Impact of FLT-3 mutations on clinical features and response to the therapy in acute promyelocytic leukemia patients

FLT3 mutations are associated with poor outcome in acute myeloblastic leukemia [AML] patients. Only limited information is available about effects of FLT3 mutation on Acute Promyelocytic Leukemia [APL]. We investigated the prevalence and impact of FLT3 mutations on the clinical characteristics and the response to treatment in APL patients treated with arsenic trioxide [As[2]O[3]]. Blood samples were collected from 115 untreated APL patients and genomic DNA was extracted by the salting-out method. FLT3-ITD and FLT3-D835 mutations were investigated by PCR-RFLP. Mann-Whitney U test and Chi-square were used for data analysis. FLT3-ITD and FLT3-D835 mutations were detected in 16 [14%] and 13 [11%] of the patients, respectively. Both mutations were identified in two patients, so overall frequency of FLT3 mutations was estimated to be 23.5%. Patients positive for FLT3-ITD mutation had a higher rate of white cell counts [p= 0.005] and more frequent bcr3 type of PML/RARA fusion [p=0.04]. We have not found any significant association between FLT3-D835 mutation and the clinical characteristics of patients. Between the group with FLT3 Mutations and the group without, there was no significant difference in response to therapy. Complete remission induction with As[2]O[3] may be independent of FLT3 mutation status, so As[2]O[3] may be the first choice of APL especially in patients with FLT3 mutations. However, further studies on a large group of patients are necessary to confirm our findings

Population pharmacokinetics of oral high-dose busulfan in adult patients undergoing hematopoietic stem cell transplantation

Many factors have been reported that contribute to the wide intra- and inter-patient variability of Busulfan [Bu] disposition. The purpose of this study was to develop a population pharmacokinetic model and to determine the covariates affecting the pharmacokinetics [PK] of Bu in Iranian adult patients who received oral high-dose as a conditioning regimen before Hematopoietic Stem Cell Transplantation [HSCT]. A population PK analysis was performed in 30 patients who received an oral Bu and cyclophosphamide regimen before HSCT. Bu was given orally according to the protocol of the institution. In order to prevent seizures caused by Bu, phenytoin was administered orally one hour before each dose of Bu. A total of 180 blood samples were analyzed by HPLC and PK parameters were estimated by the non-linear mixed effect model by MONOLIX 3.1 program. A one-compartment model with an additive error model was used to describe the concentration-time profile of Bu. CL=13.4[1+ [0.141xDisease]], Vd=42.6[1+0.010x [Weight - 63.9]] Patients' disease and weight was found to be the determinant factors for clearance [CL] and the volume of distribution [Vd] according to Monolix analysis. The covariate entered in final model followed by these equations: In this limited study, the age [15-43 years] had no significant effect. For a patient weighting 60 kg, the typical CL and Vd were estimated to be 13.4 l/hr and 42.6 L, respectively. The interindividual variability of CL and Vd were 13.6 and 6.3%, respectively. There was no significant metabolic induction in these four days as is evident by comparing the trough levels of Bu. However it should be mentioned that, one tailed t-test p-values of the days of two and three, two and four and three and four were 0.083, 0.069 and 0.388, respectively. Results of this study showed that the type of disease was a determinant of CL and the weight of patient was a determinant of Vd for Bu population PK parameters. A reliable PK parameters and Css, estimated from only one plasma concentrations [5 hrs after the first dose], were validated. Since these methods require few sampling and are easy to be used, the limited sampling methods might be advantageous in the routine clinical practice

[Evaluation of the association of NOD2 gene polymorphisms with the occurrence of GVHD in acute myelogenous leukemia patients]

Graft-versus-host disease [GVHD] is one of life-threatening post-transplantation complications. Several recent studies have described a significant correlation between transplantation outcome and three single nucleotide polymorphisms [SNPs] in the NOD2 gene. This study was conducted to evaluate the association of NOD2 gene polymorphisms with the occurrence of GVHD in acute myelogenous leukemia patients who underwent HSCT from their HLA-matched sibling donors. We examined retrospectively NOD2 genotypes by PCR-SSP both in 124 patients who underwent HSCT and in their donors; then, the association of the genetic polymorphisms on acute and chronic GVHD was evaluated. Median follow up of patients was 40 months [range of 28-77 months]. Statistical analyses were performed using Chi-square test and SPSS software. Mutation incidence were the same between donors and recipients as 12.1%. In three of the patient-donor pairs [2.4%] SNPs occurred in both resulting in an overall frequency of 21.8% in patient-donor pairs. There weren't any significant differences between aGVHD and cGVHD incidence rates when donor/recipient pairs with SNPs were compared with the pairs without SNPs. aGVHD and cGVHD incidence rates in the former pairs were 52% and 56% and in the latter pairs 50.5% and 55%, respectively. No impact of NOD2 SNPs on incidence of acute and chronic GVHD was observed. Further studies are required to ascertain whether the findings of this study can be extended to other disease groups. In addition, further studies are required to identify the relevance of other SNPs

