Mature B-cell Acute Lymphoblastic Leukemia Research Articles

Improved Outcome of Childhood Acute Lymphoblastic Leukemia (ALL) with Induction Failure Treated on the Japan Association of Childhood Leukemia Study (JACLS) ALL F-Protocol.

With modern risk-adapted multi-agent chemotherapy, complete remission (CR) is obtained in the majority of children with acute lymphoblastic leukemia (ALL) and long-term survival free from disease can be expected in more than 70% of them. However, the prognosis of the patients without CR (induction failure; IF) has been dismal. We conducted a prospective study of F-protocol followed by a hematopoietic stem cell transplantation (SCT) in patients with IF.Purpose: To evaluate the efficacy and safety of the treatment strategy adopted in the JACLS ALL F-protocol.Patients and methods: Between April 1997 and March 2005, 1,254 patients with newly diagnosed ALL (excluding mature B-cell ALL) were enrolled on two consecutive JACLS ALL protocols (ALL-97 and ALL-02). Excluding induction death, 19 (1.6%) out of 1,207 patients with non-Ph+ ALL and 9 (30%) out of 30 patients with Ph+ ALL could not achieve CR following four- or five-drug induction chemotherapy. Among them, 25 patients in total were entered the study with guardian's written consent. F-protocol consisted of the AML oriented re-induction chemotherapy (3 days of 8 mg/m2 MIT, 500 mg/m2 CA, and 40 mg/m2 PSL, followed by 3 days of 200 mg/m2 VP16, CA, and PSL a week later), four block consolidation therapy consisting of two alternative regimens A and B (A: HD-DEX, VP16, CA, MIT, B: HD-MTX, ASP, PSL, CA, THP-ADR) and maintenance therapy. Patients with CR were scheduled to receive SCT after the second consolidation therapy before the maintenance therapy. Transplant procedures depended on the institute.Results: Following the re-induction therapy, 15 of 16 patients with non-Ph+ ALL (93.8%) achieved CR and 13 (86.7%) of them had continued CR until 27th week of treatment (CCR), which was the expected limiting time of SCT. Eight of 11 patients receiving SCT at the first CCR are alive. Two of 13 patients with CCR did not receive SCT by a physician's decision, and relapsed during maintenance therapy. However they are alive following SCT in second CR. Five-year overall survival rate (OS) and event free survival rate for all 16 cases was 53% and 32.8%, respectively. Estimated five-year OS for patients receiving SCT at the first CCR was 59.7%. On the other hand, only 3 of 9 patients with Ph+ ALL (33.3%) achieved CR. No patients without response to re-induction therapy could achieve CR by any subsequent chemotherapy, but one success with SCT. Among 3 patients attaining a CR with re-induction therapy, 2 could continue CR and underwent SCT. One is alive in CCR and the other deceased from TRM. The other patient, relapsed during consolidation therapy, underwent SCT with success. Five-year OS for all 9 patients with Ph+ ALL was 33.3%. Concerning about adverse events of F-protocol, there was only one non-hematological toxicity NCI-CTC grade 4, which was pancreatitis due to ASP.Conclusions: F-protocol could produce a high remission induction rate in non-Ph+ ALL, but not in Ph+ ALL. Improved outcome of non-Ph+ ALL patients with IF seemed to be obtained with F-protocol timely followed by SCT.

Effective Risk-Adapted Therapy for Childhood B-Precursor Acute Lymphoblastic Leukemia (ALL) with the Japan Association of Childhood Leukemia Study (JACLS) ALL-97 Protocol.

