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[Clinic and immunophenotypic studies on midline malignant histiocytosis].

OBJECTIVE: To understand the clinic opatholgic changes of midline malignant histiocytosis (MMH), and to explain the source of atypical lymphoid cells (ALC) of MMH, so as to search after the relation between MMH and malignant lymphoma. METHOD: Histopathologic section of 39 cases of MMH were taken HE staining and the histopathologic changes were obsered under microscope. The immunohistochemical staining was also used to examine the immunophenotype of ALC. RESULT: 1. Pathologic changes of MMH: coaglation necrosis and mixed inflammatory cells infiltration, with epithelial infiltration which distributed around the center of blood vessel were their characteristics. 2. Immunohistochemical staining result: 28 in 39 cases of MMH (71.8%) expressed the immunophenvtype of T-cell; among them 13 (33.3%) were finded both positive reaction to CD3 and CD57 antigens with ALCs at the same time. CONCLUSION: According to immunophenotypic studies, most ALCs came from proliferation and infiltration of atypical T cell. ALCs of MMH expressed not only T-cell markers (CD3), but also NK-associated antigen (CD57). MMH was a mucosa related peripheral T/NK cell lymphoma originally.

Adult↗

[Immunophenotype of acute leukemia and its clinical significance].

OBJECTIVE: To examine the immunophenotype of adult acute leukemia and analyze its clinical significance. METHODS: Immunophenotypes were examined by direct immunofluorescence method and flowcytometry in 69 de novo AL. RESULTS: 1. The incidence of myeloid antigen expression in 29 adult ALL was 30%. Among them, CD13 was 10.3% and CD33 was 20.7%, no difference was found in expression of myeloid antigens between B-ALL and T-ALL (P > 0.05). Myeloid antigens were expressed much more higher in CD34 positive ALL than in CD34 negative ALL (77.8% vs 13.3%, P = 0.036). CR rate in myeloid antigen positive ALL was lower than in myeloid antigen negative ALL (33.3% vs 80%, P = 0.0203). 2. The incidence of lymphoid antigen expression in 40 adult AML was 30%. Among them, CD7 was 15%, CD19 12.5% and CD2 2.5%. CD7 was mainly expressed in M1 and M2 subtypes. Lymphoid antigens were expressed higher in CD34 positive AML than in CD34 negative AML (61.1% vs 4.5%, P = 0.000125). Though CR rate was lower in lymphoid antigen positive AML than in lymphoid antigen negative AML, no significant difference between them was noted (50% vs 71.4%, P = 0.126). CONCLUSION: Aberrant antigen expression in adult acute leukemia is about 30%. Antigen aberrant is much higher in CD34 positive AL than in CD34 negative AL. The CR rate of antigen aberrant AL is lower than that of usual AL.

Adolescent↗

[Analysis of immunophenotype of B-lineage acute lymphoblastic leukemia cells by 4-color flow cytometry].

To investigate the characteristics of immunophenotype of B-lineage acute lymphoblastic leukemia (B-ALL) cells in Chinese cases, B-ALL cells from 181 patients were analyzed by 4-color flow cytometry with CD45/SSC gating. The results demonstrated that the antigen expression frequencies were as follows: CD19 (100%), HLA-DR (98.9%), CD38 (88.5%), CD10 (76.8%) and CD34 (76.8%). CD117 and T antigens (CD2 and CD7) were rarely expressed. Childhood group ( or= 19 years) had a higher expression rate of myeloid antigens (CD13 and/or CD33). Subtype CD10(+)/CD34(+) took the highest percentage in three age groups. Percentages of CD10(-)/CD34(+) group increased by age. Subtype CD10(-)/CD34(+) had the highest myeloid antigen co-expression. Comparing with CD45-positive cases, those with CD45-negative or CD45(+/-) always had higher CD10 expression. Bcr/abl mRNA was evaluated in 43 samples from patients with B-ALL. Myeloid antigen co-expression was not different in bcr/abl(+) and bcr/abl(-) groups, and m-bcr/abl(+) was mainly observed in subtype CD10(+)/CD34(+). In conclusion, typical B-ALL cells expressed CD19(+), HLA-DR(+), and CD117(-). CD34, CD10 and CD45 expression varied in different maturation stages. The immunophenotypic subtype of B-ALL in adolescents was similar to that in the adults. Blasts with CD45(+) were mostly seen in CD10(-) cases. CD13 and/or CD33 co-expression was fewer in children patients. m-bcr/abl(+) was mainly seen in subtype CD10(+)/CD34(+).