[ effect of arsenic trioxide treatment on mitochondrial apoptotic gene expression in acute promyelocytic leukemia cell line]

Acute promyelocytic leukemia [APL] is one of the most malignant forms of acute leukemia with a fatal course of only weeks which represents 10-15% of AML in adults. Arsenic trioxide as a single agent factor [without chemotherapy] is the treatment of choice for APL patients; it induces cell death through apoptosis but the mechanism by which arsenic targets apoptosis and dramatically affects gene expression remains poorly understood. Since arsenic is used as first line treatment in Iran, it is worth investigating its effect on expression of genes involved in APL. In this descriptive study, to understand the underlying mechanisms of cell death induction by arsenic, we treated NB4 cell line in a dose and time dependent manner. Extracting RNA and synthesis of cDNA, gene expression of apoptotic genes in mitochondrial pathway including caspase3, Mcl-1 and Bcl-2 was analyzed through Real-Time PCR. Our findings showed that As[2]O[3]-induced cell death was paralleled by reduced expression of the antiapoptotic protein Bcl-2 but the expression of Caspase3 and Mcl-1 did not change after arsenic treatment. These results suggest that changes in Bcl-2 gene expression may be one of the mechanisms of action of arsenic in induction of apoptosis, while Caspase3 and Mcl-1 gene expression are not affected by arsenic at the transcriptional level

Cell-based regenerative therapy as an alternative to liver transplantation for end-stage liver disease: experience from Iran

Several types of cells including mature hepatocytes, adult liver progenitor cells and human embryonic stem cells, fetal liver progenitor cells, bone marrow derived hematopoietic or mesenchymal stem cells, and um- bilical cord blood cells both in rodents and humans have been reported to be capable of self-replication, giving rise to daughter hepatocytes, both in vivo and in vitro. They have been shown to be able to repopulate liver in both animal models of liver injury and in patients with liver disease and to improve liver function. Human embryonic stem cell therapy seems to be a great promise for the treatment of liver cirrhosis, but there is no human clinical application due to ethical concerns or difficulties in harvesting or safely and efficiently expanding sufficient quantities. In contrast, adult bone marrow-derived hematopoietic or mesen- chymal stem cells, which can be easily and safely harvested, have been used in clinical trials to treat several chronic diseases including chronic liver disease. Cell therapy offers exciting promise for future treatment of cirrhosis and metabolic liver diseases, but significant technical hurdles remain that will only be overcome through years of intensive research. There is also serious concern about the long-term safety of stem cell therapy and the possibility of tumor development. Herein, we present our experience with cell therapy in treatment of chronic liver disease in Iran

[ effectiveness of non-myeloablative stem cell transplantation and DLI as a selective treatment in class III beta-thalassemic patients]

At present, the only curative treatment for beta-thalassemia major is allogenic bone marrow transplantation accompanied with considerable mortality and morbidity in class III beta-thalassemia. Regarding few case reports on successful non-myeloablative stem cell transplantation in class III beta-thalassemic cases, we evaluated the effectiveness of this type of allogenic stem cell transplantation, considering less toxic non-myeloablative conditioning regimen. In this prospective study in Shariati Hospital bone marrow transplantation center during 2001-3, 13 class III beta-thalassemia patients [on the basis of history and physical examination and liver biopsy] were transplanted with peripheral blood and bone marrow stem cells from their HLA-identical siblings. Non-myeloablative conditioning regimen included fludarabine; busulan; antithymocyte globulin. Graft versus host disease [GVHD] prophylactic regimen was cyclosporin and metothrexate. In the case of the declining chimerism, the patients were treated with donor lymphocyte infusions [DLI]. The conditioning regimen was tolerated well without any considerable toxicity in hematologic, gastrointestinal and pulmonary systems. Five [38.5%] patients had acute and 2[15.4%] had chronic GVHD. Two patients died after transplantation. While two cases had a thalassemia-free survival. Although associated with high graft failure and the recurrence of disease, nonmyeloablative stem cell transplantation may be used as a curative, less toxic posttransplantation treatment for class III beta-thalassemia

