Ph-positive Cases Research Articles

Center effect on allogeneic hematopoietic stem cell transplantation outcomes for B-cell acute lymphoblastic leukemia

This nationwide study retrospectively examined the center effect on allogeneic hematopoietic stem cell transplantation (allo-HSCT) for adult B-cell acute lymphoblastic leukemia. The cohort analyses were separated into Philadelphia chromosome (Ph)-positive and -negative cases. The patients were divided into low- and high-volume groups according to the number of allo-HSCTs at each facility. The primary endpoint was 5-year overall survival (OS). This study included 1156 low-volume and 1329 high-volume Ph-negative and 855 low-volume and 926 high-volume Ph-positive cases. In Ph-negative cases, 5-year OS was significantly higher in the high-volume centers at 52.7% (95% confidence interval [CI]: 49.9–55.5) versus 46.8% (95% CI: 43.8–49.7) for the low-volume centers (P < 0.01). Multivariate analysis identified high volume as a favorable prognostic factor (hazard ratio [HR]: 0.81 [95% CI: 0.72–0.92], P < 0.01). Subgroup analysis in Ph-negative cases revealed that the center effects were more evident in patients aged ≥40 years (HR: 0.72, 95% CI: 0.61–0.86, P < 0.01) and those receiving cord blood transplantation (HR: 0.62, 95% CI: 0.48–0.79, P < 0.01). In Ph-positive cases, no significant difference was observed between the high and low-volume centers for 5-year OS (59.5% [95% CI: 56.2–62.7] vs. 54.9% [95% CI: 51.3–58.3], P = 0.054). In multivariate analysis, center volume did not emerge as a significant prognostic indicator. This study showed center effects on survival in Ph-negative but not in Ph-positive cases, highlighting the heterogeneity of the center effect in allo-HSCT for B-cell acute lymphoblastic leukemia. Collaborative efforts among transplant centers and further validation are essential to improve outcomes.

Primary hyperoxaluria: Comprehensive mutation screening of the disease causing genes and spectrum of disease-associated pathogenic variants.

The primary hyperoxalurias are rare disorders of glyoxylate metabolism. Accurate diagnosis is essential for therapeutic and management strategies. We conducted a molecular study on patients suffering from recurrent calcium-oxalate stones and nephrocalcinosis and screened primary hyperoxaluria causing genes in a large cohort of early-onset cases. Disease-associated pathogenic-variants were defined as missense, nonsense, frameshift-indels, and splice-site variants with a reported minor allele frequency <1% in controls. We found pathogenic-variants in 34% of the cases. Variants in the AGXT gene causing PH-I were identified in 81% of the mutation positive cases. PH-II-associated variants in the GRHPR gene are found in 15% of the pediatric PH-positive population. Only 3% of the PH-positive cases have pathogenic-variants in the HOGA1 gene, responsible to cause PH-III. A population-specific AGXT gene variant c.1049G>A; p.Gly350Asp accounts for 22% of the PH-I-positive patients. Pathogenicity of the identified variants was evaluated by in-silico tools and ACMG guidelines. We have devised a rapid and low-cost approach for the screening of PH by using targeted-NGS highlighting the importance of an accurate and cost-effective screening platform. This is the largest study in Pakistani pediatric patients from South-Asian region that also expands the mutation spectrum of the three known genes.

Deep Learning for Laryngopharyngeal Reflux Diagnosis

(1) Background: Deep learning has become ubiquitous due to its impressive performance in various domains, such as varied as computer vision, natural language and speech processing, and game-playing. In this work, we investigated the performance of recent deep learning approaches on the laryngopharyngeal reflux (LPR) diagnosis task. (2) Methods: Our dataset is composed of 114 subjects with 37 pH-positive cases and 77 control cases. In contrast to prior work based on either reflux finding score (RFS) or pH monitoring, we directly take laryngoscope images as inputs to neural networks, as laryngoscopy is the most common and simple diagnostic method. The diagnosis task is formulated as a binary classification problem. We first tested a powerful backbone network that incorporates residual modules, attention mechanism and data augmentation. Furthermore, recent methods in transfer learning and few-shot learning were investigated. (3) Results: On our dataset, the performance is the best test classification accuracy is 73.4%, while the best AUC value is 76.2%. (4) Conclusions: This study demonstrates that deep learning techniques can be applied to classify LPR images automatically. Although the number of pH-positive images used for training is limited, deep network can still be capable of learning discriminant features with the advantage of technique.

