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Query: UMLS:C0023418 (leukemia)
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Chimerism analysis has become a routine method to document engraftment and also for detection of residual disease. PCR-based procedures using STR analysis, especially commercially available multiplex assays, are frequently used. However, these assays have been optimized for forensic purposes and do not necessarily fulfil all needs for chimerism analysis. To improve these analyses, data on the level of informativity of STR systems in the context of chimerism analysis would be helpful. We evaluated 27 STR markers for their informativity in 203 patients and their HLA-matched related donors. These STRs included 18 from different multiplex kits, whereas nine were selected from the literature or STR databases. The STR profiles were ranked from Type 1 (not informative) to Type 5 (best suited for chimerism analysis). According to this ranking, the informativity of the STR systems was found highly variable, ranging from 4.4 to 49.0% Type 5 constellations. Among the most informative STRs were Penta E, SE33, D2S1338 and D18S51. Informativity of an STR was correlated with the degree of heterozygosity (r=0.86; P=0.0001), but not with the total number of alleles present. These data indicate that selection of suitable STR markers is important to improve diagnostics based on STR analysis.
Leukemia 2004 Feb
PMID:Evaluation of STR informativity for chimerism testing--comparative analysis of 27 STR systems in 203 matched related donor recipient pairs. 1467 48

The main goal of post-transplantation monitoring in hematopoietic stem cell transplantation (HSCT) is to predict negative events, such as disease relapse, graft rejection and graft-versus-host disease, in order to intervene with appropriate therapy. In this context, chimerism analysis is an important method in monitoring post HSCT outcome. Mixed chimerism (MC) is mainly evaluated to define engraftment and relapse. Detection of MC is a prerequisite in both myeloablative and nonmyeloablative HSCT, in order to assess the graft status and decide later therapeutic strategies such as donor lymphocyte infusion. In this review, we discuss various techniques including erythrocyte phenotyping, cytogenetic analysis, fluorescent in situ hybridization, restriction fragment length polymorphism, STR/VNTR analysis and real-time quantitative PCR, along with the various methods used to detect minimal residual disease (MRD) in different diseases such as chronic myeloid leukemia, acute myelomonocytic leukemia or acute lymphoblastic leukemia. The review mainly highlights the optimal methodological approach, which needs to be informative, sensitive and quantitatively accurate for MC detection. Future of post HSCT graft monitoring lies in the selection of the most accurate and sensitive technique to determine both MC and MRD. Such an approach would be helpful in not only determining relapse or rejection, but also in ascertaining various responses to different treatment modalities.
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PMID:Significance of chimerism in hematopoietic stem cell transplantation: new variations on an old theme. 1515 63

In order to evaluate relapse predication ability of STR-PCR combining with qualitative RT-PCR for the bar/abl transcripts to the patient with chronic myeloid leukemia (CML) fulfilled allogeneic stem cell transplantation (allo-HSCT), 24 patients with CML after allo-HSCT were dynamically investigated for MRD, quantitative analysis of donor chimerism was performed by multiplex PCR amplification of STR markers and capillary electrophoresis with fluorescence detection, qualitative detection of bcr/abl transcripts was detected by nested RT-PCR. The results showed that persistent full donor chimerism (DC >/= 95%) was associated with an absence of MRD. All patients with stable MC (90% </= DC < 95%) and bcr/abl negative had a probability of long-term survival with molecular remission, however the result of bcr/abl positivity was not always associated with leukemia relapse, only the patient with decreasing values of donor chimerism as well as bcr/abl positive proved to be in a higher risk of relapse or graft failure. Decrease of donor chimerism in correlation with MRD positive was detected in 5 patients. Three out of five patients had been proved to have a molecular relapse, one out of five patients had developed to cytogenetic relapse and another patient experienced graft failure. It is concluded that the results of STR-PCR in the range of its sensitivity fully correspond with bcr/abl tests in patients. The combination of STR-PCR with RT-PCR will provide a highly sensitive and valuable tool for MRD detection in CML and can identify these high risk patients with molecular or cytogenetic relapse after allo-HSCT.
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PMID:[Detection of minimal residual disease of chronic myeloid leukemia patients after allogeneic stem cell transplantation by combination of STR-PCR with RT-PCR]. 1536 37

