R.E. Kavetsky Institute of Experimental Pathology Oncology and Radiobiology of the National Academy of Sciences of Ukraine 

All-Ukrainian Charitable Foundation “Hematologists for Patients with Malignant Blood Disorders” 

Registration No. 49606 п/к; 49607 к/м

Clinic – Scientific Center of Radiation Medicine of the Academy of Medical Sciences of Ukraine Chernihiv region, Kulikovsky district, village of Drozdovka

Examined: blood and bone marrow smears.

Patient name, age – Dmitruk Tatiana Vladimirovna, born on May 20, 2001.

Morphology:

The patient has been already examined earlier (see No. 46406-407 dated November 21, 2008)

At present the patient has marked leucopenia. Leukogram detected 32% of blast cells of myeloid type.

In bone marrow: diffuse infiltration with monoblasts (97%), increased number of mitosis.

Peroxidase – the reaction is negative in most blasts and slightly positive in 8-10%.

Acid phosphatase – micro-granular reaction

Acid nonspecific esterase – strongly positive reaction

PAS – micro-granular reaction

Acute myeloblastic leukemia

(М5а acute myeloblastic leukemia according to FAB classification), relapse.

Chernigov Regional Children’s Hospital  

Pediatric department

Case record

of inpatient No. 6607

The patient was referred to the pediatric hematology department of Scientific Center of Radiation Medicine of the Academy of Medical Sciences of Ukraine

Name: Dmitruk Tatiana Vladimirovna

Patient age: born on May 12, 2001 Address: Chernihiv region, Kulikovsky district, village of Drozdovka, Gorkogo st. 73

Date of hospitalization: June 09, 2009 Date of discharge: July 17, 2009

Final diagnosis:

Acute myeloblastic leukemia,

М5а,

Second acute period,

cardiolemia НКо

Faint accommodation ОО

Consequence of haemorrhagic stroke - mild right-side pyramidal insufficiency

Complete blood count

Biochemical blood assay  

Proteinogram: total protein 62 g/l, 65 g/l

General urinalysis:

CSF analysis

ECG – mild abnormalities of ventricles’ repolarisation

EEG – corresponds to the age. Brain CT of May 15, 2009 – atrophied focus in left temporoparietal area.

Myelogram – dated July 15, 2009 – blasts – 97%, neutrophilic promyelocytes – 1%, neutrophilic myelocytes – 1%, polychromatonormocytes 1%

On July 16, 2009 the smears of bone marrow were sent to the laboratory of R.E. Kavetsky Institute of Experimental Pathology Oncology and Radiobiology

ENT (without pathology).

Oculist – faint accommodation ОО, fundus of eye is normal.

Cardiologist – cardiopathy, НКо.

Neuropathologist – consequences of haemorrhagic stroke - mild right-side pyramidal insufficiency

Therapy: biseptol 480, erespal, hepabene, thiotriazolinum, asparkan, lanvis, treniseptol intramuscularly;

LP with cytarabine administration of 40 mg №4, radiation therapy 18 Gy, subcutaneous granocyte– 33.6 million IU on July 10, 2009 and July 13, 2009

REGISTRATION CARD #7

Academy of Medical Sciences OF UKRAINE

STATE INSTITUTION "Scientific Center for Radiation Medicine"

CLINIC

Kiev, pr. Peremogy 119, 121

Department of Radiation Hematology for Children, tel.: 451-82-90

Case record of inpatient #1507

Name:           Dmitruk Tatiana Vladimirovna

AGE:               born on May 12, 2001

PLACE OF RESIDENCE: Chernihiv region, Kulikovsky district, village of Drozdovka, Gorkogo st, 50

DATE OF ADMISSION: November 26, 2008  DATE OF DISCHARGE: June 04, 2009

FINAL DIAGNOSIS:

Basic diagnosis: Acute myeloblastic leukemia, M5a, the first acute period, the patient entered the stage of clinical and hematologic remission since January 15, 2009.

Complications: Tumor lysis syndrome. Hepatic veno-occlusive disease. Interstitial peritonitis. Hematencephalon. Generalized vascular Bilateral lower lobe pneumonia disease. Retinal hemorrhage in both eyes.. Left-sided pleuropneumonia. Toxic cardiopathy. Toxic hepatitis.

Concomitant diseases: Retinal angiodystonia in both eyes. Maculopathy in the right eye.

The child was admitted to the department in grave condition (pale, intoxicated), with marked symptoms of anasarca, hyperplasia of peripheral lymph nodes, hepatosplenomegaly. 