Different Effects of Pre-transplantation Measurable Residual Disease on Outcomes According to Transplant Modality in Patients With Philadelphia Chromosome Positive ALL.

Background: This study compared the effects of pre-transplantation measurable residual disease (pre-MRD) on outcomes in Philadelphia chromosome (Ph)-positive ALL patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical SCT (haplo-SCT).Methods: A retrospective study (n = 202) was performed. MRD was detected by RT-PCR and multiparameter flow cytometry.Results: In the total patient group, patients with positive pre-MRD had a higher 4-year cumulative incidence of relapse (CIR) than that in patients with negative pre-MRD (26.1% vs. 12.1%, P = 0.009); however, the cumulative incidence of non-relapse mortality (NRM) (7.4% vs. 15.9%, P = 0.148), probability of leukemia-free survival (LFS) (66.3% vs. 71.4%, P = 0.480), and overall survival (OS) (68.8% vs. 76.5%, P = 0.322) were comparable. In the MSDT group, patients with positive pre-MRD had increased 4-year CIR (56.4% vs. 13.8%, P < 0.001) and decreased 4-year LFS (35.9% vs. 71.0%, P = 0.024) and OS (35.9% vs. 77.6%, P = 0.011) compared with those with negative pre-MRD. In haplo-SCT settings, the 4-year CIR (14.8% vs. 10.7%, P = 0.297), NRM (7.3% vs. 16.3%, P = 0.187) and the 4-year probability of OS (77.7% vs. 72.3%, P = 0.804) and LFS (80.5% vs. 75.7%, P = 0.660) were comparable between pre-MRD positive and negative groups. In subgroup patients with positive pre-MRD, haplo-SCT had a lower 4-year CIR (14.8% vs. 56.4%, P = 0.021) and a higher 4-year LFS (77.7% vs. 35.9%, P = 0.036) and OS (80.5% vs. 35.9%, P = 0.027) than those of MSDT. Multivariate analysis showed that haplo-SCT was associated with lower CIR (HR, 0.288; P = 0.031), superior LFS (HR, 0.283; P = 0.019) and OS (HR, 0.252; P = 0.013) in cases with a positive pre-MRD subgroup.Conclusions: Our results indicate that the effects of positive pre-MRD on the outcomes of patients with Ph-positive ALL are different according to transplant modality. For Ph-positive cases with positive pre-MRD, haplo-SCT might have strong graft-vs.-leukemia (GVL) effects.

Abstract 2428: Genetic aberrations in the DNA repair pathway among children with Philadelphia chromosome positive leukemias