This study was aimed to observe the efficacy and side effects of allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) in patients with leukemia. The donors were siblings matched with t HLA-A, B, DR loci of recipient. After mobilization with 250 microg/day rhG-CSF for 5 days, peripheral blood stem cells were collected 1 to 2 times. 4 patients with leukemia received 6.78 x 10(8)/kg +/- 1.96 x 10(8)/kg (5 x 10(8)/kg-8.67 x 10(8)/kg) peripheral blood mononuclear cells, which contained 15.02 x 10(6)/kg +/- 8.93 x 10(6)/kg (5.3 x 10(6)/kg-24.23 x 10(6)/kg) CD34(+) cells after modified Bu/Cy conditioning regimen and MTX + CsA + MMF were given for prophylaxis of aGVHD. The results showed that the leukocyte was reduced to the lowest at pretransplantation 2 days-posttransplantation 2 days. Neutrophil amount >0.5 x 10(9)/L was found at 11 - 17 day after transplantation, platelet >50 x 10(9)/L-at 11 - 55 days after transplantation. Out of 4 patients, aGVHD, cGVHD and infection took place in 2,2 and 2 cases, respectively. Bone marrow displayed hematopoietic recovery at 28 day after transplantation, examination of STR in DNA revealed proliferation of donor cells in patients. In conclusion, Allo-PBSCT in combination with modified Bu/Cy conditioning regimen and MTX + CsA + MMF prophylaxis of aGVHD is safety and reliable for treatment of leukemia.
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PMID:[Treatment of leukemia by allogeneic peripheral blood stem cell transplantation from sibling donors]. 1563 69

The purpose of this study was to observe the chimera status of 15 patients received allogeneic hematopoietic stem cell transplantation by using STR-PCR method. DNA from peripheral blood or bone marrow of donors and recipients in different time were extracted, 5 STR loci with high polymorphism were amplified by PCR. The PCR products were analyzed by PAGE and silver staining. The results showed that 15 patients had different level of engraftment. 10 patients displayed complete chimerism, five patients showed mixed chimerism. 10 patients were keeping continuance of remission, 4 patients died and one patient relapsed but still alive. The decrease of donor DNA amounts in mixed chimerism foreshowed the early graft rejection or relapse. Incidence of I-II degree aGVHD high significantly correlated with mixed chimerism. It is concluded that STR-PCR is the sensitive and accurate method for analyzing the chimera status after allogeneic hematopoietic stem cell transplantation. Mixed chimerism is a prophetic role for leukemia relapse and chimera status guides the treatment.
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PMID:[Detection of engraftment evidence after allogeneic hematopoietic stem cell transplantation by STR-PCR]. 1574 30

Dendritic cells (DC) as potent antigen-presenting cells (APC) and T cells as effector cells play an essential role in the pathophysiology of both graft-versus-host (GvH) and graft-versus-leukemia (GvL) reactions after transplantation. Therefore, we determined the kinetics of DC and T-cell chimerism establishment after allogeneic hematopoietic cell transplantation (AHCT) in a group of 144 patients, using fluorescence-activated cell sorting (FACS) or magnetic cell sorting (MACS) followed by FISH or STR-PCR analysis for chimerism evaluation. In all, three cell lines investigated (CD3(+) T cells, CD11c(+) DC1 and CD123(+) DC2), we found a rapid and consistent establishment of complete donor chimerism (CDC) in over 70% of all patients during the first 6 weeks after AHCT. The rate of patients with CDC increased significantly over time within the first year after transplantation. A related donor (P=0.004) as well as an underlying lymphatic leukemia (P=0.03) were found to be significantly associated with development of MC in T cells. No significant correlation between DC or T cell chimerism and GvHD or relapse was detected. Our results thus demonstrate a fast and stable CDC in DC1, DC2 and T cells after AHCT that continuously increases over time in nearly all patients.
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PMID:Kinetics of dendritic cell chimerism and T cell chimerism in allogeneic hematopoietic stem cell recipients. 1625 29

A 34-year-old female was referred to our hospital for the evaluation of atypical lymphocytosis. Leukocyte count at diagnosis was 17,900/microl with 58% atypical lymphocytes having a convoluted nucleus and prominent nucleoli. Because the leukocyte count increased to 43,600/microl, the patient was treated with 2'deoxycoformycin followed by CHOP combination chemotherapy. However, both treatments failed to achieve remission. We planned an allogeneic bone marrow transplantation from an HLA-matched unrelated donor. The patient was treated with Ara-C and etoposide before conditioning to decrease the high leukemia burden. After administration of total body irradiation (12 Gy in six fractions) and cyclophosphamide (total dose of 120 mg/kg) unmanipulated marrow cells were infused. Under prevention of GVHD by CsA and short-term MTX, leukocyte engraft was prompt at day 16, and acute GVHD grade II was observed. Because 9.4% of residual recipient type T-cells was seen with STR analysis on day 22, we decreased the dose of Cs'A. After the occurrence of mild acute GVHD, the residual T-cell number decreased. The patient is still in complete remission for up to 22 months after BMT. We conclude that allogeneic SCT is effective for the treatment of T-PLL.
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PMID:[Allogeneic bone marrow transplantation for chemotherapy-resistant T-prolymphocytic leukemia]. 1644 Jul 47

