Prevalence of abnormal in vitro closure time using the Platelet Function Analyzer-100 in chronic kidney disease patients and analysis of associated factors.

AIM: Platelet Function Analyzer- 100 evaluates platelet function by determining time to occlusion of an aperture in a membrane coated with collagen and epinephrine (CEPI) or collagen and ADP (CADP) during the flow of citrated whole blood. We sought to determine prevalence of abnormal in vitro closure time (CT) in chronic kidney disease (CKD) patients and to analyze associated factors. MATERIALS AND METHODS: CEPI-CT (normal, 82 - 182 sec in Korean), CADP-CT (normal, 62 - 109 sec), CBC, serum creatinine (Cr) and blood urea nitrogen (BUN) were measured in CKD patients, 30 with Stage I, 36 with Stage II, 30 with Stage III, 56 with Stage IV, 283 with Stage V (79 with pre-dialysis Stage V, 130 on chronic hemodialysis (CHD), and 74 on chronic peritoneal dialysis (CPD)). Estimated glomerular filtration rate (eGFR) was calculated with a MDRD equation. RESULTS: Abnormal CEPI-CT and CADP-CT occurred in < 15% of Stage I - III, 20% of Stage IV, and 41% and 54%, respectively, of Stage V patients. There were no differences in prevalence of abnormal CEPI-CT and CADP-CT among predialysis Stage V, CHD and CPD patients. CEPI-CT and CADP-CT were correlated with BUN, Cr and platelet counts in predialysis patients, and with platelet counts in dialysis patients, and CEPI-CT was correlated with BUN, Cr in CPD patients. Neither, however, was correlated with age, gender, hemoglobin or hematocrit. CONCLUSION: Prevalence of abnormal in vitro CT increases as stage worsens in CKD patients. In vitro CT is correlated with BUN, Cr and platelet counts in predialysis and total CKD patients.

Robotic tumor-specific mesorectal excision of rectal cancer: short-term outcome of a pilot randomized trial.

BACKGROUND: Laparoscopic colorectal resection has become popular. The recently developed da Vinci Surgical System promises to facilitate endoscopic surgery and overcome its disadvantages. This study therefore aimed to compare the short-term results between robotic tumor-specific mesorectal excision (R-TSME) using the da Vinci Surgical System and conventional laparoscopic tumor-specific mesorectal excision (L-TSME) in rectal cancer patients. METHODS: Between April 2006 and February 2007, 36 patients were randomly assigned to receive R-TSME or L-TSME. During the study, 18 patients underwent robotic low anterior resection using the da Vinci Surgical System, and 18 patients had conventional laparoscopic low anterior resection. Patient characteristics, perioperative clinical results, complications, and pathologic details were compared between the two groups. RESULTS: The patient characteristics were not significantly different between the two groups. The mean operating time, hemoglobin change, and conversion rate were not significantly different between the groups. Complications were treated conservatively and did not require surgical intervention in the R-TSME group. The average length of stay was 6.9 +/- 1.3 days in the R-TSME group and 8.7 +/- 1.3 days in the L-TSME group (p < 0.001). The specimen quality of the R-TSME group was acceptable. CONCLUSION: Tumor-specific mesorectal excision was performed safely and effectively using the da Vinci Surgical System and the perioperative outcomes were acceptable.

Quantitative Epstein-Barr virus viral load monitoring in pediatric liver transplantation.