Abstract Background. Aberrations in the DNA repair pathway among children with leukemia are largely unknown. Knowledge of such mutations may improve the understanding of tumorigenesis, direct patient care, and enable genetic counseling of patients and families. Germline aberrations of the DNA-repair machinery are crucial for generating chromosomal instability and occurrence of acute leukemia in children. In order to better understand this mechanism, we studied a specific subgroup of childhood leukemia, e.g. t(9;22) or chromosome Philadelphia positive (Ph+) acute lymphoblastic and chronic myeloid leukemias. We addressed our research to specific genes (Nijmegen Breakage Syndrome (NBS1) and Fanconi Anemia) involved in the DNA repair pathway, in the attempt to identify mutations and aberrant expressions, predisposing and/or cooperating with the leukemogenic process. Materials and Methods. We analyzed diagnostic and remission samples of 12 children: 8 with a Ph+ acute lymphoblastic leukemia (ALL) and 4 with a chronic myeloid leukemia (CML) diagnosed and treated at our institution from 1999 to 2013. We performed RT-PCR analyses to detect mutations in exons 3-6 of the NBS1 gene, followed by a direct sequencing analysis (BMR - Padova - Italy). The status of FANCD2 and PALB2 genes was studied by a multiplex ligation-dependent probe amplification (MLPA) using the Salsa MLPA P057-025R FANCD2-PALB2 Probemix and SALSA MLPA EK1 kit (MRC-Holland, Amsterdam, the Netherlands). Samples from five healthy donors (HDs) were used as wild-type controls. For data elaboration, we used Coffalyser.Net software for MLPA. Moreover we performed a real-time PCR amplification of BRCA1 (exons 14-15) and BRCA2 (exons 15-16) genes, respectively, calculating the median fold-changes (MFC) in patients comparing with HDs. Results. We detected the NBS1 E185Q polymorphism (c533G&amp;gt;C, rs1805794) in both diagnostic and remission samples in 3 out of 12 children with a Ph positive acute leukemia (2 ALL, 1 CML). We also found two pairs of deletions in FANCD2 (Δ32-35; Δ35-38) and PALB2 (Δ2; Δ2-6) in 4 out of 12 Ph positive cases (2 ALL and 2 CML). These aberrations were mutually exclusive. Thus a total of 7 cases (58%) showed an aberrant pathway. Moreover we determined that the MFC of BRCA1 expression among children with Ph positive ALL and CML was slightly higher than HDs (1,388 vs 0,433 and 1,625 vs 0,451, respectively). Surprisingly the MFC of BRCA2 expression was strongly higher than HDs in both children with Ph positive ALL (5,924 vs 0,002) and CML (54,504 vs 0,256). Conclusion. Our preliminary findings strongly suggest that germline mutations or deletions in association with aberrant expression of specific genes that regulate the DNA repair machinery may contribute to the chromosomal instability in children with Ph positive leukemias. These data will be confirmed in a larger population of different subtypes of pediatric leukemia. Citation Format: Nellina Andriano, Paola Bonaccorso, Valeria Iachelli, Manuela La Rosa, Emanuela Cannata, Luca Lo Nigro. Genetic aberrations in the DNA repair pathway among children with Philadelphia chromosome positive leukemias. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2428.

A Two-Year Follow-Up Of a Prospective Study Of Intensified Conditioning Regimen With High-Dose-Etoposide Allogeneic Hematopoietic Stem Cell Transplantation For Adult Acute Lymphoblastic Leukemia In China