BACKGROUND: With current intensified chemotherapy, more than 70% of children with acute lymphoblastic leukemia (ALL) are curable. However, prognosis of the patients at higher risk has been unsatisfied. More appropriate risk assignment and innovative treatment is expected to be developed. We conducted a clinical trial of JACLS ALL-97 including multi-agent block therapy followed by hematopoietic stem cell transplantation (SCT) for the selected higher risk patients.PATIENTS AND METHODS: Between April 1997 and March 2002, 674 patients aged 1 to 15 years with newly diagnosed ALL (excluding mature B-cell ALL) were enrolled on the JACLS ALL-97 protocol. Excluding 75 T-ALL, 26 mixed lineage leukemia other than B-precursor ALL with myeloid markers, 9 acute unclassified leukemia and 1 B-precursor ALL with pretreatment, 563 patients with B-precursor ALL were eligible for this analysis. Treatment group was divided 5 groups according to the modified National Cancer Institute (NCI) workshop criteria. Standard risk (SR) and IR (intermediate risk) divided by WBC10 × 103 account for NCI-SR. High risk (HR) and ER (extremely high risk) divided by WBC 100 × 103 account for NCI-HR. The patients with ALL positive for Philadelphia chromosome and for translocation with chromosome11q23 were assigned to the highest risk group F. The patients in complete remission (CR) at day 35 with M2/M3 at the day 14 marrow were assigned to shift higher risk after induction therapy. Treatment of ALL-97 consists of early phase and maintenance phase. Early phase includes induction therapy, consolidation therapy, sanctuary therapy, and re-induction therapy for 19 to 26 weeks dependent on risk group. Early phase in IR/HR protocol is identical to the SR protocol except the addition of two doses of DNR and three doses of CPM. Maintenance phase contains standard MTX and MP with monthly VCR and PSL intensification for SR, and rotational therapy of a set of MTX and MP with a set of VCR, PSL, ASP, and (DNR or CPM) for IR/HR/ER/F. The IR protocol is identical to the HR protocol without cranial irradiation. Treatment duration is 24 months for any risk. The patients assigned ER and F were candidate for allogeneic stem cell transplantation by the end of early phase. Transplant procedures depended on the institute.RESULTS: Number of patients at each risk was 204 for SR, 158 for IR, 128 for HR, 36 for ER, 27 for Ph+ and 10 for 11q23. Six of them were treated with incorrect risk protocol. Thirty-four patients received SCT in first CR. Following the induction therapy, 550 of 564 patients (97.5%) achieved CR. 23 patients(8 in SR, 9 in IR, 4 in HR and 2 in ER, 4.4% of all) were shift to higher risk due to the findings of day 14 marrow. Five-year overall survival rate (OS) and event-free survival rate (EFS) for all patients was 90.6% and 77.0%, respectively. Five-year EFS for NCI-SR and HR was 81.6% and 67.6%, respectively. According to risk group, 5-year EFS for SR, IR, HR, ER, Ph+ ALL, and ALL with 11q23 were 86.6%, 77.0%, 71.9%, 68.7%, 40.7%, and 70.0%, respectively. 5-year OS for them were 94.0%, 93.9%, 92.1%, 83.8%, 55.6%, and 68.6%, respectively.CONCLUSIONS: By the risk-adapted therapy in the JACLS ALL-97 trial, high cure rate could be achieved for children with B-precursor ALL.

Outcome of a Risk-Adapted Treatment for Childhood Acute Lymphoblastic Leukemia in Thailand.

Acute lymphoblastic leukemia (ALL) is the most curable cancer in children. In developing country with limited resource and manpower like Thailand, where 3 pediatris hematologists take care of 100 new cancer children per year, it is a challenge to achieve satisfactory outcome. We treated ALL according to a risk-adapted modified CCG-105 protocols (standard or intensive induction of remission, consolidation, 1800 cGy CNS radiation, and maintenance therapy with or without delayed intensification, DI) since 1988. We reported here the outcome of childhood ALL treated with this protocol between 1997–2004. 181 children with newly-diagnosed ALL in this period were classified into B-precursor, or T-cell ALL by immunophenotyping with flow cytometry. B-precursor ALL were classified as low risk group (age 1–10 yr and initial white cell count (WBC) <20,000/μl), standard-risk (age 1–10 yr and WBC between 20,000–50,000/μl) and high-risk (age >10 yr or WBC >50,000/μl). The low-risk group were assigned to protocol B (CCG-105 standard induction without DI, n=69). The standard- and high-risk group were assigned to protocol C (CCG-105 intensive induction with DI, n=71). All T-cell ALL (n=21) were assigned to a T-cell protocol (DFCI 85-01 high-risk group) which includes high-dose methotrexate and asparaginase. Infantile ALL (n=9), mature B-cell ALL (n=3), a child with t(1;19), and 5 children who refused treatment or received other protocols of treatment were excluded from analysis. The remission rates were 98.5% for protocol B, 92.4% for protocol C, and 83.3% for T-cell disease. All remission failure were attributed to early deaths. The 5-yr event-free survival (EFS ±95% confidence interval) was 83.1 ± .7% for low-risk group treated with protocol B, 75.9 ± 6.0% for protocol C, and 68.6 ± 12.1% for T-cell ALL. These outcomes are significantly higher than our previous report. (Nuchprayoon I, Songnui T, Vanichsetakul P, Seksarn P. Treatment of childhood acute lymphoblastic leukemia in Thailand- outcome and cost analysis. Blood 96 (11 suppl 1): 435a) and can be attributed to a better risk classification, more intensified treatment for standard-risk group and T-cell ALL, and better supportive care. Satisfactory outcome of childhood ALL can be achieved in developing country with risk-adapted treatment strategy. [Display omitted]

