen +0.5 cm.
· Bone marrow test No. 1172/07 of August 28, 2007: blasts 30%, myelokaryocytes 93x103/L, megakaryocytes 0.006x103/L, erythrokaryocytes 19.5%, neutrophils 20%, eosinophils 0.5%, lymphocytes 24.25%, monocytes 5.5%, plasma cells 0.25%. Bone marrow punctate rich in cellular elements. Low content of megakaryocytes; functioning ones not found. Low content of platelets.
· MTT test of August 31, 2007: under processing.
· CBC of August 30, 2007: Hb 91 g/L, RBC 3.34x109/mL, PLT 24x103/L, WBC 1.1x103/L, eos 2%, segm 12%, lym 40%, mon 46%.
The child’s condition and treatment have been discussed with Prof. O.V. Aleinikova, Director of Center. Considering the diagnosis (AML with early-stage differentiation and monosomy 7) and the absence of remission after the induction therapy (ADE-HAM cycle), the tactics of further therapy will be determined according to the results of the MTT test.
August 31, 2007
Physycian Yu.E. Mareiko
Head of the Department of Marrow Transplantation Yu.S. Strongin
Deputy Director of Hospital O.N. Romanova
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MINISTRY OF PUBLIC HEALTH
REPUBLIC OF BELARUS
REPUBLICAN SCIENTIFIC AND PRACTICAL CENTER FOR HEMATOLOGY AND TRANSFUSIOLOGY
Laboratory of Organ and Tissue Immunological Typing
Dolginovskii tr. 160, Minsk, 223059 Belarus; phone 289-8586
July 10, 2007
No. 429
Material received from:
Republican Scientific and Practical Center
for Child Oncology and Hematology
Results of donor-recipient matching for marrow transplantation
I. Determination of HLA phenotype (blood samples):
D. Velichko (rec.): A2,28 B49,51 Cw7 Bw4
L.R. HLA DRB1*12,15; DQB1*03,06; DRB3*; DRB5
H.R. HLA DRB1*120101, 1501; DQB1*0301, 0602
2. N.N. Velichko (mother): A1,28 B13,51 Cw6 Bw4
3. V.Yu. Velichko (father): A2,24 B44,49 Cw7 Bw4
II. Cross-match reaction between the recipient’s serum and the donor lymphocytes_____
between the donor’s serum and the recipient’s lymphocytes________________________
III. Decision: according to the data of HLA type determinations_____________________
Laboratory physician S.V. Semenova
Head of Laboratory T.V. Semenova
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Study of Blast Cell Susceptibility to Chemotherapy Drugs (MTT test)
Patient: D.V. Velichko
Material taken on August 31, 2007
Material studied on August 31, 2007
Drugs
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Concentration range studied
(mg/mL)
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Semilethal concentrations
(LC 50, mg/mL)
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Dexamethason
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0.0002–6.0
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0.02
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Prednisolon
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0.008–250.0
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0.22
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Vincristine
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0.05–50.0
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0.45
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L-asparaginase
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0.003–10
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1.75
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Rubomycinum
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0.008–8.0
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0.055
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Doxorubicin
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0.008–8.0
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0.11
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Vepesid
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0.05–50.0
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50.0
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Conclusion: The patient’s blast cells are not susceptible to Vepesid.
The susceptibility of the patient’s blast cells to Dexamethason and L-asparaginase is reduced. The leukemic cells are susceptible to Rubomycinum, Doxorubicin, Vincristine, and Prednisolon.
September 5, 2007
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DKMS Life Science Lab GmbH * Fiedlerstr. 34 * 01307 Dresden
Director
Univ.-Prof. Dr. med. Ralf Waßmuth
Address
DKMS Life Science Lab GmbH
Fiedlerstr. 34
01307 Dresden
Dr. rer. nat. Monika Füssel
Sucheinheit Dresden und
Klinisches HLA Labor
Telefon 0351 / 4450 4553
Telefax 0351 / 450 4545
E-mail
fuessel@dkms-lab.de
Dresden, July 20, 2007
HLA-typing Labor – No: R26181
AVS-Material-No: M0024796
Velichko, Daniil born January 15, 2001
Order: Confirmatory Typing before the beginning of search for an unrelated donor
Material taken on: July 18, 2007 Material delivered on: July, 19, 2007
Method: molecular genetic study (PCR-SSP)
HLA-A*0201, *6801; HLA-B*4901, *5101; HLA-Cw*0701, *1502
HLA-DRB1*120101, *1501; HLA-DQB1*0301, *0602
Locus HLA-A contains ambiguities
The following allele combinations are possible: HLA-A*0295, *6801 and HLA-A*0297, *6801.
Locus HLA-В contains an ambiguity.
The following allele combination is possible: HLA-В*4901 *5118
Conclusion:
Repeated typing of patient Daniil Velichko according to the second independent blood test confirms and supplements the expert conclusion made in Minsk.
Dr. rer. nat. M. Füssel Prof. Dr. med. K.-H. Frank Univ.-Prof. Dr. med. R. Waßmut
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