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a major role for improving the outcome of adult acute lymphoblastic leukemia (ALL), especially for high-risk and refractory/relapsed patients. Intensified conditioning allo-HSCT is based on the hypothesis that intensifying condition regimen could overcome resistance, reduce tumor burden, and most importantly, spare enough time for slow-growing graft-versus-leukemia (GVL) effect and immune reconstitution to finally get rid of minimal residual disease (MRD). Patient and Methods A single-center, open-label, prospective study of intensified conditioning regimen with high-dose-etoposide allo-HSCT for adult ALL in China was performed from 2011 to 2013 in Nanfang hospital according to HDE-ALL-2011 (NCT01457040). Results A total of 97 patients were enrolled, including 36 female and 61 male, a median age of 25 years old (range 11-54). The molecular cytogenetics make-up consisted of 33 Ph-positive cases, 2 cases of MLL-rearranged cases. Of the whole cohort, 34 of 97 cases (35.1%) were refractory and/or relapsed patients. Forty-seven patients (48.4%) received HLA-matched sibling allo-HSCT, 26 patients (26.8%) underwent HLA-matched unrelated donor transplantation, 13 patients (13.4%) received HLA-haploidentical allo-HSCT and 11 patients (11.3%) received HLA-mismatched sibling transplantation. Ninety-four patients (96.9%) achieved complete engraftment and full-donor chimerism with a median of 14 days for neutrophils (0.5G/L) and 15 days for platelet (20G/L) and three patients failed to obtain engraftment. Forty patients (40.0%) received a median of 1 time (range 1-4) pre-emptive and/or MRD-guided donor lymphocyte infusion (DLI) from 2 or 3 months after transplantation. Acute III-IV grade graft-versus-host disease (GVHD) occurred in 15 patients, including 4 cases of DLI-induced GVHD, as 9 cases occurred in matched-sibling allo-HSCT group (9/47, 19.1%), 3 cases in MUD allo-HSCT (3/26, 11.5%) and 3 cases in HLA-haploidentical/mismatched allo-HSCT group (3/24, 12.5%). Twelve patients with III-IV GVHD attained durable complete remission with cyclosporine A, tacrolimus, methylprednisolone, cyclophosphamide, methotrexate, anti-CD25 antibody and mesenchymal stem cells (MSC). The overall incidence of EBV viremia was 23.7% (n=23) and 47.8% percent (n=11) of 23 patients received rituximab preemptive therapy. Six patients (6.2%) developed EBV-related post-transplant lymphoproliferative disorders (PTLD) and durable complete remission was achieved after integrated treatment with reduction in immunosuppression, rituximab-containing chemotherapies and donor-lymphocyte-infusion. CMV viremia occurred in 23.7% patients and 6 patient progressed to CMV-related interstitial pneumonia (IP, n=6), which accounted for 27.2% of transplantation-related mortality (TRM), followed by 18.2% of rapidly progressive brochiolitis obliterans (BO) after donor lymphocyte infusion (n=4), severe GVHD (n=3, 13.6%), diffuse alveolar hemorrhage(n=2, 9.1%), sinusoidal obstruction syndrome/venoocclusive disease (SOS/VOD, n=2, 9.1%), engraftment dysfunction (n=1, 4.5%), mitochondrial encephalopathy (n=1, 4.5%), thrombotic microangiopathy (TMA, n=1, 4.5%), infection (n=1, 4.5%) and myocardial infarction (n=1, 4.5%). With 2 year of Kaplan-Meier estimate of potential follow-up (KM-PF), 9 out of 97 patients relapsed after transplantation and died of primary disease. The 2-year overall survival of the whole cohort was 60.1%, with no significant difference (p=0.624) between patients in complete remission (59.3%) and refractory/relapsed patients (61.5%) before transplantation. Conclusions Intensified conditioning regimen with high-dose-etoposide allo-HSCT (HDE-ALL-2011) yielded a promising result, especially for high-risk and refractory/relapsed ALL, but it still deserves a better optimal balance between immuno/myelo-suppression and EBV/CMV-related complications, DLI and DLI-related side effects to reduce TRM. Disclosures: Zhou: Guangzhou Pearl River of Science &amp; Technology New Star (No. 2011J2200069 to HS.Zhou): Research Funding. Liu:It was supported by 863 Program (No. 2011AA020105), National Public Health Grand Research Foundation (Grant No. 201202017): Research Funding; National Natural Science Foundation of China (Grant No.81000231, No.81270647) and Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

Results of Second Generation Tyrosine Kinase Inhibitor Frontline Therapy in Chronic Myeloid Leukemia with Variant Philadelphia Chromosome