Results of hematopoietic cell transplantation in pediatric leukemia

Hematopoietic cell transplantation [HCT] is an accepted treatment for acute myeloid leukemia [AML] in first remission, the treatment of choice for chronic myeloid leukemia [CML] and high risk groups of ALL who relapse with conventional chemotherapy. We assessed results of HCT for pediatric leukemia in our center. A total of 92 children, 63 with diagnose of AML, 23 with ALL and 6 with CML received allogeneic transplantation from HLA full matched siblings [57.6%] and autologous transplantation [42.4%]. Source of hematopoietic cells were peripheral blood 83.7%, bone marrow 15.2% and cord blood 1.6%. The median transplanted nucleated cells were 6.4 +/- 4.7 X 10[8] /Kg [body weight of patients] and mononuclear cells were 5.5 +/- 2.9 X 10[8]/Kg. The most common conditioning regimens were cyclophosphamide + busulfan. Prophylaxis regimen for GVHD was cyclosporin +/- methotrexate. GVHD occurred in 50 [54.3%] patients. Eighty five of children had engraftment, 26 [28.6%] relapsed and 57 [62%] are alive. The most common cause of death was relapse [68.6%]. Five years overall survival of patients with AML and ALL were 49% and 44% respectively and disease free survival of them were 52% and 49%. One year overall survival and disease free survival of CML was 57%. Overall survival increased with increasing age of patients at transplantation time [P = 0.06]. Longer survival significantly related to earlier WBC and platelet recovery [P < 0.0001 and P = 0.006 respectively]. Considering acceptable overall and disease free survival of patients after HCT, we concluded that is a good modality in treatment of leukemia of children

CMV detection and monitoring in bone marrow transplant [BMT] recipients by Real-Time PCR [RQ-PCR]

Cytomegalovirus [CMV] is an important pathogen in patients undergoing bone marrow transplantation. The prevalence of CMV varies from 30-100% in different countries as shown by seroepidemiological studies. Only 20-25% of patients develop CMV disease. Because of the similarity between CMV and GVHD and the different therapies required, detection of viral load will be effective in patients' survival. 51 recipients of BMT were monitored for 100 days post-BMT during which the samples were collected weekly. The Real-Time PCR was developed for quantitation of CMV viral DNA, using TaqMan tecnnology. For generation of standard curve, UL83 gene from CMV was cloned into a plasmid using a T/A cloning procedure. RQ-PCR assay was preformed in parallel with pp65 antigenemia assay on 415 samples. The results obtained by both techniques were significantly correlated [p < 0.01]. We could detect 13x10[1] -15x10[7] [CMV DNA copies/2x10[5] cells] by RQ-PCR method. About 76% of patients developed at least one episode of CMV reactivation. First positive result of RQ-PCR appeared 13 days earlier than of pp65 antigenemia. After preemptive therapy, 16 days were required to achieve negative result by RQ-PCR. Both assays were highly correlated; however, RQ-PCR was more sensitive than the antigenemia assay. After preemptive therapy, negative results of RQ-PCR were the best indicator to determine the endpoint of treatment and its success

Evaluation of the best condition for ex vivo expansion of hematopoietic stem cells for the propose of cord blood transplantation

Umbilical cord blood [CB] has been identified as a rich source for hematopoietic stem cells [HSCs], and has provided an alternative to bone marrow transplantation. The use of ex vivo expanded cells has been suggested as a possible means to accelerate the speed of engraftment in cord blood [CB] transplantation. The main aim of our study is to find the best culture media and condition to increase number of CD34+/CD38- hematopoietic stem cells in cord blood for transplantation. Mononuclear cells [MNCs] were seperated from cord blood and cultured in RPMI1640 with 10% fetal calf serum [FCS] or 10% cord blood plasma [CBP] or serum free media [SF]. Culture media contained 50ng/ml of Interlukin 6 [IL6], IL3, Thrombopoietin [TPO] Stem cell factor [SCF] and flt3-ligand. Cells were cultured for two weeks and number of CD34+/CD38- cells and total MNCs measured at days 0, 7 and 14. At 14 days culture mean fold of expansion of CD34+ and CD34+/CD38- cells was 20.4 and 57.4 for FCS, 5.6 and 10.3 for SF and 10.8 and 4.7 for CBP culture media. Due to efficacy and predictability of SF media for cell expansion and because of its better safety for allergic reactions and microbial contamination [in comparison to animal products containing media] and enough expansion for clinical applications, we suggest that SF media is better than CBP or SF from clinical points of view

