[Functional dyspepsia: a multifaceted problem in gastroenterology].

The article presents the views on dyspepsia in world practice, data on the difficulties of diagnosis and the problem of the effectiveness of various therapy regimens. Particular attention is paid to the use of fixed forms of drugs for functional dyspepsia, in particular Omez DSR.

Tracking T-cell immune reconstitution after TCRαß/CD19-depleted hematopoietic cells transplantation in children.

αßT-cell-depleted allogeneic hematopoietic cell transplantation holds promise for the safe and accessible therapy of both malignant and non-malignant blood disorders. Here we employed molecular barcoding normalized T-cell receptor (TCR) profiling to quantitatively track T-cell immune reconstitution after TCRαß-/CD19-depleted transplantation in children. We demonstrate that seemingly early reconstitution of αßT-cell counts 2 months after transplantation is based on only several hundred rapidly expanded clones originating from non-depleted graft cells. In further months, frequency of these hyperexpanded clones declines, and after 1 year the observed T-cell counts and TCRß diversity are mostly provided by the newly produced T cells. We also demonstrate that high TCRß diversity at day 60 observed for some of the patients is determined by recipient T cells and intrathymic progenitors that survived conditioning regimen. Our results indicate that further efforts on optimization of TCRαß-/CD19-depleted transplantation protocols should be directed toward providing more efficient T-cell defense in the first months after transplantation.

TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia.

We evaluated the depletion of TCR-alpha/beta cells from the graft of children with high-risk AML, who received transplantation from unrelated (n=20) and haploidentical donors (n=13). The preparative regimen included treosulfan, melphalan, fludarabine and anti-thymocyte globulin. Grafts were PBSC engineered by TCR-alpha/beta and CD19 depletion. The graft contained a median of 9 × 10(6)/kg of CD34+ and 20 × 10(3)/kg of αß-T cells. Post-transplant immune suppression included tacrolimus till day +30 and Mtx in 21 patients, tacrolimus in 5, Mtx in 2 and no prophylaxis in 5 patients. Sixteen patients received native or TCR-alpha/beta-depleted donor lymphocytes at a median of 47 (40-204) days. Median follow-up is 1.76 years. Primary engraftment was achieved in 33 patients (100%). Cumulative incidence of acute GvHD (aGvHD) grade 2-3 was 39 (26-60)%, half of them had skin-only aGvHD. Cumulative incidence of chronic GvHD was 30(18-50)%. Transplant-related mortality is 10(4-26)%. Event-free survival (EFS) is 60(43-76)% and overall survival (OS) is 67(50-84)% at 2 years. In a subgroup of patients, who received transplantation in CR, EFS is 66(48-84)% and OS-72(53-90)% at 2 years. Our data suggest that TCR-alpha/beta and CD19 depletion is a robust method of graft manipulation, which can be used to engineer grafts for children with AML.

Efficacy of plerixafor in children with malignant tumors failing to mobilize a sufficient number of hematopoietic progenitors with G-CSF.

Mobilization of suitable amounts of PBSCs with granulocyte-CSF (G-CSF) can be difficult in children. We report the results of using plerixafor in pediatric patients who failed to mobilize progenitors with G-CSF-based regimens. Thirty-three patients, median age 9 years (range 1-18 years) and median weight 29 kg (range 10-85 kg) were enrolled into the study. After 4 days of G-CSF stimulation, the median CD34+ cell count in peripheral blood was 10.4 per µL (range 0.27-23.0 per µL). Plerixafor was administered subcutaneously (0.24 µg/kg in 30 patients and 0.3 µg/kg in 3 patients) 11-12 h before apheresis. At the time of apheresis, CD34+ cell counts increased to a median of 44.1 per µL (range 8.4-357.0 per µL), a median 4.4-fold increase. Two patients (6%) failed to mobilize. Thirty-one patients underwent apheresis and in 27 >2 × 10(6) CD34+ cells per kg of body weight were collected after one procedure. In total, 31 of 33 patients mobilized successfully and the median number of cryopreserved CD34+ cells was 5.6 × 10(6) /kg body weight (2.7 × 10(6)-27.4 × 10(6)). Twenty-four patients underwent transplantation. Engraftment was achieved in all but one patient, who died on day +9 after hematopoietic stem cell transplantation. The median time of neutrophil and platelet recovery was day +12 and +16, respectively. Our study confirms that plerixafor has impressive efficacy and very modest toxicity in children.