Results of laboratory analyses

Blood group: A(II) Rh-positive blood

COMPLETE BLOOD COUNT:

biochemical blood assay: AT ADMISSION: total protein 55 g/l, glucose 4.4 mmol/l, total bilirubin 5.8 μmol/l, blood urea 6.5 mmol/l, creatinine 119.9 μmol/l, GPT 12 unit/l, GOT 37 unit/l. Alkaline phosphatase 155 μkat/l, LDH 1398.0 unit/l. Cholesterol 2.1 μmol/l, Albumins -48.2%, Globulins -51.8%, α1-globulin - 2.7%, α2-globulin - 12.8%, β-globulin - 10.3%, γ-globulin - 26.0%, protein index - 0.93. Creatine phosphokinase - 29 unit/l.

December 07, 2008 - total protein 50.8 г/л, total bilirubin 102.8 μmol/l, GPT 15.7 unit/l, GOT 17.2 unit/l.

December 28, 2008 - total protein 74.7 g/l, total bilirubin 17.9 μmol/l, GPT 14.2 unit/l, GOT 17,4 unit/l.

May 31, 2009 - total protein 63.4 g/l, glucose 5.3 mmol/l, total bilirubin 8.4 μmol/l, blood urea 3.3 mmol/l, creatinine 60.3 μmol/l, GPT 77.6 unit/l, GOT 43.1 unit/l.

myelogram: dated January 15, 2009: number of myelokariocytes – 100.0 g/l, blast cells – 1.6%, promyelocytes – 1.4%, myelocytes – 17.6%, immature – 5.6%, stab – 10.0%, segmented – 8.6% basophils – 0.2, eosinophils - 0%, lymphocytes 1.6%, monocytes - 11,0%, erythroblasts – 0.6%, normocytes: basophilic – 4.8%, polychromatophilic – 4.4%, oxyphilic -1.4%, total erythroid cells – 24.4%, megacaryocytes 5/10 per HPF, forms of mitosis – 0.2.

myelogram: dated February 17, 2009: number of myelocariocytes – 60.0 g/l, blast cells – 1.2%, promyelocytes – 0.6%, myelocytes – 6.2%, immature – 4.0%, stab – 10.0%, segmented – 10.0% basophils – 0.2, eosinophils – 0.2%, lymphocytes -15.2%, monocytes – 21.2%, erythroblasts – 0.4%, normocytes: basophilic – 1.8%, polychromatophilic – 8.2%, oxyphilic – 14.8%, total erythroid cells - 25.2%, megacaryocytes 5/10 per HPF.

myelogram: dated March 20, 2009: number of myelocariocytes – 160.0 g/l, blast cells – 1.0%, promyelocytes – 0.8%, myelocytes – 7.2%, immature – 4.8%, stab – 14.2%, segmented – 18.0% promonocytes14%, eosinophils – 0.4%, lymphocytes – 5.0%, monocytes - 7.6%, erythroblasts – 1.2%, normocytes: basophilic – 4.8%, polychromatophilic – 11.6%, oxyphilic – 22.0%, total erythroid cells – 39.6%, megacaryocytes 4/10 per HPF.

myelogram: dated April 30, 2009: number of myelocariocytes – 170.0 g/l, blast cells – 5.4%, promyelocytes – 1.6%, myelocytes – 8.2%, immature – 4.4%, stab – 13.4%, segmented – 17.4% basophils - 0%, eosinophils – 0.4%, lymphocytes - 16.8%, monocytes – 6.4%, erythroblasts – 1.6%, normocytes: basophilic – 1.6%, polychromatophilic – 6.4%, oxyphilic – 16.4%, all erythroid – 26.0%, megacaryocytes 2/10 per HPF.

myelogram: dated June 02, 2009: number of myelocariocytes – 130.0 g/l, blast cells – 1.4%, promyelocytes – 1.2%, myelocytes – 5.4%, immature – 2.0%, stab – 10.8%, segmented – 11.0% basophils - 0.6%, eosinophils - 0.2%, lymphocytes - 11.2%, monocytes – 7.8%, erythroblasts – 0.8%, normocytes: basophilic – 4.2%, polychromatophilic – 13.2%, oxyphilic - 30.4%, all erythroid – 48.6%, megacaryocytes 3/10 per HPF, forms of mitosis – 0.2.

DNA TESTING: Expression of BCR/ABL chimeric gene is not detected in the cells of bone marrow and peripheral blood.

Cytogenetic testing: Colonial karyotype abnormalities are not detected.

immunoassay: Ig - 1.78 g/l, IgG - 9.49 g/l, IgM - 0.92 g/l, circulating immune complex – 4.166% - 5 units of optical dense, circulating immune complex 7.2% - 90 units of optical dense.

anti-infective immunity: HBs AG – negative, RW – negative, anti-HCV – positive 26, anti CMV,  IgG – positive 4.26, anti-Toxo, IgG – negative, anti HSV, IgG – positive 1.77, Epstein-Barr virus NA IgG positive 2.47.