AbstractAbstract 3774 Background:Variant Philadelphia (Ph) chromosomes are observed in 5–10% of patients (pts) with CML, involving one or more additional chromosomes besides 9 and 22. Deletions of derivative chromosome 9 (del der (9)) occur in 10–15% of pts, and frequently these abnormalities coexist. Prior to the advent of TKIs pts with variant Ph or del der (9) had a worse outcome. With imatinib the adverse prognosis conferred by these abnormalities has been minimized. To our knowledge there are no published reports regarding the outcomes of pts with variant Ph or del der(9) while on treatment with a 2nd generation TKI as initial therapy for CML. We analyzed the significance of these abnormalities among patients with CML in chronic phase (CP) enrolled in 2 parallel trials of dasatinib or nilotinib as initial therapy. Patients and Methods:A total of 205 pts with CML in CP treated between 2005 and 2012 at our institution with frontline dasatinib or nilotinib based protocols were included in this analysis. Among them 193 (94%) had classic Ph chromosome, and 12 (6%) had a variant Ph chromosome. Nineteen of the 205 pts (9%) had del der (9). Their characteristics and outcomes were compared. Results:Only one additional chromosome was present in the Ph rearrangement in each of the variant Ph-positive cases. The additional chromosomes found were 17 in three patients and chromosomes 1, 3, 4, 5, 9, 11, 14, 19, 21 in one patient each. Del der (9) was found in 2 of 12 pts with variant Ph and in 17 with classic Ph. Five (50%) of the pts with variant Ph were treated with dasatinib and 5 (50%) with nilotinib. Of those with classical Ph 93 (48%) were treated with dasatinib and 100 (52%) with nilotinib. The median age was 48 yrs (range 17 to 86) for those with classic Ph, and 53 yrs (24 to 79) for those with variant Ph. The Sokal risk group for those with classic Ph was high in 16 (8%), intermediate in 53 (28%), and low in 124 (64%). For the patients with variant Ph risk classification was 10%, 50% and 40%.No significant differences were observed in response to therapy between pts with variant Ph and those with classic Ph (CCyR 100% vs. 93%; MMR 100% vs. 85%, respectively), or between those with del der (9) and those without it (CCyR 100% vs. 93%; MMR 100% vs. 84%). The 3-year probability of overall survival (OS) was 99% for pts with classic Ph and 89% for those with variant Ph. Corresponding values for 3-year event-free survival (EFS) were 96% and 89%, and transformation-free survival (TFS) 99% and 100% respectively. 3-year OS, EFS and TFS were also similar between pts with del derv (9) and those without it (Table 1). Among the 2 pts with concomitant variant Ph and del der (9), one achieved CCyR at 3 months and has maintained it with 12 months of follow up. The second one achieved CCyR but became pregnant during the course of treatment; the TKI was temporarily discontinued and she lost cytogenetic response, but regained response after 3 months of reinitiating TKI therapy and delivering a healthy baby. Conclusion:The presence of variant Ph chromosome or del der (9) does not affect the clinical characteristics or outcome of pts with CML CP treated with second generation TKI as initial therapy.Table 1Outcomes in Variant Ph-positive patients treated withVariant PhClassic PhDel. Der. 9No Del. Der. 9Overall CCyR100%93%100%93%Overall MMR100%85%100%84%12 mo. CCyR88%97%100%96%12 mo. MMR81%50%79%93%3 years O.S.89%99%99%100%3 years EFS89%96%96%100%3 years TFS100%99%99%100% Disclosures:Kantarjian:Pfizer: Research Funding; Ariad: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding. Jabbour:Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Cortes:Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding.

Frequency and Diversity of Variant Philadelphia Chromosome In Chronic Myeloid Leukemia Patients