Adolescent↗

[Immunophenotypic features of bcr/abl fusion transcript-positive B-lineage acute lymphoblast leukemia].

To investigate the biological features of leukemic cells in bcr/abl fusion transcript-positive B-lineage acute lymphoblastic leukemia (B-ALL), 3- or 4-color flow cytometry with directly conjugated monoclonal antibodies was used to detect the immunophenotype of the cells in 26 patients with bcr/able-positive B-ALL and 32 patients with bcr/abl-negative B-ALL. bcr/abl fusion transcript was detected by RT-PCR. Immunoglobulin heavy chain (IgH) gene rearrangement was detected by PCR. The results showed that all of the B-ALL patients were positive for CD19. There was significant difference in expression of CD34 (96.2% vs 65.6%), CD10 (96.2% vs 71.8%) and CD38 (43.8% vs 95.4%) between bcr/abl-positive and -negative groups. In bcr/abl-positive B-ALL group, the co-expression rates of CD10(+)/CD19(+)/CD34(+), CD10(+)/CD34(+)/HLA-DR(+) and CD10(+)/CD34(+)/CD38(-) were 92.3% (24/26), 73.1% (19/26) and 56.2% (9/16), respectively. In bcr/abl-negative group, co-expression of CD10(+)/CD19(+)/CD34(+) and CD10(+)/CD34(+)/HLA-DR(+) were 43.8% (14/32) and 37.5% (12/32), respectively, there were significant differences (P < 0.05) between bcr/abl-positive and -negative groups, but none of the cases co-expressed CD10(+)/CD34(+)/CD38(-). The detection rate of monoclonal IgH gene rearrangement (58.8%, 10/17) was lower in bcr/abl-positive group than that (85.7%, 12/14) in bcr/able-negative group. It is concluded that the expression rates of CD34 and CD10 are higher, and CD38 and IgH gene rearrangement are lower in bcr/abl-positive B-ALL cases, CD10(+)/CD34(+)/CD38(-) is a unique feature of immunophenotype, and this phenotype of leukemia cells is closer to that of early B-lineage progenitor cells.

Adolescent↗

Utility of flow cytometry immunophenotyping and DNA ploidy studies for diagnosis and characterization of blood involvement in CD4+ Sézary's syndrome.

BACKGROUND AND OBJECTIVES: The exact immunophenotypic criteria for the identification of Sézary cells in the blood are still poorly defined. DESIGN AND METHODS: We analyzed the immunophenotype and DNA cell content of blood T cells in a series of 18 consecutive cases of Sézary's syndrome (SS), 21 normal individuals and 10 patients with reactive erythroderma, and correlated them with molecular and morphological findings. RESULTS: Phenotypically abnormal CD3+/TCRalphabeta+/CD4+ T cells were found in all SS patients but in none of the reactive erythroderma cases; small diploid, or less frequently hypodiploid Sézary's cells coexisted with large nearly tetraploid Sézary's cells in some cases. The most frequent phenotypic aberrations consisted in decreased expression of CD3/TCRalphabeta (94%), CD4 (94%), CD7 (100%) and/or CD2 (83%). In addition, Sézary's cells were constantly CD28+ and CD5+ and they did not express natural-killer associated (NKa) antigens. Phenotypic heterogeneity was a common finding and phenotypic changes over time were frequently observed. In contrast to what was found in patients with reactive erythroderma, flow cytometry analysis of the T-cell receptor (TCR) repertoire revealed a major TCR-Vbeta expansion in all SS cases. INTERPRETATION AND CONCLUSIONS: The presence of CD28+/CD5+/NKa-/CD4+ T cells expressing abnormally low levels of CD3, TCRalphabeta, CD4, CD7 and/or CD2 would support the diagnosis of SS in patients with erythroderma. Further analyses on larger series of patients are necessary in order to cover less frequent phenotypic patterns, establish the preferential usage of specific TCR-Vb families and investigate the specificity of these phenotypic abnormalities for diagnosing SS.