The aim of this study was to determine whether the implementation of the quantitative Epstein-Barr virus polymerase chain reaction (qEBV-PCR) test in 2003 decreased the incidence of posttransplant lymphoproliferative disease (PTLD) and PTLD-related mortality. Of the 128 children who underwent liver transplantation between January 1994 and May 2007, 110 (85.9%) survived. Patients were divided into pre (1994 to 2002; n = 86) and post (2003 to 2007; n = 42) EBV-PCR groups. There were no between-group differences in mean age, percentage of patients < 12 months old, or seronegative for EBV. The incidence rates of primary EBV infection in the pre- and post-EBV-PCR groups were 14.0% and 33.3%, respectively (P < .05). In contrast, the pre- and post-EBV-PCR groups showed similar incidences of symptomatic EBV infection (31.3% vs 35.7%; P = .625) and PTLD (10.5% vs 9.5%; P = .869), but different survival rates (80.2% vs 97.6%; P < .001). Five of nine PTLD patients in the pre-EBV-PCR group died of PTLD, but there was no PTLD-related mortality in the post-EBV-PCR group, indicating that PTLD-related mortality decreased after qEBV-PCR monitoring. These findings suggested that frequent EBV viral load monitoring and subsequent modulation of immunosuppression can reduce PTLD and PTLD-related mortality among pediatric liver transplant patients.

Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.

Clinical impact of imatinib was evaluated in 20 patients (median age, 37 years; range, 15-67 years) with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), who were administered with induction chemotherapy of daunorubicin, vincristine, prednisolone, and L-asparaginase, along with imatinib 600 mg/day during remission induction and 400 mg/day during consolidation courses. One patient died on day 14 from septic shock, while the remaining 19 achieved complete remission (CR). In total, 15 patients underwent allogeneic hematopoietic cell transplantation (HCT) during first CR. After median follow-up period of 799 days, six patients experienced recurrence; two with early recurrence within 100 days, one with leptomeningeal recurrence at 11 month, and three with post-HCT recurrence. Eight patients died. Median CR duration (821 days) and median patient survival (894 days) in the study were significantly longer by 2.9- and 2.3-fold, respectively, when compared to those of 18 historical patients treated with same regimen of combination chemotherapy without imatinib. Toxicities of the combined treatment were manageable and included grade 4 myelosuppression (n = 20) and reversible > or = grade 3 hyperbilirubinemia (n = 4). Beneficial clinical effects were observed when imatinib was added to combination chemotherapy in patients with newly diagnosed Ph+ ALL. Further studies with larger number of patients are necessary.

The added values of multiplex reverse transcriptase-PCR followed by mutation screening in the initial evaluation of acute leukemia.

INTRODUCTION: This study investigates the benefits of using multiplex reverse transcriptase-PCR (RT-PCR) in addition to standard karyotyping during the initial evaluation of acute leukemia. METHODS: A total of 1114 consecutive specimens from patients with acute leukemia were tested using a commercial multiplex RT-PCR kit (HemaVision, DNA Diagnostic). NPM1 and CEBPA mutations were selectively tested in acute myeloid leukemia (AML) patients with multiplex RT-PCR negativity. RESULTS: In specimens with optimal cytogenetics, the frequency of recurrent translocations was 31.3%, and cryptic translocations were detected in 2.1% of samples. The concordance rate between karyotyping and multiplex RT-PCR was 97.5%. In addition to the established functions, we demonstrated the additional benefits of multiplex RT-PCR, including successful molecular characterization, even in cytogenetically suboptimal specimens (5.7%); detection of submicroscopic aberrations (1.0%); detection of rare but potentially significant translocations or variants (2.5%); selection of AML candidates for mutation analysis (68.3%); and finally exclusion of recurrent translocations in patients with acute lymphoblastic leukemia or mixed phenotype acute leukemia (22.5%). CONCLUSION: We reconfirmed the accuracy and reliability of multiplex RT-PCR for diagnosing acute leukemia and demonstrated additional advantages of this system for the initial evaluation of acute leukemia. Thus, multiplex RT-PCR is worth considering in diagnostic testing of acute leukemias.

Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a prospective study.