Bacteriological analysis of blood: bacteremia is not detected.

Bacteriological analysis of the pharynx and nose mucous membranes swabs:

pharynx – heavy increase of S.epidermidis, moderate increase of Str.viridans, moderate increase of Ent.Faecium.

Nose – microflora is not detected.

examination OF cerebrospinal fluid: dated December 04, 2009 transparent, cytosis 1.2 х3 mm³, dated December 11, 2008 cytosis 72х3 mm³ (RBC), protein 0.099 g/l, dated December 12, 2008 slightly turbid, protein 0.264 g/l, cytosis 8.4х3 mm³ , microscopy: invariable RBC, dated December 16, 2008 protein 0.165 g/l, cytosis 1.2 х1 mm³ , dated December 23, 2008 number 1.5 ml, transparent, protein 0.066 g/l, cytosis 4.8х3 mm³ , dated December 30, 2008 number 0.7, transparent, cytosis 6.6 х3 mm³ , protein 0.066 g/l, dated January 06, 2009 transparent, protein 0.099 g/l, cytosis 2.2х1 mm³ , dated January 15. 2009 slightly turbid, protein 0.066 g/l, cytosis 3.6х1 mm³ , dated January 25, 2009 transparent, protein 0.1 g/l, cytosis 3.9 х3 mm³ , dated February 21, 2009 transparent, protein 0.066 g/l, cytosis 2 х3 mm³ , dated May 05, 2009 cytosis 3.6 в 1 μl transparent, protein 0.099 g/l, от June 02, 2009 cytosis 1 in 1 μl transparent, protein 0.099 g/l.

Clinical urinalysis:  no changes.

Feces for egg/helminth: egg/helminth and protozoa are not detected.

RESULTS OF instrumental examination

ECG: Rhythm – sinus tachycardia, vertical position of the electrical heart axis, vertical electric position, systolic overloading of the left atrium, predominance of the left ventricle, abnormalities of myocardium repolarisation processes in the segment of posterior wall of the left ventricle.

Ultrasonic examination of the visceral organs: dated November 26, 2008. Liver: 124х51 mm, enlarged, tissue echogenicity retained, homogeneous structure, granular pattern, bile ducts are free, portal system is not dilated 7 mm. Gallbladder is enlarged, extended, folded in the lower third (67х20 mm), wall up to 2 mm. Pancreas: 23х13х20 mm, thickened, tissue echogenicity retained, the structure is heterogeneous because of the small hyperechoic segments, the border is even, no focal changes. Spleen: enlarged 156х56 mm, homogeneous, splenic vein is not dilated. The right kidney: 135х50 mm, parenchyma 17 mm, enlarged, echogenicity of parenchyma is moderately enlarged, hollow system is expanded. Pelvicalyceal system deformed, the left kidney: 119х43 mm, parenchyma 15 mm, is not enlarged, echogenicity of parenchyma is moderately enlarged, hollow system not expanded, Pelvicalyceal system deformed, single hyperechoic formations of 1 mm on both sides. In the area of small pelvis small amount of free liquid is visualized, in the left lower flange of the abdominal cavity free liquid is detected sized 46х16 mm.

Dated June 01, 2009 г. Liver: 117х40 mm, enlarged, tissue echogenicity is retained, homogeneous structure, granular pattern, bile ducts are free, portal system is not dilated 8 mm. Gallbladder is enlarged, folded in the neck  (68х13mm), the wall is up to 1- 2 mm. Pancreas: 23х12х29 mm, thickened, tissue echogenicity is retained, the structure is heterogeneous because of the small hyperechoic segments, the border is even, no focal changes. Spleen: is not enlarged 114х35 mm, homogeneous, splenic vein is not dilated. The right kidney: 104х32 mm, parenchyma 13 mm, the left kidney: 94х37 mm, parenchyma 16 mm, single hyperechoic formations of 1 mm on both sides.

thyroid gland ultrasound: is located in typical place, not enlarged, isthmus of gland is not thickened, capsule is not thickened, the border is even, echogenicity without changes, echostructure is homogeneous, right lobe is 43х8х13 mm, V – 2.14 cm³, left lobe is 41х9х13 mm, V- 2.29 cm³.

HEART ultrasound: aorta, aortic valve – moderately thickened. Mitral valveas are not changed. Cardiac chambers are not dilated. Hypertrophy of the left ventricle walls is not detected. Myocardium contractility is increased (ejection fraction – 67%). Exudate is absent.  Laparocentesis dated December 04, 2008. 1 liter of exudate is taken out.