Adolescent↗

Immunophenotypic analysis of peripheral blood stem cell harvests from patients with multiple myeloma.

BACKGROUND AND OBJECTIVES: Four-color multiparameter immunophenotyping has recently proven to be an attractive technique for evaluating the plasma cell (PC) compartment since it allows discrimination between myelomatous and normal PC. This study was designed to investigate: i) whether peripheral blood is less contaminated than bone marrow as a source for an autologous transplant; ii) the effect of growth factors on mobilizing myelomatous PC into peripheral blood; iii) the degree of contamination by myelomatous PC in apheresis samples; and iv) whether the number of PC increases during the last days of apheresis. DESIGN AND METHODS: Using 4-color antigen staining we investigated the composition of the PC compartment in 90 apheresis products from 40 patients with MM; in 17 cases bone marrow and peripheral blood samples were also simultaneously evaluated. RESULTS: (i) All pre-mobilization bone marrow samples analyzed were always contaminated with myelomatous PC whereas only 41% of the post-mobilization peripheral blood samples were contaminated. Moreover, the use of peripheral blood would lead to a reduction of >5x10(5) infused myelomatous PC; (ii) mobilization with cytokines increased the number of circulating PC, generally because of an expansion of the normal PC population; (iii) forty-eight percent of all peripheral blood stem cell harvests were contaminated with myelomatous PC, although normal PC usually represented the predominant population; (iv) no significant changes were observed in the amount of contaminating myelomatous PC during the first three days of apheresis. INTERPRETATION AND CONCLUSIONS: Multiparameter immunophenotyping is a useful approach for investigating the PC compartment in apheresis products.

Adult↗

Flow cytometric detection of rare normal human marrow cells with immunophenotypes characteristic of acute lymphoblastic leukemia cells.

Rare subpopulations of normal marrow B lymphoid cells expressing immunophenotypes typically found in B-lineage acute lymphoblastic leukaemias (ALL) were sought by multiparameter flow cytometry. First, CD34+ marrow leukocytes were isolated by immune adherence using immunomagnetic microspheres, and analyzed for coexpression of the following pairs of membrane antigens: CD34 CD22; CD34 CD20; and CD10 CD22. Terminal deoxynucleotidyl transferase expression was not assessed. All three antigen combinations were found on small percentages of the CD34-enriched cell population. Second, unseparated normal low density marrow leukocytes were examined by 'gating' on cells with the right-angle light scatter of lymphoid cells, plus either CD34+ or CD10+ immunofluorescence. This independent approach confirmed that rare subsets of normal cells coexpress 'immature' and 'mature' differentiation antigens. In addition, remission marrow cells were examined from two children who had completed therapy for ALL two and four months earlier. Both specimens had a more than threefold increase in CD34+ cells over normal marrow, and cells coexpressing immature and mature cell surface antigens were easily detected. These findings demonstrate that immunophenotypes characteristic of B-lineage ALL, previously labeled 'asynchronous' with respect to the developmental sequence of the majority of normal B lymphoid cells, exist at low frequency in normal human bone marrow.

Antigens, CD↗

Haematologic and immunophenotypic profile of acute myeloid leukemia: an experience of Tata Memorial Hospital.

OBJECTIVES: To study the hematologic and immunophenotypic profile of 260 cases of acute myeloid leukemia at diagnosis. MATERIAL AND METHODS: This is a retrospective analysis of 260 cases of AML diagnosed at our institution between 1998 and 2000. Diagnosis was based on peripheral blood and bone marrow examination for morphology cytochemistry and immunophenotypic studies. SPSS software package, version 10, was used for statistical analysis. RESULTS: Seventy-six percent of our cases were adults. The age of the patients ranged from one year to 78 years with a median age of 27.2 years. There were 187 males and 73 females. The commonest FAB subtype, in both children and adults, was AML-M2. The highest WBC counts were seen in AML-M1 and the lowest in AML-M3 (10-97 x 10(9)/L, mean 53.8 x 10(9)/L). The mean values and range for hemoglobin was 6.8 gm/l (1.8 gm/l to 9.2 gm/l), platelet count 63.3 x 10(9)/L (32-83 x 10(9)/L), peripheral blood blasts 41.4% (5 to 77%) and bone marrow blasts 57.6% (34-96%). Myeloperoxidase positivity was highest in the M1, M2 and M3 subtypes. CD13 and CD33 were the most useful markers in the diagnosis of AML. CD14 and CD36 were most often seen in monocytic (38%) and myelomonocytic (44%) leukemias. Lymphoid antigen expression was seen in 15% of cases. CD7 expression was the commonest (11%). CONCLUSION: AML accounted for 39.8% of all acute leukemias at this institution. The most common subtype was AML-M2. Myeloperoxidase stain was a useful tool in the diagnosis of myeloid leukemias. CD13 and CD33 were the most diagnostic myeloid markers.