BK virus nephropathy in a pediatric patient after hematopoietic stem cell transplantation.

We report the case of a seven-yr-old Caucasian girl who presented with progressive deterioration of renal function 13 months after HSCT for myelodysplastic syndrome. BK virus nephropathy was suspected and confirmed. After reduction of immunosuppression and treatment with IVIG, leflunomide, ciprofloxacin, and cidofovir, clearance of BK virus from blood was achieved, and further progression or renal failure was prevented. We believe that BK virus nephropathy should be considered in cases of renal function deterioration in all immunocompromised patients.

[The role of epitheliocytes secreting vascular endothelial growth factor, pancreatic polypeptide and glucagon in the development of oncological diseases of the stomach].

The present study included 104 patients with gastric disorders associated with Helicobacter pylori infection. Thirty of them presented with chronic atrophic gastritis (CAG), 30 with gastric ulcer (GU), 20 with adenomatous gastric polyps (AGP), and 24 with gastric cancer (GC). The control group was comprised of 12 practically healthy subjects. We elucidated the role of vascular endothelial growth factor (VEGF) and endocrine cells of gastric mucosa producing glucagon (GC) and pancreatic polypeptide (PPP) in the patients with GAG, GU, AGP and GC prior to and after the surgical intervention and following eradication therapy. It was shown that GAG, AGP, and GC were associated with the persistence of Helicobacter pylori infection and accompanied by hyperplasia of GC and PPP-secreting endocrine cells of gastric mucosa. GU was characterized by hypolasia of VEGF-secreting epithelial cells of the stomach and GC and PPP-secreting endocrine cells of gastric mucosa. The levels of VEGF, GC and PPP that directly or indirectly realize their pathological properties through H. pylori, Bcl-2, and proapoptotic protein BAX proved to be of high prognostic value as regards the evolvement and clinical course of gastric disorders associated with Helicobacter pylori infection. The study demonstrated that adequate eradication therapy in patients with H. pylori-associated diseases of the stomach significantly reduces the number of gastric cells secreting VEGF and has practically no effect on the amount of GC and PPP-producing endocrine cells of gastric mucosa.

[Results of hematopoietic cell transplantation in the first complete remission in children with acute myeloid leukemia from an intermediate risk group].

AIM: To analyze the results of allogeneic and autologous hemopoietic cell transplantations (allo- and auto-HCT) in children with acute myeloid leukemia (AML) from an intermediate risk group, most of which were performed using lower-intensity conditioning modes. SUBJECTS AND METHODS. The study enrolled 36 children from an intermediate risk group, who had undergone auto-HCT (n = 22) or allo-HCT (n = 14) in December 1994 to December 2008. The patients' age was 0.7 to 16.6 years (median 12.8 years). Chemotherapeutic conditioning regimens were applied to all the patients. Melphalan was a basic myeloablative agent in 83.3% of cases. RESULTS: With a median follow-up of 4.6 years (1.1-13.8 years), three-year relapse-free survival (RFS) was 80.4%; overall survival (OS) was 65.6%. Recurrences were documented only in 6 (16.6%) patients from the auto-HCT. Transplantation-associated mortality (TAM) was 13.8% (five patients died). After allo-HCT versus auto-HCT, RFS, OS, and TAM were 100 and 68.7% (p = 0.03), 93.2 and 55.5% (p = 0.02), and 7.1 and 18.2%, respectively. Acute and chronic graft-versus-host reactions developed in 57.1 and 23.1%, respectively. CONCLUSION: Transplantation of allogeneic hemopoietic cells from a compatible related donor in the intermediate risk group children with AML, by using melphalan-based conditioning regimen, demonstrates a high survival rate with the minimum toxicity.