Abstract 4903The Philadelphia chromosome (Ph), t(9;22), is detected in around 90% of the chronic myeloid leukemia (CML) patients, but in the remaining 5–10% cases a variant type may be present. Variant Ph-chromosome is characterized by the involvement of another chromosome in addition to the 9 and 22. It can be a simple type of variant when one more chromosome is involved, or complex, in which two or more chromosomes take part in the translocation. The aim of this report is to relate the diversity of variants Ph found in CML patients at the Cytogenetic service of Fleury Lab (São Paulo, Brazil) during the past 12 years. All Ph-positive CML patients (ALL&AML were excluded) were surveyed and the variant Ph ones were listed. All the karyotype analysis were from non-stimulated short term cultures of bone marrow or peripheral blood and classified according to ISCN (1999-2009). Of the 1,071 Ph-positive cases, 967 were classic Ph, while 50 (5.17%) were variants. Regarding the variant form, 44 (88%) were simple type and 6 (12%) complex type (table 1), similar to Marzocchi et al (2011), who found 93% and 7% of each type, respectively. Some of the variant Ph translocations we detected are listed in table 1. In agreement with what Marzocchi et al reported, the most involved chromosome was the 17 (eleven times in the present report and four cases in theirs), followed in frequency by the chromosome 1 (six times), 20 (five times), 6, 11 (four times each), and 2, 10, 12 and 15 (three times each). The chromosomes not involved in the Ph translocation were: 8, 9, 18, 21, 22, X and Y (Figure 1). Among all breakpoints seen in this survey, six were repeated: 11p15, 14q32, 15q11.2, 16p13.1, 17p13 e 17q21, differing from Marzocchi et al who denied finding any recurrent breakpoint. Reid et al. (2003) listed nine recurring breakpoints in variant Ph translocations most reported by other authors, who also assert that most of breakpoints related to variant Ph occur in regions of known oncogenes or typical secondary breakpoints in other cancers. Indeed we endorse this statement, since we also found some breakpoints related to other cancers. Of the list Reid et al reported, three were found in this study as well: 12p13, 17p13 and 17q21. Some of the genes located in these regions are related to other cancers (i.e. ETV6, CD9, RARA, GAS7). However, the gene TP53, located in the region 17p13 was the only one previously reported as related to CML. Oliver M. (2007) states that this gene is involved in 20–30% of cases of blast crisis CML. Regarding the prognosis, evolution of the disease and response to the treatment, it seems that variant type of Ph translocation has no implication for survival (Marzocchi et al 2011 and Maha et al 2004. In conclusion, as we presented a large variety of variant Ph translocations, it becomes clear that there are lots of possible interactions to form variant type and most of them occur in regions already reported as oncogenes or related to cancers, indicating that there must be local phenomena favoring the predisposition to these breakpoints involvement.Table 1–Examples of variant Ph karyotypes found in this survey, showing a little of the diversity of interaction.Karyotype46,XY,t(1;9;22;16)(q32;q34.1;q11.2;p13)[2]/46,XY46,XX,t(9;22;1;13)(q34.1;q11.2;p12;q34)[17]/46,XX[3]46,XY,t(9;22;1;?3)(q34.1;q11.2;q36.3;?q26)[20]46,XX,t(1;9;22;14)(p21;q34.1;q11.2;q32)[20]46,XY,t(9;22;2)(q34.1;q11.2;q24)[8]/46,XY[12]46,XY,t(9;22;4)(q34.1;q11.2;p16)[20]46,XY,t(9;22;5)(q34.1;q11.2;p13)[20]46,XY,t(9;22;6)(q34.1;q11.2;q22)46,XX,t(9;22;7)(q34.1;q11.2;p22)[20]46,XY,t?(9;22;10;11)(q34.1;q11.2;q22;q25)[20]46,XY,t(9;22;12)(q34.1;q11.2;p13)[20]46,XY,t(9;22;14)(q34.1;q11.2;q32)[19]/46,XY[1]46,XY,t(9;22;15)(q34.1;q11.2;q11.2)[20]46,XX,t?(9;22;16)(q34.1;q11.2;p13.3)[20]46,XY,t(9;22;17)(q34.1;q11.2;p13)[20]46,XY,t(9;22;19)(q34.1;q11.2;q11.2)[20]46,XY,t(1;7)(p22;q22),t(9;22;20)(q34.1;q11;q11.2)[2]/46,XY[18] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Clinical Significance of the Philadelphia Chromosome Positive Pediatric Acute Lymphoblastic Leukemia in Chinese.