Adolescent↗

[Complex histologic, immunophenotypic and molecular genetic investigation in cutaneous T-cell lymphoproliferative diseases].

Diagnosis of cutaneous T-cell lymphomas, especially of mycosis fungoides is often difficult in the early stage of the disease, as well as their differentiation from other reactive inflammatory dermatoses. The diagnostic exactness could be improved by the simultaneous histological, immunophenotypic and gene rearrangement analysis of the skin biopsy specimen, and these results together with the clinical findings could help to establish the early diagnosis. Using this complex analysis effective treatment can be started in time and repeated skin biopsies are not always necessary. Authors performed this complex investigation in skin biopsy specimens and peripheral blood of 49 patients with cutaneous T-cell lymphoma and other T-cell lymphoproliferative diseases and estimated the diagnostic value of the T-cell receptor gamma gene rearrangement analysis. Based on the results of the clinical, histological, immunophenotypic and gene rearrangement studies authors could made a clear distinction between the benign dermatoses (19 cases) and malignant cutaneous lymphomas (17 cases). However less than one third of the patients (13 cases) remained unclassified, so definite diagnosis of these cases could be based on the long term follow up and on the results of the repeated skin biopsies.

Adult↗

[Importance of immunophenotyping in the diagnosis of B-cell lymphoproliferative diseases ].

The immunophenotyping of the lymphoproliferative diseases is considered to be an integral part of the diagnostic process pointing to the correct classification of the individual diseases and to the choice of the most suitable type of therapy. This article describes the immunophenotype of particular types of B-lymphoproliferative disorders included in the World Health Organization classification (WHO) and the prognostic importance of some markers. The panel of specific monoclonal antibodies directed to B-cell lineage used in our department is displayed.

B-Lymphocyte Subsets↗

Immunophenotypic profile of adult acute myeloid leukemia (AML): analysis of 267 cases in Thailand.

Little data exists in Thailand and other Southeast Asian countries regarding the biological characteristics of adult acute myeloid leukemia (AML). In this study, we performed a flow cytometric analysis of 267 Thai adult AML cases to delineate the pattern of leukemic cell surface antigens. Forty-eight cases (18%) were identified as acute promyelocytic leukemia (M3) and 219 cases as non-M3. The most frequent subtype of AML in Thailand was M1/M2 and the least frequent was M7. M3 immunophenotypes were characterized by their unique lack of expression of CD34 and HLA-DR as contrast to the high mean expression of 50% and 70%, respectively, in non-M3. Overall, 60% of cases expressed CD34. Aberrant lymphoid antigens were uniquely seen in specific subtypes of Thai AML, including CD19 (33% of non-M3 vs 23% of M3) and CD2 (12% of M3 vs 2% of non-M3). CD56 was frequently expressed in both M3 and non-M3 while CD16 appeared to be associated with M4/M5 (24% of cases) and CD7 with M1/M2 (21% of cases). Eighty-one percent of non-M3 expressed CD38 while only 53% of M3 did. We found that most Thai adult AML patients were on average 15-20 years younger than those of the West or Japan with only 25% of Thai cases over 60 years of age, although the immunophenotypes were not markedly different. Biological studies of acute leukemia in various countries should help to provide epidemiological clues that play a role in the pathogenesis of leukemia in different geographic regions of the world. Our study represents the largest series of AML ever investigated in the Southeast Asian region.

Acute Disease↗

Determination of laboratory reference ranges for lymphocyte immunophenotype subsets in healthy adult Japanese using flow cytometry.