Donor leukocyte infusion (DLI) alone has very limited efficacy for patients with acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic bone marrow transplantation (BMT). We, therefore, prospectively tested the efficacy of cytoreductive chemotherapy (intermediate-dose cytarabine+idarubicin+etoposide) followed immediately by G-CSF-primed DLI (Chemo-DLI) in 10 relapsed ALL patients after allogeneic BMT. Seven achieved complete remission (CR) at a median of 25 days (19-73 days) after DLI. Of these seven CR patients, only one remains alive in CR 907 days after DLI. Two CR patients died in CR of graft-versus-host disease. The remaining four CR patients relapsed at a median of 153 days (120-991 days) after DLI. One is alive with leukemia at post-DLI day 1217. The median survival duration after DLI was 175 days (15-1217 days). In summary, although Chemo-DLI for relapsed ALL after allogeneic BMT induced a relatively high CR rate, durable remissions were rare. Although our data should be interpreted cautiously considering the small number of patients, these results suggest that poor outcome of DLI in relapsed ALL may be primarily due to intrinsic resistance to graft-versus-leukemia effect rather than to the rapid pace of the disease.

ESHAP plus G-CSF as an effective peripheral blood progenitor cell mobilization regimen in pretreated non-Hodgkin's lymphoma: comparison with high-dose cyclophosphamide plus G-CSF.

The ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) regimen has been shown to be effective as an active salvage therapy for lymphoma. Mobilizing stem cells following ESHAP should decrease time to transplantation by making separate mobilizing chemotherapy (MC) unnecessary, while controlling a patient's lymphoma. We therefore assessed the mobilization potential of ESHAP plus G-CSF in 26 patients (ESHAP group) with non-Hodgkin's lymphoma (NHL) and compared these results with those of 24 patients with NHL who received high-dose (4 g/m2l) cyclophosphamide (HDCY) as MC (HDCY group). The age, sex, and radiotherapy to the axial skeleton were well matched between groups, but the number of patients with poor mobilization predictors was higher in the ESHAP group. Significantly higher numbers of CD34+ cells (x 10(6)/kg) (17.1+/-18.8 vs 5.8+/-5.0, P=0.03) and apheresis day 1 CD34+ cells (x 10(6)/kg) (5.5+/-6.6 vs 1.7+/-2.0, P=0.014) were collected from the ESHAP group than from the HDCY group, and the number of patients who achieved an optimal CD34+ cell target of 5 x 10(6)/kg was higher in the ESHAP group (81 vs 50%, P=0.022). Log-rank test revealed that time to target peripheral blood progenitor cell collection (> or =5 x 10(6)/kg) was shorter in the ESHAP group (P=0.007). These results indicate that ESHAP plus G-CSF is an excellent mobilization regimen in patients with relapsed and poor-risk aggressive NHL.

Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse.

For patients with acute myeloid leukemia (AML) relapsed after allogeneic bone marrow transplantation (BMT), donor leukocyte infusion (DLI) as sole therapy has very limited efficacy. We tested the effects of cytoreductive chemotherapy, followed immediately by G-CSF-primed DLI (chemotherapy followed by DLI, Chemo-DLI), in 16 AML patients who relapsed after allogeneic BMT. In all, 10 of these patients achieved complete remission (CR), four of whom remain alive in CR at a median follow-up of 1488 days after DLI. The 2-year overall survival (OS) for the entire cohort was 31%. The 1-year OS for patients with post-BMT remission of 6 months or longer was 55%, compared with 0% for patients with post-BMT remission of less than 6 months, making post-BMT remission duration the only significant prognostic factor for OS (P=0.015). These findings suggest that Chemo-DLI could induce durable remissions in a proportion of relapsed AML patients with relatively long post-BMT remission duration. All five patients who relapsed after achieving CR with Chemo-DLI relapsed at extramedullary sites in the presence of continuous bone marrow remission, suggesting uneven graft-versus-leukemia effects in different parts of the body. Although our data should be interpreted cautiously considering the limited number of patients, isolated extramedullary relapse seems to be common after Chemo-DLI.

Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome.