[Transplantation of the bone marrow from a HLA-compatible unrelated donor after immunoablative conditioning in children with acquired aplastic anemia unresponsive to combined immunosuppressive therapy: preliminary results].

AIM: To analyze the efficiency of transplantation of the bone marrow from a HLA-compatible unrelated donor and continued immunosuppressive therapy (IST) in children with aplastic anemia (AA) unresponsive to 2 courses of IST. SUBJECTS AND METHODS: The study enrolled 14 children aged 2-16 years (median 9 years). A control group comprised 26 patients in whom IST was continued. The median interval between the diagnosis of AA and transplantation was 26 months (9-156 months). The conditioning regimen consisted of thoracoabdominal irradiation in a dose of 2 Gy, fludarabin (Flu) 100-150 mg/m2, cyclophosphamide (Cy) 100-200 mg/kg, antithymocyte globulin (ATG) in 11 patients and Flu, Cy, and ATG in 3. A graft-versus-host reaction was prevented with mycophenolate mefetil in all the patients, tacrolimus in 11, and cyclosporin A in 3. Donors were compatible for high-resolution typing of 10/10 and 9/10 alleles in 8 and 6 patients, respectively; the source of a transplant was bone marrow in 13 patients and granulocyte colony-stimulating factor-mobilized peripheral blood precursors in one case. RESULTS: Thirteen patients achieved primary engraftment after single transplantation; one patient did after repeat transplantation. Grades I to II graft-versus-host reaction (GVHR) developed in 9 patients; postengraftment life-threatening infections in 3, extensive chronic GVHR in 2, circumscribed GVHR in 7. All fourteen hemopoietic cell transplant recipients followed for a median 17.5 months (range 1-71 months) were survivors. CONCLUSION: The likelihood of good survival after unrelated transplantations in AA is much higher than that after continued IST: 100% versus 15 +/- 11%.

[Clinico-laboratory variants of the course and results of therapy of hepatitis-associated aplastic anemias in children].

AIM: To study clinical and laboratory characteristics of hepatitides and evaluate efficacy of immunosuppressive therapy and transplantation of the bone marrow in hepatitis-associated aplastic anemia (HAAA). MATERIAL AND METHODS: A retrospective analysis of case histories of children with HAAA was made. For all the patients standard tests for detection of aquired aplastic anemia and hepatitis were conducted. Transplantation of hemopoietic stem cells (THSC) from HLA-identical donors was made in 4 patients, 25 patients were treated with combined immunosuppressive therapy (antithymocytic globulin--ATG plus cyclosporin A -CsA), one patients received monotherapy with CsA, two--prednisolone and a short course of CsA, one child was untreated. RESULTS: Of 260 children admitted to hospital from April 1989 to July 2005 for aquired aplastic anemia, 33 (12.7%) met diagnostic criteria of HAAA. Boys to girls ratio was 267. Hepatitides were severe: median of alaninaminotransferase concentration was 1215 IU/l, aspartataminotransferase--789 IU/l, bilirubin--152.5 mcmol/l. Median of the interval from hepatitis symptoms to documentation of pancytopenia was 66 days (0-204 days). All four patients after THSC are alive for 30-72 months. Probability of complete remission after the first course of ATG+CsA is 0.72 +/- 0.09, probability of survival 0.81 +/- 0.07, median of the interval to transfusion independence--50 days. CONCLUSION: HAAA prognosis is good only in administration of up-to-date therapy. After seronegative hepatitis it is necessary to control hemogram parameters and in the presence of minimal cytopenia patients should be directed to hematological hospital.

Alkylator-free conditioning regimen for patients with acquired aplastic anemia, transplanted from genetically identical twins.