Adult Acute Lymphoblastic Leukemia

Much progress has been made in understanding the biology of and therapy for acute lymphoblastic leukemia (ALL). This progress has translated into the recognition of several subgroups of ALL and the institution of risk-adapted therapies. New therapies are emerging based on the definition of specific cytogenetic-molecular abnormalities. Changes in the pathologic classification of ALL have led to therapeutic consequences. Adaptation of successful treatment strategies in children with ALL has resulted in similar complete remission rates in adults. Prognosis has Improved especially in mature B-cell ALL and T-cell lineage ALL. However, regardless of ALL subgroup, long-term survival in adults is still inferior to that in children. Development of new drugs and agents tailored to subset-specific cytogenetic-molecular characteristics is vital to the therapeutic success in adult ALL.

Mature B-cell acute lymphoblastic leukemia with t(9;11) translocation: a distinct subset of B-cell acute lymphoblastic leukemia

Mature B-cell acute lymphoblastic leukemia (ALL) is typically associated with the FAB-L3 morphology and rearrangement of the MYC gene, features characteristic of the leukemic phase of Burkitt's lymphoma. However, the term ‘mature’ has also been used to describe other rare cases of B-ALL with light-chain surface immunoglobulin expression. In contrast, infantile B-cell ALL is generally characterized by rearrangement of the MLL gene, an immature pro-B-cell phenotype, and CD10 negativity. We describe two unusual cases of infantile B-ALL with non-L3 morphology, expressing a mature B-cell phenotype (λ sIg+, CD19+, CD10−, TdT−, and CD34−), and showing MLL rearrangement without MYC rearrangement at presentation. Both infants relapsed after months of morphologic and genetic remission. At relapse, the t(9;11) translocation was detected in both cases by spectral karyotyping. After the initial relapse, both cases followed a rapid and aggressive course. Literature search identified few similar cases, all expressed λ surface immunoglobulin and showed MLL rearrangement (majority with the t(9;11) translocation). These cases show that B-ALL with MLL rearrangement, especially the t(9;11) translocation, can express a ‘mature’ B-cell phenotype and may represent a distinct subset. Identification of additional cases will further clarify the significance of MLL rearrangements in mature B-ALL.

Mature B-cell acute lymphoblastic leukemia with associated translocations (14;18)(q32;q21) and (8;9)(q24;p13). A Burkitt variant?

○ The translocation t(14;18)(q32;q21) is most commonly associated with follicular lymphoma but has also been described in acute lymphoblastic leukemia (ALL) of B-cell origin. Although these ALL cases have had a pre-pre-B, preB, or mature B-cell immunophenotype and L2 or L3 morphology, all have been associated with an abnormality of 8q24. In fact, 91% (10 of 11) have been associated with t(8;22) or t(8;14), marker chromosomes for Burkitt-type ALL. The other case was associated with del(8)(q24). Thus, Burkitt-type ALL may have various immunophenotypes and morphology when associated with t(14;18). We describe a case of mature B-cell ALL associated with t(14;18) and t(8; 9)(q24;p13). The morphology was suggestive but not entirely characteristic of the L3 subtype. However, on the basis of the cytogenetic findings and the review of the literature, perhaps this case represents a variant of Burkitt-type ALL, which would be important to recognize for prognostic and therapeutic purposes. We describe our findings and review the literature to heighten awareness of this group of ALLs associated with t(14;18). Additional cases need to be accrued and documented to determine the significance of an associated abnormality of 8q24 in this setting.