CHEST X-RAY – dated December 10, 2008: the signs of the lower lobe pneumonia in the right, lower lobe pleuropneumonia in the left.

CHEST X-RAY – dated October 19, 2008: the signs of the bilateral lower lobe pneumonia, left-sided exudative pleurisy.

CHEST X-RAY – dated January 05, 2008: the signs of the bilateral lower lobe pneumonia in the stage of resolution.

CHEST X-RAY – dated February 25, 2009 – lung pattern in root areas is intensified because of the peribronchial component. Roots of lungs are anhistous, intensified at the expense of vascular component. Cardiovascular marking is not dilated.

Consultations

Cardioreumatologist – secondary cardiopathy.

                          Dentist – caries. Chronic periodontitis.

Ophthalmologist – dated February 24, 2009. Retinal hemorrhage in both eyes. Dated 03, 2009. Retinal angiodystonia in both eyes. Masculopathy in the right eye.

Received treatment: according to protocol BFM -2002 AML (. The stage of cytoreduction (hydroxyurea) started since November 26, 2008; therapy with cytosar 40 mg/m² daily since December 01, 2008, the therapy of AIE block started since December 03, 2008, HAM, AI, hAM, HAM blocks), antimicrobial, fungicide, antiviral therapy, haemostatic therapy, blood products transfusion: (packed red cells A (II) positive № 19, platelet concentrate № 32, fresh frozen plasma №6), infusion and symptomatic therapy.

RECOMMENDATIONS:

1.    Haematologist supervision at the place of residence.

2.    Dietotherapy, diet # 5.

3.    Control of complete blood count, biochemical blood assay.

4.    Brain CT with vascular enhancement.

5.    Brain irradiation (cumulative dose 18 Gy) with four intrathecal administrations of cytarabine   (days 1, 15, 21, 28 from the beginning of irradiation) simultaneously with supportive therapy: 6-thioguanine 40 mg/m² daily with four day blocks of cytarabine monthly (40 mg/m² in 24 hours subcutaneous).  Dose adjustment of 6-thioguanine: WBC level  > 3000/mm³ – 150%. >2000/mm³ – 100%, >1000/mm³ – 50%, <1000/mm³ – 0%.

6.    Ophthalmologist prescription – lutein-complex 1 tablet once daily for 2 month.

The patient has not been in contact with a contagious patient

ATTENDING DOCTOR                                                                                signature

(Gonchar L.O.)

CHIEF OF DEPARTMENT                                                                                      signature

(Kuznetsova O.E.)

DEPUTY HEAD DOCTOR                                                                           signature

(Kolos V.I.)

THE MINISTRY OF HEALTH OF UKRAINE

NATIONAL CHILDREN CLINICAL HOSPITAL “OHMATDYT”

01135, Kyiv                                                                                       tel.:+38-(044)-236-02-14

Chornovola str., 28/1                                                                         fax/tel.: +38-(044)-236-42-15

Sholudenko str., 10

September 26, 2009.

                                               CONSULTATIVE CONCLUSION

Patient: Dmytruk Tatyana Vladimirovna

DOB: May 12, 2001.

Home address: Kulikovsky Region, Chernigiv Oblast.

Diagnosis: acute myeloid leukemia (M5a – by the results of morpho-cytochemical examination). The Ist early bone marrow relapse.

Considering the relapse character, in case of complete or at least partial secondary remission the girl has an absolute indication for transplantation from unrelated HLA-compatible or partially compatible family donor abroad (outside of Ukraine).

Director of Center of Children Oncology, Hematology

and Bone Marrow Transplantation (DOG TKM Center)

Chief Children Hematologist

of the Ministry of Health of Ukraine                 (Signature)                               S. Donskaya

                                                                                  REGISTRATION CARD #7

Academy of Medical Sciences OF UKRAINE

STATE INSTITUTION "Scientific Center for Radiation Medicine"

CLINIC

Ukraine, Kiev, pr. Peremogy 119, 121

Department of Radiation Haematology for Children, tel.: +38 044 451 82 90

Case record of inpatient #911

Name:            Dmitruk Tatiana Vladimirovna

DOB:               May 12, 2001

PLACE OF RESIDENCE: Chernigov region, Kulikovsky district, village of Drozdovka, Gorkogo st, 50

DATE OF ADMISSION: July 17,  2008  DATE OF DISCHARGE: UP TO THE PRESENT MOMENT

FINAL DIAGNOSIS:

Main: Acute myeloblastic leukemia, M5a, bone-marrow recurrence.

