| Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is an important method and the only way to radial cureβ-thalassemia.We have applied this method for more than 30 years. Hemorrhagic Cystitis(HC) is one of the common complications, which often extends the hospitalization days and increases the expenditure of the patients and it badly affects the life quality of the patients by damaging their kiney function as to threaten their life. As we have only applied HSCT in children for just a few years, there is rare study on HC after HSCT in our country. How to prevent and cure HC appropriately and efficiently is directly correlated with the patients' living quality in long term. In this study, we sort out and analyzed the clinical datas for patients who were undergone Allo-HSCT, aiming at exploring the risk factors for HC occurrence and HC clinical features, so as to provide a guidence for preventing HC in children.Method:We retrospectively analyzed 100 cases of HSCT, who were undergone the operation in our department from Apr.2000 to Dec.2009. All cases were homozygotic or double heterozygotic.33 cases were treated with Allo-PBSCT(3 were parent donors,29 were unrelated donors,1 was sibling donor; 30 cases were HLA full matched), with the average age 7.07±2.18years.54 cases were treated with Allo-BMT(29 were sibling donors,17 were unrelated donors), with the average age 6.08±2.66years.; while 13 cases were Allo-BMT+Allo-CBT (all were HLA full matched),with the average age 5.88±1.69years.1,Criteria for case choosing:(1) All the patients without HC occurrence and were hospitalized for more than two months; (2) All the patients with HC occrence were take into account for this study; (3) Those who were undergone a second or the third transplantaion is taken as a new individual in this study.2,Preconditioning RegimenAccording to types of transplantation, preconditioning regimen is mainly based on Bu+Cy, with the complement of Flud and TBI or TT or ATG, Furthermore, the second transplantation preconditioning regimen is TBI+Cy. The dosage of Bu is 8 mg/kg to 24 mg/kg:16 mg/kg for those who are younger than 5 years old and less than 16 mg/kg for those older than 5 years old.the dosage of IVBU is 2.8～4.4 mg/kg/d. The dosage of Cy is 120-200mg/kg, The total dosage for TBI is 6 to 8 Gy; the dosage rate is 6.5 to 7 cGy/min. Crystalline lens and lung shielding ensure a total amount of less than 6.5 Gy. The dosage of Flud is 30-40mg/m2. d×5d, used 17 to 15 days before transplantation. The dosage for the second transplantation is Cy (60mg/kg. d×2d) +TBI (3Gy).3,Classification and graduation of GVHD and its preventionClassification of aGVHD are based on acreag of skin that are involved and the injure of gastrointestinal tract and liver. ATG., CsA and MTX were used in transplantation patients before 2001; ATG, CsA and MMF were used after 2001. ATG, CsA or FK-506, MMF and MTX were used in unrelated donors for transplantation. Intravenous injection of CsA was conducted for 24 hours the day before transplantation. The concentration of Carbinoxamine Compound Drops will be controlled between 150 to 250ug/L. MTX will be used in the first, third, sixth and eleventh day in respective dosage of 15mg/m2,10 mg/m2,10 mg/m2,10 mg/m2 and ATG 10 to 40 mg/kg (rabbit),90mg/kg (horse).Carbinoxamine Compound Drops concentration of FK-506 is 10 to 25ug/L. CsA and FK-506 will be taken by mouth once the patients can eat normally. MMF will be taken by mouth following the instruction of 0.5g to 1.0g/d.4,The detection and treatment of CMV(1)Before regimen, Ganciclovir will be used in patients regardless of the existence of cytomegalovirus infection. (2)After transplantation, quantitative detection of HCMV-DNA should be used once the amount of medium-grain cells is over 0.5×109/L; Ganciclovir anti-virus treatment will be performed according to blood test and virus clones and severity of hematuria.5,The other preservation of complicationHVOD:Ursodeoxycholic acid(-8d), Heparin sodium(+1d～+20d); Mycetes: Itraconazole (+6d 10mg/kg/d,+7d 5mg/kg/d); Infection:health examination before hospitalization; asepsis food and drink after in transplantation cabin, antibiotic preservation for three days in the day of transplantation.6,Engraftment detectionBlood rountine test every day. When neutrophil cells in peripheral blood is more than 0.5×109/L, platelet is over 20×109/L, the blood type of peripheral blood, marrow and chromosome should be tested in the 28th to 60th day after implantation. The changes of chromosome will be checked by FISH if patients and donors are different genders. A quantitative detection of HLA will be conducted on DNA short-distance repeated serial polymorphism analysis. 