Evalution of the relationship between vitamin d receptor gene polymorphism [FOK I] and thyroid cancer

Background and purpose: Vitamin D is an antiproliferative agent against cancer cells and regulates cell differentiation. It acts via Vitamin D Receptor [VDR]. The VDR gene contains a Start Colon Polymorphism [SCP] that can be detected with the restriction enzyme Fok I. Previous studies report an association of SCP and some diseases and some suggest that this polymorphism alters VDR function. As no studies so far have reported the association between Fok I genotype in Thyroid cancer, this study is intended to determine the association of Fok I polymorphism of VDR with thyroid cancer risks in Iranian population

Methods and Materials: 58 patients with papillary carcinoma, 13 patients with follicular carcinoma and 82 controls participated in a case-control study. A PCR-RFLP method used to determine VDR gene polymorphism in start codon characterized by the restriction enzyme Fok I. 95% confidence intervals and odds ratio were calculated for testing the relationship between Fok I polymorphism and thyroid cancer

Results: The odds ratio for the Fok I polymorphism on thyroid cancer was 0.39 [95% CI, 0.12-1.27] witch signifies no relationship between this polymorphism and the ris of thyroid cancer

Conclusion: As no relationship was found between this polymorphism and thyroid cancer, other genetic or environmental factors may be considered in thyroid cancer

[Cross-resistance to anticancer drugs in acute myeloblastic leukemia Pgp expressing K562 cell line]

Drug resistance remains one of the most important clinical obstacles in the treatment of some cancers. This drug resistance referred to as Multidrug Resistance [MDR] induces cross-resistance to many chemotherapy agents such as anthracyclines, vinca alkaloides, epipodophyllotoxins and Taxol. MDR is most likely due to the reduction of drug accumulation with an energy-dependent drug efflux pump. This drug pump is a 170 kDa transmembrane glycoprotein [Pgp]. We developed a resistance subline of K562 by stepwise increase in concentration of Doxorubicin, and Pgp expression was verified by flowcytometry and RT-PCR methods. Cross resistance of the resistant cell line to Etoposide, Vincristine and Taxol was analyzed by MTT assay. IC[50] [the level of drug concentration inhibiting 50% of cell growth] of Doxorubicin, Etoposide and Taxol of parental K562 came out to be 100ng/ml and it was 50 ng/ml for vincristine. IC[50] levels of these drugs on resistant K562 were 500, 500, 450 and 450ng/ml. These drugs also displayed 5-, 5-, 4.5-, and 9- fold resistance respectively. According to the results, expression of Pgp confers MDR phenotype to the K562 cell line and makes it resistant to most of anticancer drugs including anthracyclines, vinca alkaloides, epipodophyllotoxins and taxans. This MDR phenotype is a major obstacle of cancer treatment and in recent years investigators are trying to reverse it by gene therapy

Arsenic trioxide compound modulates multiple myeloma phenotypes: Assessment on cell line models

Recent evidences suggest that multiple myeloma phenotypes [MMPs] are involved in the infiltration of multiple myeloma-affected marrow foci. In this study, the effects of arsenic trioxide on the invasive and angiogenic phenotypes of multiple myeloma [MM] cell line were assessed on a dose-response and time-course basis. Multiple myeloma cell line, Karpas 707, was treated with step-wise elevated concentrations of arsenic trioxide compound at 24, 48, and 72 h intervals. Cytotoxicity was assessed with a colorimetric assay. Potential antiinvasive phenotype was analyzed with MMP-2 zymography. To verify directly the anti angiogenic effect, F1 endothelial cell line was also treated with arsenic and the dose-dependent cytotoxicity was assessed with a colorimetric assay. Apoptotic properties of arsenic trioxide compound were investigated using TUNEL assay. The significant dose-dependent inhibitory effects of arsenic trioxide on MMP-2 were seen at given concentrations. Cytotoxicity analysis revealed much higher cell death than untreated cells [P< 0.01], both in Karpas 707 and F1 endothelial cell lines. Colectively, this study showed that arsenic trioxide might potentially elicit anti-invasive anti-angiogenesis properties in the treatment of myeloma dissemination process. In addition, the concurrent inhibition of MMPs activity and endothelial cell proliferation could compose the scenario of neoangiogenesis inhibition in the marrow-infiltrated foci