Non-Radiolabelled PCR Consensus Primers and Automatic Sequencing Enable Rapid Identification of Tumor-Specific VH CDR3 in Aggressive B-Cell Malignancies

Even though the results of current therapy are improved for B-cell acute lymphoblastic leukemia (B-ALL) and Burkit t's lymphoma (BL), prognosis of relapsed mature B-ALL and BL still remain extremely poor. In this study, we investigated the possibility of applying the use of non-radiolabelled PCR consensus primers and automatic sequencing for the rapid identification of the tumor-specific VH CDR3 nucleotide sequence, in mature B-ALL and BL. RNA was extracted from four consecutive, unselected samples from BL cases and three consecutive, unselected samples from mature B-ALL cases. The feasibility of the identification of the tumor-specific VH CDR3 nucleotide sequence was then assessed by using non-radiolabelled PCR consensus primers with automatic sequencing. The tumor-specific VH CDR3 nucleotide sequence was successfully identified for all seven patients (3 mature B-ALL and BL). The time required was substantially lower than that of the other methods previously published, despite the poor quality of some of the samples. The procedure showed rapidity, reliability and reproducibility. The characteristics of the methodology applied widen the possibility of developing anti-idiotypic therapeutic strategies, even in these B-cell malignancies.

Recent advances in pediatric acute lymphoblastic and myeloid leukemia.

Acute leukemia is the most common form of childhood cancer and is the primary cause of cancer-related mortality in children. In the United approximately 3250 cases are diagnosed annually in children and adolescents younger than 20 years, of whom 2400 have acute lymphoblastic leukemia (ALL). Treatment results in childhood ALL continue to improve, and the expected current cure rates approach 75 to 80% of all children with ALL, including T-ALL and mature B-cell ALL, the two variants that, not too long ago, had a considerably poorer prognosis compared with the common form of BpALL. The most significant new development in the past 2 years has been the development of further evidence for fetal origin of childhood leukemias, and additional evidence to support the notion that postnatal events modulating the events of immune-mediated elimination of these leukemic clones play a major role in the eventual development of clinical disease. Other epidemiologic developments include (1) increased appreciation of the role of drug-metabolizing enzymes, both in determining the predisposition to leukemia and response to therapy; and (2) both clinical observations and gene expression studies seeming to identify a new approach to the evaluation and treatment of children with MLL (11q23) rearrangements. A most remarkable new development in the induction therapy of childhood leukemia and lymphoma in the United States is the use of urate oxidase for prevention of tumor lysis syndrome and the associated uric acid nephropathy. Drug resistance, determined either on leukemic blast cells in vitro or by studies of MRD, is being looked at critically in an effort to improve the treatment results further. Consolidation with HDMTX has gained wider popularity with the realization that effective CNS prophylaxis can be achieved with intrathecal therapy plus HDMTX for consolidation. In contrast to ALL, the progress in the therapy of acute myeloid leukemia (AML) lags behind, with cure rates of approximately 40 to 50%. There is no convincing evidence for substitution of daunorubicin with other anthracyclines, nor evidence for using high-dose cytarabine during induction in childhood AML. Rather, a 3 + 10 regimen with total daunorubicin 180 mg/m2 and cytarabine 100 to 200 mg/2 for 10 days appears to yield the best results. The most important component of the postremission chemotherapy continues to be several courses of high-dose cytarabine. The results from the MRC 10, LAME 89/91 studies and the recent BFM 93 trial with high-dose cytarabine and mitoxantrone suggest that there may be some benefit to including this combination in the postremission phase of AML. Despite these improvements in chemotherapy, allogeneic BMT from a matched family donor remains the best option for most patients (excluding Down syndrome, APL, and possibly those with inv16). Newer prognostic markers of interest include FLT3/ITD and minimal residual disease at the end of induction therapy.

New chromosome rearrangement in acute lymphoblastic leukemia

Cytogenetic findings in leukemia can be used in the diagnosis, prognosis, and in the definition of different subgroups. The most common chromosome abnormalities associated with mature B-cell acute lymphoblastic leukemia (ALL) are t(8;14), t(8;22), t(2;8), and partial duplication of 1q. Various abnormalities involving chromosome 1 have also been reported in ALL. We present a 16-year-old male with mature B-cell ALL whose cytogenetic analysis of bone marrow showed the karyotype of 46,XY,t(8;14)(q24;q32), −15,der(1;15)(p10;q10). The case presented here carries one of the most common abnormalities, t(8;14) (q24;q32), and a new rearrangement, der(1;15)(p10;q10), which has not been described to date in mature B-cell ALL.