We retrospectively studied 227 patients with MDS (1) to identify the prognostic factors of survival and acute leukemia evolution in Korean patients with MDS, (2) to apply different prognostic scoring systems to the same group of patients, and (3) to compare the FAB with the WHO classification. Six scoring systems were applied to the patients, and the FAB and WHO classifications were compared. The patients' median age was 57 years. The median survival time was 21 months, and age, dysgranulopoiesis and the IPSS cytogenetic groups were independent prognostic factors for survival. Acute leukemia occurred in 34 patients, and the cumulative incidence was 27.1% at 3 years. Marrow blast percentage was the only independent prognostic factor for acute leukemia evolution. Most scoring systems successfully discriminated risk groups for survival and acute leukemia evolution, but patient distribution into risk groups varied according to the scoring systems. Refractory cytopenia with multilineage dysplasia and RAEB II seemed to have different prognoses from RA or RARS and RAEB I, respectively. In summary, our MDS patients had different disease natures from those of Western countries regarding clinical features, prognostic factors and cytogenetic profiles. Although the WHO classification seems to improve the FAB classification, further studies are warranted to validate the utility of the WHO classification before it is accepted for routine clinical use. Our study has the limitations of retrospective analysis, and our results should be verified in future prospective studies.

Body fluid cellular analysis using the Sysmex XN-2000 automatic hematology analyzer: focusing on malignant samples.

INTRODUCTION: The majority of previous studies on body fluid (BF) mode of automatic hematology analyzer used nonmalignant BF samples. Here, we evaluated the BF mode on the recently launched Sysmex XN for counting blood cells, especially for malignant samples. METHODS: A total of 405 BF specimens including 125 malignant samples were analyzed using both the automated method and manual microscopy. RESULTS: In non-cerebrospinal fluids (CSF) samples, there was an agreement between two methods for WBC, RBC, polymorphonuclear, and mononuclear cell counts (R(2)  = 0.96, 0.94, 0.88, and 0.88, respectively). CSF samples showed slightly poorer correlations than other fluids. Exclusion of malignant samples significantly improved correlations in non-CSF samples, but not in CSF samples. High fluorescence-BF (HF-BF) cells were identified significantly more frequently in malignant samples compared to benign samples (17.8 and 4.15/100 WBC, respectively; P < 0.001). Receiver operating characteristic curve analysis demonstrated an HF-BF cell AUC of 0.791 using a cutoff value of 6.9/100 WBC for detecting malignant samples. CONCLUSION: The BF mode on the Sysmex XN could be an alternative method for the manual counts in the BF analysis with a few drawbacks. However, if a concentration of HF-BF cells is greater than the given threshold, microscopic examination should be subsequently performed.

Phylogenetic analysis of reverse transcriptase in antiretroviral drug-naive Korean HIV type 1 patients.

To study whether genotypic antiretroviral resistance testing (GART) is needed to guide initial antiretroviral therapy in Korea, we determined partial pol sequences in peripheral blood mononuclear cells (PBMCs) obtained from 29 antiretroviral drug-naive HIV-1 patients. Phylogenetic analysis revealed four subtypes: B (23 patients), D (1 patient), recombinant strain (2 patients), and "untyped" (3 patients). Eighteen (78.3%) of the 23 subtype B isolates formed a distinct monophyletic cluster. The average genetic distances of 23 subtype B compared with reference strain HXB2 were 2.7% (range, 1.5-4.6%). Only one patient harbored variant virus containing a V179D mutation causing resistance to efavirenz. These data derived from therapy-naive patients suggest that potential use of primary resistance testing to guide initial antiretroviral therapy should be considered in Korea. This is the first report on the molecular nature of HIV-1 RT in Korea.

Effect of increasing serum albumin on plasma D-dimer, von Willebrand factor, and platelet aggregation in CAPD patients.