[Early hepatic complication in frst year after bone marrow transplantation in major beta thalassemic patients]

Bone marrow transplantation is a good therapeutic modality for beta thalassemia. Liver complications is one of the major causes of morbidity and mortality following BMT. Determination of the factors of liver injury leads to earlier diagnosis after BMT and improves prognosis. We studied 113 major Beta thalassemic patients who have been transplanted from 1990- 2000 in bone marrow transplantation center of Shariati Hospital. 62 were male and 51 were female. 27 patients were class one, 56 were class two and 30 were class three. The median age of each classes were 6.5, 6.3 and 8.7 year. Conditioning regime consisted of busulfan [3.5-4mg/Kg] and cyclophophamide [40-50 mg/kg]. For GVHD prophylaxis we gave cyclosporine +/- metothrexate. Grade of liver fibrosis defined by biopsy in all patients before BMT. All patients and their donors tested for HBsAg, HBsAb, HCVAb, CMVAb with RIA method. We assessed causes of liver dysfunction before and after transplantation and effect of high ferritin level on liver function. Hepatic dysfunction in first year after transplantation were seen in 86 [76%] patients. Causes of liver dysfunction were consisted of 53.1% GVHD, 15.93% cyclosporine hepatotoxicity, 5.3% conditioning regime hepatotoxicity and 1.77% VOD. In all three classes hepatic GVHD, cyclosporine toxicity, death and normal liver function post BMT had significant relation with hepatic dysfunction before BMT [p=0.001]. In patients with ferritin level more than 1000, there were significant hepatotoxicity with conditioning regime [p=0.001]. 17 [15.04%] of patients have been died. In this study we determined incidence and causes of hepatic dysfunction before and after BMT in major beta thalassemic patients. According to our study the incidence of hepatic dysfunction was 76.1% and hepatic GVHD and drug hepotoxicity were the most common causes of hepatic dysfunction in all three classes. Serum ferritin level had not significant relation to GVHD, cyclosporine hepatotoxicity and VOD

Frequency of BCR-ABL fusion transcript in Iranian patients with chronic myeloid leukemia

Reverse transcriptase-polymerase chain reaction [RT-PCR] assay is a useful tool for the detection of fusion transcript resulting from specific chromosomal translocation of the leukemia cells. A specific chromosomal abnormality, the Philadelphia chromosome [Ph], is present in 90% to 95% of CML patients. The aberration results from a reciprocal translocation between chromosome 9 and 22, creating a BCR-ABL fusion gene. There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a p210 protein. Another fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 pro-tein. Another, less common fusion genes are b3a3 or b2a3 [p203] and e19a2 [p230]. The incidence of one or other rearrangement in chronic myeloid leukemia [CML] patients varies in different reported series. In general, fusion transcripts are determined individually, a process which is labor intensive in or-der to detect all major fusion transcripts. This study was designed to determine the frequency of different fusion genes in 75 iranian patients with CML. peripheral blood samples were analyzed by multiplex reverse transcriptase poly-merase chain reaction [RT-PCR] from adult patients to detect all types of BCR-ABL transcripts of the t [9:22] and found that all cases were positive for some type of BCR/ABL rearrangement. Most of our patients showed b3a2 fusion gene [62%], while the remaining showed one of the transcripts of b2a2, b3a3, b2a3, e1a2 or coexpression of b3a2 and b2a2. The rate of coexpression of the b3a2 and b2a2 was 5%. In contrast to the other reports, we did not see any coexpression of p210/p190. This may reflect either the sensitivity of the detection techniques used or the possibility of genetic differences be-tween the populations studied. Coexpression may be due to alternative splicing or to phenotypic varia-tion, with clinical course different from classical CML

Clinical, biological and pathological characteristics of breast cancer patients at the Taleghani University Hospital in Kermanshah, Iran

Breast cancer is the most common of all malignant neoplasms in women worldwide. This study aims to demonstrate certain biological, clinical and pathological characteristics of patients treated at the university hospital oncology unit. A descriptive study was conducted during a period of 2 years, from October 2003 through September of 2005 in Kermanshah, Iran. 555 patients were selected to participate, representing all the cases diagnosed and treated for breast cancer. Data was gathered according to questionnaires and pa-tients' records. The mean age at which breast cancer was first diagnosed was 46.5 +/- 11.6 year of age with 89% of tumors being infiltrating intraductal carcinoma. The majority of the patient population had tumors stage II and grade II. Mean tumor size was 2.14 +/- 0.57 centimeters. 58% of the tumors were localized to the upper outer quadrant of the affected breast and 89% of the patients received modified radical mastectomies with almost a 92% two year survival. Highest prevalence of breast cancer was recorded in the 40-49 [mean 46] years of age group which compares favorably with studies done under similar circumstances. Tumor size, grade, stage, tumor marker analysis, metastasis and other disease characteristics portray patient population tendencies for breast cancer patients in Kermanshah, Iran