7,Diagnosis and classification of HCHC can be diagnosed, if hematuria complicated with urinary passage stimulated symptoms(such as frequent micturition, urgent urination, udynuria etc, but excluding bacteria infection and pharmacologic hematuria or others such as blood vessel diffused cruor, poly-organ functional obstruction or septicemia) can be detected in children patients with microscope or by eyes.,. According to the severity of hematuria, HC should be classified in compliance with the classification standard from WTO.8,Prevention of HCPreconditioning medication contains cyclohosphamide. When Cyclohosphamide is adiministrated, drip liquid therapy, urine alkalization and diuretics should also be supplemented. From the day we used cyclohosphamide, we also prescribed Mesna to reduce the toxicity. Once a definite diagnosis is made, drip liquid therapy, urine alkalization should also be applied. Antivirus therapy should be guided when quantitive detection of HCMV shows postive. If no remarkable improvement is observed after these therapies but case of urethra obstruction is observed, we should catheterize the ureter or rinse bladder with nitrofural solution. When pains get fierce, we administrate rotundine, Tramadol Hydrochloride and 654-2 to release for them. For those whose platelets are below 10×109/L, we input platelets or red blood cells and so on.9,Statistics AnalysisWe use statistics analysis software-SPSS13.0 to analyse patients age, gender, transplantation type and HLA matching, donor resource, aGVHD severity, HCMV infection, occurrence of HVOD as well as comparation of HC occurence with and without TT, comparations of HC occurrence with Cy usage before Bu and after Bu, Bu using method and ferritin, donor resources with aGVHD, Bu using method with aGVHD, type of transplation with aGVHD, the age with aGVHD and the age with ferritin,χ2 test is used to compare, while t Test is use to compare between HC group and non HC group in databases of MNC, CD34+, NEU, HGB, PLT, Cy, ferritin, IVBU. Kaplan-Meier method is used to analyze Neu, PLT and Hb average time of Allo-PBSCT, Allo-BMT and Allo-BMT+Allo-CBT group. Non-conditional Logistic regression analysis is used to analyze HC risk factor.Result1,The occurrence of HCThe occurrence rate of these 100 cases is 19%(19/100), with the median day 20.63 (6-36)d, patients'mean age 7.38±2.683y and lasting median day 9.11(3-27)d.5 cases were early-onset and 14 were late-onset. All the patients had irritative symptoms of bladder, such as frequent urination, urgency and dysurea. The only case ofⅢ°showed azotemia and examination of kiney function (BUN=13.8mmol/l, CRE <100umol/L), the others show no other clinical symptom.2,Data comparation of HC group and non-HC groupPatients'age had significant difference between HC and without HC(P=0.031). Ages of HC group are older than that without HC. But no significant difference between CD34+ count, MNC count,CY dosage, Ferritin and hemogram recover interval.3,Influential factors for HC occurrenceWe compared HC occurecre of each group by analysing factor such as age, gender, aGVHD, type of transplantation, HLA matching, donor resources, CMV infection, post-transplantation from Dec.2008-Nov.2009, the occurrence of HVOD and use with and without TT, Cy using before Bu and after Bu, grade of Ferritin. The result indicates age and aGVHD affect the occurrence of HC(P=0.049,P<0.05); But no significant differecne is found among the other Influential factors.4,Donor resources and BU using method Different donor resource has a significant relation with aGVHD (P=0.012). aGVHD risk is higher in patients undergone unrelated donor than that in sibling and parents. But there was no significant difference between BU using method and aGVHD(P=0.969).5,Haematogenesis reconstitution33cases of Allo-PBSCT,55 cases of Allo-BMT and 13 of Allo-PBSCT+Allo-CBT, the median days of NEU>0.5×109/L are 16.0 (13.20～18.80) d,12.0(11.11～12.90)d,13.0(11.59～14.41)d. respectively, which shows significant meaning between Allo-PBSCT and Allo-PBSCT+Allo-CBT (P=0.024). and also between Allo-PBSCT and Allo-BMT (P=0.023); The median days of PLT>20×109/L are 21 (18.19～23.81) d,24(20.41～27.53)d,29 (24.30～33.70)d respectively, which shows significant difference between Allo-PBSCT and Allo-BMT (P=0.015). The median days of HGB>90g/l are 22 (19.77～24.237)d,23(18.50～27.50)d,35(29.13～40.87)d respectively, which shows no significant difference among the three groups. All the engraftment evdence are tested in +28d, of which 4 cases showed engraftment versus host symptom and excluded in two months,2 were in the condition of engraftment and host mixed, and the rest are all 100% engrafted. HC and non HC group shows no remarkable differnce in the timing of reconstructing stem cells.6,Analysis of independent risk factors for HCWe compared HC occurecre of each group by analysing factors such as age, aGVHD, type of transplantation, HLA matching, donor resource, CMV infection post-transplantation from Dec.2008-Nov.2009, the occurrence of HVOD, use with and without TT, use with and without TBI, Cy using before Bu and after Bu, Grade of ferritin and BU using method. The result indicates aGVHD is a risk factor of the occurrence of HC(P<0.05). Patients older than 6 years old have a higher risk than that younger than 6 years old. Cy befor Bu has a higher risk than that after. Orally in takes BU has a higher risk that intravenous. Patients with aGVHD has a higher risk than that without. Allo-PBSCT also has higher risk than Allo-BMT. Conclusion:As for Children withβ-thalassemia undergoing Allo-HSCT, age is the main influential factor. for children older than 6 years, we should be cautious to the occurrence of HC so as to prevent and treat early in clinic. Meanwhile, Polyoma BK virus and adenovirus type 11 should beunder surveillance in clinic. Donor resources, aGVHD and HC are the main risk factors. Therefore, HLA highly matches is required in clinic. Blood relative and young donors are preferred as to reduce HC occurrence. Using Cy before Bu has a higher risk than that after. Orally in takes BU has a higher risk than intravenous.we must add strength preservation about HC in Allo-PBSCT. |
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