This study was performed to investigate the interrelation between blood albumin level and D-dimer (a marker of intravascular coagulation) and von Willebrand factor (vWF; a marker of endothelial injury) levels or platelet aggregation. Blood levels of albumin, D-dimer, vWF, and C-reactive protein (CRP) and the threshold aggregating concentration (TAC) of ristocetin were measured in 64 continuous ambulatory peritoneal dialysis (CAPD) patients and compared with 36 healthy controls. Twenty-two CAPD patients with albumin levels less than 3.0 g/dL were divided into experimental and disease-control groups. In the experimental group, levels were measured before and after repeated infusions of 20% albumin, 100 mL/d for 7 days. The same parameters were measured in the disease-control group that did not receive the albumin infusion. CAPD patients had higher D-dimer and vWF levels than the healthy controls. There were inverse correlations between albumin and D-dimer (r = -0.48; P < 0.001), vWF (r = -0.29; P < 0.05), or logCRP (r = -0.44; P < 0.001) in CAPD patients. There were positive correlations between logCRP and D-dimer (r = 0.38; P < 0.01) and between logCRP and vWF (r = 0.32; P = 0.01) in CAPD patients. No change was seen in D-dimer, vWF, and CRP levels in either group. The TAC of ristocetin in the 18 CAPD patients was not different from that in the 11 healthy controls (0.55 +/- 0.09 v 0.65 +/- 0.07 mg/mL). There was a correlation between albumin level and TAC in the CAPD patients (r = 0.59; P < 0.01). TAC increased from 0.50 +/- 0.09 to 0.62 +/- 0.13 mg/mL (123% +/- 17%; P < 0.05; n = 6) at the end of the repeated albumin infusions in the experimental group, whereas it did not change in the control group. CRP level did not change in either group. The results of this study indicate that hypoalbuminemia increases platelet aggregability. The observation that the albumin infusion was not associated with changes in D-dimer and vWF despite the inverse correlations suggests that these relationships may be secondary to other factors, such as inflammation.

Effects of fixed low-dose warfarin on hemostatic factors in continuous ambulatory peritoneal dialysis patients.

Increased coagulation factors found in dialysis patients may explain in part the high prevalence of thrombotic cardiovascular disease. Several studies showed low-dose warfarin is effective in decreasing coagulation factors and preventing thrombosis without increasing the risk of bleeding. To evaluate the effects of fixed low-dose warfarin therapy on thrombogenesis in continuous ambulatory peritoneal dialysis (CAPD) patients, 76 CAPD patients were assigned randomly to treatment and disease control groups. The treatment group received 2 mg of warfarin daily for 12 months. International normalized ratio (INR) of the prothrombin time and plasma levels of factor VII, D-dimer, von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) were measured before and 3, 6, and 12 months after the start of medication. The same parameters were measured in 30 healthy volunteers at the beginning of the study and in the disease control group during the study period. Of 76 patients, 60 completed the study. Deaths from atherosclerotic cardiovascular disease (cerebral infarction or acute myocardial infarction) occurred in 1 patient in the treatment group (n = 29) and 3 in the disease control group (n = 31), which was not statistically significant. No major bleeding occurred during the study period. With administration of warfarin, there was a small increase in INR in the treatment group. CAPD patients at baseline had significantly higher plasma factor VII, D-dimer, vWF, and PAI-1 levels than normal controls. Warfarin therapy lowered plasma factor VII and D-dimer levels. No change was seen in vWF and PAI-1 levels. In the disease control group, these hemostatic factors showed no change during the study period. There was a negative correlation between serum albumin and INR in the treatment group during the study period. Fixed low-dose warfarin was effective in partially reversing the thrombogenic coagulation profile in CAPD patients without a big increase in the risk of bleeding.

Lack of familial clustering of hepatitis C virus infection.

BACKGROUND: Although transmission of hepatitis C virus (HCV) through parental exposure is well documented, it is still controversial whether familial clustering of HCV occurs. METHODS: To investigate risk factors for HCV infection, 109 cases and 84 non-infected controls were studied. In addition, 250 family members (104 men, 146 women) of cases and 170 family members of controls (64 men, 106 women) were tested for HCV infection using an anti-HCV antibody, alanine aminotransferase (ALT), and reverse transcribed polymerase chain reaction (RT-PCR). RESULTS: In the case-control analysis, people aged > or =60 were almost three times more likely to be infected by HCV than those aged <40. Risk of HCV infection was most strongly related to a history of blood transfusion (OR = 12.6, 95% CI: 4.3-36.5) followed by a history of jaundice (OR = 4.1, 95% CI: 1.3-12.6). Only one family member of cases and no-one related to the controls had HCV infection. CONCLUSIONS: These results suggest that, in Korea, age and parenteral exposure, such as a blood transfusion, are risk factors for HCV infection and familial clustering of HCV infection, if it occurs, is rare.