Quantitative analysis of Epstein - Barr virus DNA load in bone marrow transplant recipients by using real-time PCR

Quantification of Epstein - Barr virus [EBV] in peripheral blood mononuclear cells [PBMNC] of allogenic bone marrow transplant [BMT] recipients is important because EBV-associated posttransplant Lymphoproliferative disease [PTLD] can occur after transplantation due to immunosup-pression therapy. To this end we chose Real-Time PCR using TaqMan probe. For the standard curve, we cloned BALF5 gene of EBV into a plasmid vector. After purification of the EBV-clone and calculation of plasmid copy number, the standard curve was constructed by using serial dilution of the plasmid clone. We were able to detect from 2 to 107 copies per 2x105 PBMNC with wide linear range. The mean EBV DNA copy number was 103.7 copies per 2x105 PBMNC. In this study, No patient of 35 BMT recipients [275 PBMNC samples] developed PTLD during five months follow up post transplant. EBV copy numbers in 22 samples [3 patients] out of 35 BMT recipients were higher than cut off value with symptoms like fever and pulomonary noddes [9%]. The virus load in one patient in the last sample obtained was 72400 copies. We detected low levels of EBV DNA in 20 BMT patients [57/1%]. Real-Time PCR is useful to measure virus load in PBMNC. Detection of EBV in PBMNC samples may be valuable predictive marker to prognosis PTLD. Further studies need to determine ac-curate viral cut off value for treatment patients at risk for PTLD

Effects of chimerism on graft versus host disease recurrence and survival after HLA identical marrow transplantation in Iran

The co-existence of recipient's hamatopoietic systems after allogeneic marrow transplantation is called mixed chimerism. Chimerism analysis provides a national method of different conditioning regimens, graft-versus-host disease [GVHD], prophylactic regimens, and cellular therapy to promote engraftment. The association of mixed chimerism with acute graft-versus-host disease [GVHD], disease recurrence, survival, and relapse free survival was investigated in 91 patients 12 and 79 of whom underwent either bone or peripheral blood HLA-identical marrow transplantation respectively. Chimerism was assessed using multiplex amplification of shorty tandem repeats [STR-PCR].cases included thalassemics [19 subjects], AML [29], ALL [20], CMT [18] and others [5].Median age was 21 [age range of 3-50]. There were 38 females [41.8%] and 53 males [58.2%]. Conditioning was busulfan plus cyclophosphamide in 34 patients, busulfan plus fludarabin in 51 patients and busulfan plus fludarabin plus anti-thymocyte globulin in 6 patients. Median of follow up was 13 months. Data was analyzed using SPSS statistical software. On day 30 after transplantation, mixed chimerism [MC] was observed in 15 patients [16.5%], complete donor chimerism [CC] in 72 patients [79%], and no chimerism in 4 patients. The incidence of acute GVHD was significantly lower in mixed chimeras that in complete chimeras [p=0.01] but there was no significant difference in acute GVHD grade [I, II vs. III, IV] between two groups. The incidence of relapse and overall survival were 17.6% and 88.9% respectively showing no significant difference between MC and CC. Relapse free survival was 80.2% and significantly different between two groups. Despite some previous reports, we found no significant difference in survival and relapse rate between MC and CC. Relapse free survival was 80.2% and not significantly different between tw ogroup

[Evaluation of chimerism in interphase nuclei of peripheral blood of patients with sex-mismatch bone marrow transplantation]

Fully quantitative cytological techniques for the analysis of hematopoietic chimerism are very limited and are largely restricted to sex - chromosome detection after sex - mismatched bone marrow transplants [BMTs]. The aim of the present investigation was to evaluate the application of FISH technique in peripheral blood interphase nuclei of three patients who had received sex - mismatched bone marrow transplants. The FISH technique shows 40% to 85% [average 61%] chimerism in these patients. All the three studied patients having undergone bone marrow transplants have achieved complete remission now. Evaluation of mixed chimerism has potential applications in controlling self-reactions avoiding rejection of the transplant