Allogeneic stem cell transplantation remains the best option for young patients with SAA. With genetically identical twin as an ideal donor, the majority of SAA patients require appropriate immunosuppression before and after stem cell transplantation to obtain long-term hematopoietic reconstitution. Alkylating agents, used during conditioning, are associated with short- and long-term toxic effects that lead to poor compliance of treatment and could compromise the quality of future life. Three SAA patients, transplanted from genetically identical twins without using alkylating agents during conditioning, showed rapid and sustained hematological reconstitution without any evidence of conditioning-related toxicity.

Fludarabine, low-dose busulfan and antithymocyte globulin as conditioning for Fanconi anemia patients receiving bone marrow transplantation from HLA-compatible related donors.

Allogeneic hematopoietic stem cell transplantation (SCT) from unaffected donors remains the only modality for the correction of hematological abnormalities in Fanconi anemia (FA) patients. We performed four HLA-matched related donor SCT using a novel irradiation and cyclophosphamide-free conditioning regimen. The protocol included fludarabine 150 mg/m(2), busulfan 4 mg/kg, and antithymocyte globulin 90 mg/kg. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A, MTX, and daclizumab. The engraftment and occurrence of full stable donor hemopoiesis was rapid in all cases with minimal short-term toxic complications. There were no infections or febrile episodes during the inpatient phase. Three patients developed acute GVHD grade I-II involving gut and skin and one patient progressed to extensive chronic GVHD. The preparative conditioning regimen is safe and associated with low organ toxicity and effective immunosupression for the stable engraftment in FA patients undergoing SCT with matched related donors.

Successful treatment of pure red cell aplasia with a single dose of rituximab in a child after major ABO incompatible peripheral blood allogeneic stem cell transplantation for acquired aplastic anemia.

Pure red cell aplasia (PRCA) is a well-known although infrequent hematologic complication after allogeneic bone marrow transplantation. PRCA occurs in cases of major ABO-mismatch between donor and recipient and is believed to be due to inhibition of donor erythroid progenitors by residual host isohemagglutinins. We report a 10-year-old boy with post-hepatitis aplastic anemia (AA) who developed PRCA after HLA-matched familial peripheral blood stem cell transplantation (SCT) following conditioning with Cph 200 mg/kg + ATG 90 mg/kg. Granulocyte engraftment occurred on day +18, platelet engrafted on day +40, while reticulocytopenia at 0% persisted until day +118, and erythroid precursors were totally absent from bone marrow. After a single dose of rituximab 200 mg/m(2)administered on day +118 PRCA resolved and on day +132 the reticulocytes rose to 5.7%. On day +139 the Hb reached 137 g/l and the erythroid lineage in BM increased to 21%. We conclude that due to the rapid recovery from PRCA and lack of side effects, rituximab should be tried as first-line treatment of PRCA after allo-SCT.

A successful cord blood transplant in a child with second accelerated phase chronic myeloid leukemia following lymphoid blast crisis.

We describe a 5-year-old girl with Ph(+) CML who received a cord blood transplant in a second accelerated phase after a very early lymphoid blast crisis. She was induced into CR by ALL-directed chemotherapy and then maintained with IFN-alpha2b together with weekly rotational chemotherapy. Nineteen months after diagnosis, her mother gave birth to an HLA-compatible sibling, whose cord blood was cryopreserved. The patient's second acceleration occurred 22 months after the CML diagnosis. The subsequent conditioning regimen included busulfan 16 mg/kg, Ara-C 12 g/m2 and melphalan 140 mg/m2. In order to prevent GVHD, CsA alone was administered, 3 mg/kg i.v. per day for a total of 40 days. The total number of nucleated cells infused was 0.8 x 108/kg, with CD34+ cells 1.8 x 106/kg and CFU-GM 1 x 104/kg. Engraftment occurred on day +35. Respiratory distress, severe VOD and grade II acute gastrointestinal GVHD complicated the post-transplant period. No chronic GVHD occurred. The girl is alive 23 months after transplantation with complete donor chimerism; both Ph chromosome and bcr/abl RNA are negative. Bone Marrow Transplantation (2000) 25, 213-215.