Complications: myelosuppression of IV stage. Febrile neutropenia. Transient cholestasis. Right-sided lower lobe pneumonia.

Concomitant diseases: retinal angiodystonia of both eyes.

The child was admitted to the department in grave condition (pale, intoxicated), severe skin hemorrhagic syndrome, peripheric lymph nodes and spleen are not enlarged, liver is + 2.5 cm lower costal arch. After receiving FLAG-Mito anti-relapse course, the bone-marrow remission was not achieved.

LABORATORY REPORT

BLOOD GROUP: A(II) RH POSITIVE

COMPLETE BLOOD COUNT:

biochemical blood assay: Sept 01, 2009: total protein 66 g/l, glucose 3.8 mmol/l, total bilirubin 6.0 μmol/l, blood urea 3.8 mmol/l, creatinine 65.0 μmol/l, GPT 196 unit/l, GOT 50 unit/l, ALP 179 μkat/l.

bacterial examination OF BLOOD: bacteremia is not detected.

bacterial examination OF swab FROM throat AND NOSE mucous membrane:

Throat – microflora is not detected.

Nose – microflora is not detected.

examination OF cerebrospinal fluid: of Jjuly 17, 2009 – transparent, cytosis 3.7 x 3 mm³, protein 0.090 g/l.

General urinE alysis:  no changes. 

RESULTS OF instrumental examination

ECG: rate – sinus tachycardia, vertical position of the electrical axis of heart, vertical electric position, enlargement of left atrium, left ventricle with no abnormality, not evident myocardial changes, more evident in the posteroanterior wall of the left ventricle.

abdominal ultrasound: liver – 116 x 41 mm, enlarged, tissue echogenicity is retained, homogeneous structure, granular pattern, bile ducts are free, portal system is not dilated 7 mm. Gallbladder is enlarged, extended, folded in the neck (70 x 19 mm), the wall is up to 1 mm. Pancreas: 24 x 14 x 25 mm, thickened, tissue echogenicity is retained, the structure is heterogeneous because of the small hyperechoic segments in the tail segments, the border is even, no focal changes. Spleen: enlarged 135 x 54 mm, homogeneous, splenic vein is dilated 10 mm. The right kidney: 115 x 33 mm, parenchyma 15 mm, is not enlarged, echogenicity is retained, the left kidney: 111 x 36 mm, parenchyma 15 mm, is not enlarged, parenchyma echogenicity is retained, hollow system is not expanded, single hyperechoic formations of 1 mm on both sides.

HEART ultrasound: valves are not changed. Chambers of heart are not dilated. Hypertrophy of the left ventricle walls is not detected. Myocardium contractility is increased (ejection fraction – 62%). No effusion. Apical additional transversal chorda of the left ventricle.

CHEST X-RAY of August 07, 2009: signs of the right-sided lower lobe pneumonia.

Consultations

Surgeon – there are no signs of acute surgical pathology.

Neurologist – no pathology.

Ophthalmologist – retinal angiodystonia of both eyes.

THERAPY GIVEN: FLAG-Mito anti-relapse course, antimicrobial, fungicide, antiviral therapy, haemostatic therapy, blood products transfusion, fluid and supportive therapy.

The case record is given per mother’s request.  

ATTENDING DOCTOR [signature] (Gonchar L.O.)

DEPARTMENT CHIEF [signature] (Kuznetsova O.E.)

ASSISTANT HEAD DOCTOR [signature] (Kolos V.I.)

September 03, 2009

[Seal]

Ukraine, State Institution “Scientific Center for Radiation Medicine”

Academy of Medical Sciences OF UKRAINE

Identification code 048378335

Clinic

Academy of Medical science of Ukraine

Scientific centre of Radiation medicine

53 Melnikova street, Kiev, 25405, Ukraine

Phone 483 0637, 483 9215.

Fax 483 7202

Laboratory of immune genetics

July, 31, 2009

The results of molecular HLA – genotype

The molecular genetic research was conducted with SSP method

Birth certificate

Citizen of Ukraine

Dmuytruk Tetyana Volodymyrivna  was born May, 12, 2001.

The birthplace is Drozdivka village, Kulikovskyi region, Chernihiv district.

The act of birth was denoted under the number 4 on August, 2, 2001 in the Book of civil acts of birth statement.

Parents:

Father: Dmytruk Volodymyr Mykhaylovych, citizen of Ukraine

Mother: Maslova Iryna Volodymyrivna, citizen of Ukraine

Place of registration:

Executive Committee of Drozdiv village council, Kulikovskyi region, Chernihiv district.

Date of issue: September, 27, 2001