Objective To explore the incidence, clinical characteristics and prognosis of childhood acute lymphoblastic leukemia (ALL) with t(9; 22).Methods All of the clinical characteristics of the 325 childhood ALL patients from November, 1998 to November, 2003 were analysised. The statistics was done by SPSS 10.0.Results There were 129 cases of high-risk ALLs in 325 Childhood ALL patients, with 95 males and 34 females. BCR-ABL fusion gene was found in 16 cases by RT-PCR, accounting for 4.9%. All of them were m-BCR-ABL. There were 12 males and 4 females among 16 Ph positive ALLs. The mean age at diagnosis was 8.54±3.36 (3.5 to 12.5) years, 50.0% of which were older than 10 years. The percents of patients who had initial WBC count more than 100×109/L, myeloid antigen coexpression, hypodiploidy, and ALL-L2 were 37.5%, 53.8%, 33.3%, and 62.5%, respectively. By comparison, the percents of age (older than 10 years), initial WBC count (more than 100×109/L), myeloid antigen coexpression, prednisone poor response (PPR), and CR over 35 days in the Ph positive ALLs were higher than that in the negative ALLs. No statistic difference was found in sex and L2 proportion between them. Moreover, no difference was found between Ph positive ALLs and negative high-risk ALLs in the mentioned parameters, except for the myeloid antigen coexpression. Four-year event-free survivals (EFS) and disease-free survivals (DFS) were 77.4% and 79.4, respectively, in Ph negative ALLs, but were 33.0% and 47.7%, respectively, in Ph positive ALLs (P<0.01). In Ph negative high-risk ALLs, the four-year EFS and DFS were 51.2% and 54.6%, respectively, both of which had no statistic difference between Ph positive cases. Only one Ph positive child received allogeneic BM transplantation, who remained in EFS at the time of this analysis.Conclusion The percent of t(9; 22) in Chinese childhood ALLs had no difference with the report abroad. There were statistic differences between Ph positive and negative childhood ALLs in age, initial WBC count, early response to therapy, and four-year EFS and DFS, but no difference was found between Ph positive ALLs and Ph negative high-risk ALLs, except for the immunophnotype. Aggressive treatment, such as high-dose chemotherapy with allogeneic BM transplantation should be considered for these patients to improve survival. [Display omitted]

Acute lymphoblastic leukemia. Survey of immunophenotype, French-American-British classification, frequency of myeloid antigen expression, and karyotypic abnormalities in 210 pediatric and adult cases.

Immunophenotypic studies are essential to distinguish acute lymphoblastic leukemia (ALL) from minimally differentiated acute myeloid leukemia (AMLM0) and to classify ALL into immunologic subtypes. Frequently, immunophenotyping identifies myeloid antigen expression in ALL, causing a potential diagnostic problem. To evaluate the immunophenotype of ALL, we studied 210 cases of pediatric and adult ALL by flow cytometry and compared the results with the French-American-British (FAB) Cooperative Group classification and the karyotypic findings. Myeloid-associated antigens were expressed in 78 (45.6%) of precursor B-cell ALL cases. Pediatric precursor B ALLs had a higher frequency of myeloid antigen expression than did adult cases. All mature B-cell ALL cases were negative for TdT and myeloid antigens. Myeloid antigen expression was less frequent in T-cell ALL cases compared with precursor B-cell ALL cases. Of the 192 cases submitted for cytogenetic analysis, 147 were abnormal. The most common chromosomal translocation was the Philadelphia chromosome, which was more likely to have L2 blast morphology and a precursor B immunophenotype. Myeloid antigen expression was present in 70.8% of Ph-positive cases (P = .008). Chromosome rearrangements involving 11q23 also showed an increased frequency of myeloid antigen expression. Chromosome translocations involving regions of T-cell receptor genes were present in 24% of T-cell ALL cases. A high percentage of ALL cases, however, had various other cytogenetic abnormalities, many of which involved less well-studied chromosomal regions.