To assess the potential contribution of major histocompatibility complex class I chain-related gene A (MICA) polymorphisms toward the pathogenesis of leukemia, 107 leukemia patients and 162 ethnically matched controls from Hunan province, Southern China, were genotyped for the MICA polymorphism using polymerase chain reaction-sequence-specific priming (PCR-SSP) and sequence-based typing (PCR-SBT). The relevance between these genotypes and risk of leukemia was assessed by means of odds ratio (OR) with 95% confidence intervals (95% CIs). Allele frequencies of MICA-sequence and MICA-STR were different in leukemia patients in comparison with normal controls (both P < 0.05). MICA A5 was directly associated with leukemia (OR = 2.3257, Pc < 0.0005), whereas MICA A5.1 and MICA*008 were inversely associated with leukemia (OR = 0.5874, Pc = 0.0235 and OR = 0.5874, Pc = 0.0329, respectively). In addition, we found that homozygotes for MICA A5 (OR = 14.0659, 95% CI: 3.1627-62.5574, Pc < 0.0001) and MICA*010 (OR = 10.1053, 95% CI: 2.2139-46.1260, Pc < 0.0004) were at an increased risk for leukemia, whereas heterozygotes for MICA*008 and MICA A5.1 were linked to a decreased risk for leukemia (OR = 0.4609, 95% CI: 0.2799-0.7590, Pc = 0.0027). MICA allelic variation is associated with leukemia in Hunan Han population; the data also suggest that MICA gene polymorphism affects susceptibility to different clinical subtypes of leukemia.
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PMID:Positive association of major histocompatibility complex class I chain-related gene A polymorphism with leukemia susceptibility in the people of Han nationality of Southern China. 2181 82

We describe the implementation of short tandem repeats-polymerase chain reaction (STR-PCR) chimerism analyses coupled with reverse transcription PCR detection of recurrent translocations characteristic for childhood leukemia in monitoring of patients after allogeneic hematopoietic stem cell transplantation in Serbia and the first clinical results thereof. Chimerism and minimal residual disease were regularly analyzed from blood and marrow samples of 26 pediatric patients taken after stem cell transplantation with a median follow-up of 17.6 months. Our results demonstrate that STR-based chimerism monitoring is sufficient in establishing the origin of engrafted cells after transplantation and in detecting graft rejection, but more specific and more sensitive method is necessary for identifying patients with threatening leukemia relapse.
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PMID:Monitoring of pediatric patients with malignant hematological diseases after allogeneic HSCT: Serbian experience. 2254 20

Human leukemia cell lines are of great value in leukemia research. In this study, we established and described the biological characteristics of a rare atypical chronic myeloid (aCML) leukemia cell line (NT-1). Mononuclear cells were isolated from the bone marrow of a patient with atypical chronic myeloid leukemia (Ph(-)/bcr(-)/abl(-)), and were passaged by liquid culture. Cells were maintained without any cytokines for over 1 year, and named NT-1. This cell line was extensively characterized using morphological assays, flow cytometry, cytogenetic analysis, clonogenic culture, quantitative fluorescent PCR, short tandem repeating sequence PCR (STR-PCR) and array-CGH. Its tumorigenic capacity was also examined in nude mice. The NT-1 cell line had morphological features of chronic myeloid leukemia and major myeloid markers (CD13, CD33, CD11b). Additionally, NT-1 expressed progenitor cells and natural killer cell-related antigens such as CD34, CD117, CD56. Cytogenetic analysis initially demonstrated two abnormalities: 47, xx, +8 and 47, xx, +8 accompanied by t(5;12)(q31;p13) translocation. The one-year passage process did not alter the karyotype. NT-1 cells maintained the same morphology, immunophenotyping and cytogenetic features as primary leukemia cells, which was strongly supported by STR-PCR results. Neither Epstein-Barr virus nor mycoplasma was detected in the NT-1 line. In addition, NT-1 cells showed high tumorigenic capacity in nude mice. NT-1 is a new atypical chronic myeloid leukemia cell line with the +8 and t(5,12) translocation, and exhibits high tumorigenicity in nude mice. This new cell line provides a useful tool for the study of leukemogenesis.
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PMID:Establishment and characterization of a rare atypical chronic myeloid leukemia cell line NT-1. 2501 64


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