Management of adult acute lymphoblastic leukemia: moving toward a risk-adapted approach.

The vast majority of adults with acute lymphoblastic leukemia (ALL) now achieve remission with current intensive chemotherapy regimens. Nevertheless, most adults with ALL will eventually relapse and die of their disease. Specific clinical and molecular-cytogenetic prognostic factors have been identified that are beginning to provide insights for the development of risk-adapted management strategies that appear to improve survival for several high-risk patient groups, including those with mature B-cell ALL and B-lineage ALL patients with a Philadelphia chromosome. We review standard and some recently described prognostic factors in adult ALL, describe current therapy based on a risk-adapted approach, and look toward the future with a brief discussion of novel, targeted treatments that could be incorporated into postremission strategies to improve survival for adults with ALL.

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.

Recent advances in the biology and management of acute lymphoblastic leukemia in adults.

Acute lymphoblastic leukemia (ALL) is a malignant disease resulting from the unregulated clonal proliferation and arrested maturation of lymphoblasts. The phenotypic heterogeneity of the lymphoid neoplasia is a function of the complicated ontogeny these cells undergo in differentiation, as well as their multiplicity of activities in vivo. Evolving techniques in immunophenotyping and molecular genetics have refined our knowledge and classification of the lymphoproliferative diseases. These techniques allow lymphoid malignancies to be classified according to their specific lineage (B-or T-cell), their stage of differentiation (early pre-B, pre-B, or B-cell), and their genotype (specific translocations, oncogenes, etc.). Classifications of leukemia that rely exclusively upon morphology and histochemistry, such as the French-American-British (FAB) system, are limited by their inability to accurately stage the degree of differentiation or to identify molecular subsets of disease. These limitations do not allow adequate prognostication or risk stratification prior to the commencement of therapy. Knowledge of the lymphoblast molecular characteristics is becoming increasing important in defining new clinicopathologic correlations prior to commencing definitive therapy. Such is already the case with mature B-cell ALL (t(8;14)) and Philadelphia chromosome (t(9;22))-positive ALL.

Z-138: a new mature B-cell acute lymphoblastic leukemia cell line from a patient with transformed chronic lymphocytic leukemia

We describe a new mature B-cell acute lymphoblastic leukemia (ALL) cell line designated Z-138 that was derived from a patient with chronic lymphocytic leukemia (CLL) whose disease underwent transformation to a rare, aggressive form of mature B-cell ALL. This cell line has an L3 morphology, ultrastructural characteristics of lymphoblasts, B-lineage surface markers and an immunoglobulin heavy-chain gene rearrangement identical to the rearrangement observed in the patient's blasts from whom the cell line was derived. Z-138 cells produce granulocyte-macrophage colony-stimulating factor (GM-CSF) and high levels of granulocyte-CSF (G-CSF), but they do not exhibit a proliferative response to either cytokine. Both the patient's lymphoblasts and Z-138 cells exhibited cytogenetic abnormalities including t(8;14), t(14;18) and a chromosome 11 abnormality similar to the t(11;14) of the parental cells, resulting in marked overexpression of cyclin D1 (BCL-1 (PRAD1)) mRNA in Z-138 cells. Since these karyotypic anomalies have been associated with low grade (t(14;18)), intermediate grade (t(11;14)) and high grade (t(8;14)) lymphomas, their development may be involved in the unusual aggressive transformation of this patient's CLL.