Relevance of proteins C and S, antithrombin III, von Willebrand factor, and factor VIII for the development of hepatic veno-occlusive disease in patients undergoing allogeneic bone marrow transplantation: a prospective study.

Factors that enhance hypercoagulability following BMT may have a pathogenetic role in VOD. To investigate the relevance of hemostatic parameters for the development of VOD, we prospectively measured protein C, protein S, antithrombin III (AT III), von Willebrand factor, and factor VIII in 50 consecutive patients undergoing allogeneic BMT. Each parameter was determined before conditioning, on day 0 of BMT and weekly for 3 weeks, and patients were monitored prospectively for the occurrence of VOD. VOD occurred in 26 patients at median post-BMT day 8.5 (range, day -2 to 17). Thirteen patients had mild, 10 had moderate and three had severe VOD. No coagulation parameters were significantly different at the baseline or on day 0 of BMT between patients with no/mild VOD and moderate to severe VOD. On day 7 and thereafter, levels of protein C and AT III were significantly lower in patients with moderate to severe VOD when compared to patients with no/mild VOD. Levels of protein C and AT III decreased before the clinical onset of VOD in patients with moderate to severe VOD. Early post-BMT reduction of these parameters may indicate the development of moderate to severe VOD.

Peri-engraftment clinical abnormalities following allogeneic hematopoietic cell transplantation: a retrospective review of 216 patients.

To evaluate the significance of clinical abnormalities occurring during the peri-engraftment period following allogeneic hematopoietic cell transplantation (HCT), we retrospectively analyzed the data of 216 allogeneic HCT recipients. The most frequently observed peri-engraftment clinical abnormality (PECA) was noninfectious fever in 58 patients, followed by hepatic dysfunction in 39, weight gain in 22, and renal insufficiency in 11. Frequently identified predictive factors for a higher incidence of each PECA were HCT from an unrelated or mismatched donor, GVHD prophylaxis with cyclosporine alone, and rapid engraftment. Considering that donor type and GVHD prophylaxis are closely related to GVHD, these observations suggest that the development of PECAs might be associated with a graft-versus-host reaction. This hypothesis was supported by the fact that the patient group with each PECA showed a higher incidence of grades 3-4 acute or chronic extensive GVHD, with varying degrees of statistical significance. Although our data should be interpreted cautiously in view of their retrospective nature, some of the PECAs occurring after allogeneic HCT may be atypical manifestations of GVHD and may be associated with severe forms of acute or chronic GVHD.

Veno-occlusive disease of the liver after allogeneic bone marrow transplantation for severe aplastic anemia.

There are few reports about the occurrence of hepatic VOD after BMT for severe aplastic anemia (SAA). We prospectively studied 17 patients with SAA after allogeneic BMT for the occurrence and severity of VOD. Plasma levels of protein C, protein S, antithrombin III, vWF, t-PA and PAI-1 were determined before preparative chemotherapy, on the day of marrow infusion, and on days 7, 14 and 21. VOD occurred in seven patients (41.2%) at a median of day 1 (range, day -2 to 15). Five had mild, and two moderate VOD. Platelet transfusion requirements were higher in the patients with VOD. The plasma levels of natural anticoagulants such as protein C, free protein S and antithrombin III decreased significantly on day 0 from the baseline levels. Plasma levels of t-PA, PAI-1 and vWF increased significantly in the early post-transplant period compared to the baseline levels. The mean plasma levels of t-PA on day 7 (P = 0.016) and PAI-1 on days 0 and 7 (P = 0.016, 0.032) were higher in the patients with VOD. In summary, we observed hypercoagulability and a high incidence of VOD after allogeneic BMT for SAA. Levels of t-PA and PAI-1 were significantly higher in the patients with VOD after BMT.

Prognostic value of hematopoietic chimerism in patients with acute leukemia after allogeneic bone marrow transplantation: a prospective study.

Hematopoietic chimerism as a predictive marker for the relapse of acute leukemia after allogeneic BMT was evaluated in a prospective study. Monthly assays of hematopoietic chimerism were performed from peripheral blood samples by PCR amplification of short tandem repeats or amelogenin loci. Between December 1997 and June 1999, 33 patients enrolled and 30 were evaluable (two early deaths, one lack of informative bands for chimerism evaluation). There were 14 male and 16 female patients (15 AML and 15 ALL) with a median age of 31 years (range 16-46). Mixed chimerism (MC) was observed at least once in 14 of 30 patients (47%). There was no significant difference between 14 patients who showed MC (MC group) and 16 patients who did not show MC (complete chimerism (CC) group) in terms of age, sex, disease status at BMT, donor type, and the number of bone marrow cells infused. There was no significant difference in the neutrophil and platelet engraftment rates between the two groups. After a median follow up of 10.9 months (range 4.3-22.4), five patients in the CC group and two patients in the MC group relapsed (P = 0.27). All five patients who relapsed in the CC group maintained CC up to 1 month prior to clinical relapse. Our study demonstrated that the patients who showed MC post BMT did not have higher risk of relapse of acute leukemia when compared to patients who did not show MC. Sensitive PCR-based assays for hematopoietic chimerism applied on a monthly basis after allogeneic BMT could not predict relapse of acute leukemia.

Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course.

A total of 118 consecutive adult patients with acute leukemia (78 AML, 36 ALL, and four acute mixed lineage leukemia) underwent allogeneic hematopoietic cell transplantation (HCT) after conditioning with BuCy (n=113) or a nonmyeloablative regimen of busulfan-fludarabine (n=5). After a median follow-up of 35.8 months (range, 6.4-91.0), 34 patients experienced at least one episode of leukemia relapse. Of 34 initial episodes, 14 (41%) occurred in extramedullary sites, with (n=8) or without (n=6) concomitant bone marrow involvement. The median time to relapse in the extramedullary sites was longer than that of relapse in bone marrow only (13.5 vs 6.1 months, P=0.046). Acute leukemia subtype and disease status at HCT showed an independent predictive value for overall relapse, as well as for extramedullary relapse with or without bone marrow involvement (Philadelphia chromosome positive acute leukemia vs low-risk AML, relative risk 22.68 (95% CI, 2.18-235.64); other than first CR vs first CR, relative risk 5.61 (95% CI, 1.80-17.51)), but not for bone marrow relapse. Our study suggests that there may be different pathogenetic mechanisms for bone marrow vs extramedullary relapse of acute leukemia after allogeneic HCT. The mode of relapse needs to be investigated in future reports of acute leukemia treated with allogeneic HCT.

Monthly prospective analysis of hematopoietic chimerism after allogeneic hematopoietic cell transplantation.

SUMMARY: Hematopoietic chimerism (HpC) was assayed monthly using a sensitive, polymerase chain reaction (PCR) -based method in consecutive patients. Between January 1998 and April 2002, 181 patients underwent non-T cell depleted allogeneic hematopoietic cell transplantation (HCT). A total of 163 patients were evaluable for HpC at 1 month (11 early deaths; no informative band for HpC analysis/no genomic DNA in seven). In all, 53 of 163 patients (33%, median recipient DNA of 15% (range 5-95)), 39 of 151 patients (26%), and 27 of 142 patients (19%) showed mixed chimerism (MC) at 1, 2, and 3 months after HCT, respectively. Conditioning regimen (busulfan-fludarabine-ATG vs BuCy, relative risk 3.99 (95% CI 1.16-10.92)), neutrophil engraftment (>/=day 17 vs /=5% recipient DNA at 1 month. Five patients experienced secondary graft failure. All five patients showed MC at 1 month with median recipient DNA of 40%. None of the 109 patients with complete chimerism experienced graft failure (P=0.002). Our study showed that MC shown on monthly analysis of HpC after allogeneic HCT is a significant predictor of secondary graft failure. Bone Marrow Transplantation (2003) 32, 423-431. doi:10.1038/sj.bmt.1704147