Adult acute leukemia

Untreated acute leukemia is a uniformly fatal disease with a median survival time shorter than 3 months. Current treatment strategies provide a significant increase in survival time for most patients, some of whom may be cured. The majority of patients with acute leukemia, however, ultimately die of the disease or complications of treatment. The effective treatment of acute leukemia requires (1) differentiation of acute myeloid leukemia (AML) from acute lymphoblastic leukemia (ALL) and recognition of clinically relevant subtypes; (2) identification of patients who are more likely or less likely than average to benefit from a conventional treatment; and (3) selection of therapy that provides a reasonable likelihood of response with acceptable risk of toxic effects. The diagnosis of acute leukemia is established in most cases by a bone marrow aspirate that demonstrates at least 30% blast cells. The traditional criteria to distinguish between AML and ALL rely on morphology and cytochemical reactions. Immunologic analysis of antigen expression and analysis for numerical or structural chromosomal abnormalities of leukemia cells are routinely feasible. Karyotypic analysis is of prognostic importance and should be performed on all diagnostic specimens of bone marrow aspirate. Immunophenotypic analysis may be useful to confirm the disease classification in selected cases. The importance of the routine immunophenotypic characterization of acute leukemia, however, is controversial. The subtypes that must be recognized because of the need for specific treatment include (a) acute promyelocytic leukemia (APL), which is the M3 subtype of AML, and (b) the L3 subtype or mature B-cell ALL. Induction therapy for acute leukemia is treatment intended to achieve induction of complete remission (CR). Complete remission is defined as the absence of morphologic evidence of leukemia after recovery of the peripheral blood cell counts. Failure to achieve CR may be attributed to death during chemotherapy-induced bone marrow hypoplasia or to drug resistance manifested either as failure to achieve hypoplasia or as persistent leukemia after recovery from hypoplasia. Postremission therapy is treatment administered in CR to prevent or delay relapse of the leukemia. However, the majority of patients have disease relapse. Intensification of therapy is a treatment strategy designed to overcome resistance to chemotherapy. Recent clinical trials of intensified induction or postremission therapy suggest improved outcome. However, the toxic effects of dose intensification can be substantial, limiting any potential benefit of this approach. Identification of prognostic factors may allow one to estimate the likelihood of an outcome, to determine an optimal treatment strategy. It is well established that age at the time of diagnosis, leukemia cell karyotype, and whether the leukemia is de novo or secondary are factors that influence treatment decisions. Patients with favorable prognostic factors should probably receive conventional therapy. Patients with unfavorable prognostic factors have shown little benefit from conventional therapy. In addition, factors that indicate poor outcome with conventional therapy are also predictive of poor outcome with intensified therapy. Consequently, these patients should be considered for investigational therapeutic strategies. The bias may be to counsel them to accept the potential increased morbidity of such treatment before there is definite evidence of the possibility of improved outcome. Induction chemotherapy for younger patients with AML (less than 55 years of age) in general consists of one or more courses of cytarabine (ara-C) and an anthracycline or an anthracycline derivative. Randomized trials have failed to confirm that treatment with either etoposide or high-dose ara-C induces disease remission. Patients with secondary AML, high levels of CD34 antigen expression, or an unfavorable karyotype, however, may benefit from ind

Characterization of chromosome 8 abnormalities by fluorescence in situ hybridization in childhood B-acute lymphoblastic leukemia/non-Hodgkin lymphoma

Using fluorescence in situ hybridization (FISH), we studied chromosome 8 abnormalities in 30 children with mature B-cell acute lymphoblastic leukemia (B-ALL) or B-cell non-Hodgkin lymphoma (B-NHL). FISH was performed on metaphase spreads and interphase nuclei with a whole chromosome 8 painting probe. Fifteen patients were studied retrospectively after metaphases from the malignant cell specimen had already been G-banded. When interphase nuclei were examined, FISH was able to confirm t(8;14)(q24;q32) in all nine patients positive by previous G-banding. FISH, however, was positive in metaphase spreads from only seven patients. Another 15 patients were included in a prospective study. In six of them (40%), a translocation involving chromosome 8 was shown by a split small segment (8q24-8qter) on interphase nuclei. Analysis of metaphase spreads showed only three positive cases each by FISH or G-banding, respectively, with corresponding results in two patients. By interphase FISH, trisomy of chromosome 8 also was detectable. In three patients shown by G-banding to have trisomy, interphase FISH study showed high scores of three chromosome 8 signal positive cells. There was no cross-hybridization to other chromosomes interfering with FISH analysis. FISH analysis on interphase nuclei using a whole chromosome 8 hybridization probe will supplement and can be more sensitive than metaphase cytogenetic techniques for detection of chromosome 8 rearrangements in B-ALL/NHL.