This study represents a comprehensive evaluation of normative values for lymphocyte immunophenotype subsets using flow cytometry techniques in a Japanese population. Lymphocyte reference ranges were determined for percentage and absolute count of T, B, and NK cells in healthy adult Japanese using an extensive two-color immunophenotyping panel and consistently applied quality control methodology. Reference values were also determined for activation markers on CD3+ lymphocytes CD3+/CD25+, CD3+/CD38+ and CD3+/HLA-DR+. Differences in age and gender were observed for specific lymphocyte subsets. Comparison of the Japanese study with a Thai multi-center study that used similar methodology also demonstrated ethnic differences in lymphocyte reference ranges. The results in this study strongly suggest that reference values derived from studies in one population may not be applied to another population even when similar protocols for reagents, instruments and procedures are used although such studies do appear useful for epidemiological comparisons.

ADP-ribosyl Cyclase↗

[Immunophenotype of peripheral blood mononuclear cells in atopic diseases].

According to the different theories considering the role of CD30 antigen in the differentiation of T lymphocytes, the aim of this study was to analyze the immunophenotype of peripheral blood mononuclear cells (PBMC) in patients with mild atopic asthma and seasonal allergic rhinitis in out of season period. The immunophenotype of peripheral blood mononuclear cells (CD4, CD38, CD8, CD23, CD25, CD57, CD30, HLA-DR) was analyzed by flow-cytometry. A statistically significant rise in the percentage of CD30+ PBMCs in asthma group (3.50 +/- 2.07%) was seen when compared with allergic rhinitis group (1.80 +/- 0.90%). In allergic rhinitis patients a significant rise in the percentage of CD8+ lymphocytes (13.21 +/- 5.87%) was observed in comparison to asthma group (8.36 +/- 5.88%). No statistically significant differences in the expression of the other estimated molecules were detected. The enhancement of CD30 molecule expression on PBMCs in symptomatic asthma is supposed to confirm, due to Romagnani's theory, the predominance of Th2-type response in the pathogenesis of immunoinflammation active phase. PBMCs from patients with allergic rhinitis in out-of-season period may switch into cytotoxic/suppressive cells, confirmed by rise in the percentage of CD8+.

Adolescent↗

[Usefulness of monoclonal antibodies for immunophenotyping in leukemia].

Clinically useful monoclonal antibodies, applied for immunophenotyping of leukemias, are reviewed. With a combination of 15 antibodies, including CD2, CD3, CD4, CD5, CD7, and CD8 for T cell marker analysis, CD10, CD19, CD20, surface immunoglobulins, and cytoplasmic mu chain for B cell marker analysis, CD13 and CD33 for myeloid marker analysis, and HLA-DR and CD25 for other marker analysis, acute lymphoblastic leukemias of T cell type, cALL type, pre-B cell type and B cell type, acute myeloid leukemias, acute unclassified leukemias and adult T cell leukemias could be clearly diagnosed by immunophenotyping of cell membrane molecules. By using additional CD11b, CD14, and CD15 monoclonal antibodies, subclassification of acute myeloid leukemia was partially possible.

Antibodies, Monoclonal↗

Cluster analysis of apoptosis-associated bcl2 family proteins in diffuse large B-cell lymphomas. Relations with the apoptotic index, the proliferation profile and the B-cell differentiation immunophenotypes.

BACKGROUND: There is evidence that apoptotic mechanisms mediated by bcl2 family proteins are involved in the pathogenesis of diffuse large B-cell lymphomas (DLBCL). In order to gain further insight into the apoptosis profile of DLBCL, 79 cases were investigated to determine whether distinct clusters of the combined expression levels of bcl2 family proteins can be identified in these lymphomas. MATERIALS AND METHODS: The combined immunohistochemical expression levels of the proteins bax, bak, bad, bid, bcl2 and bcl-xl were evaluated by cluster and discriminant analysis. The produced clusters were analyzed in relation to the apoptotic index, the proliferation profile and the B-cell differentiation immunophenotypes. RESULTS: Cluster analysis produced: a) a low expression (69/79 cases) and a high expression pro-apoptotic cluster (10/79 cases) for the combined expression levels of the pro-apoptotic proteins bax, bak, bad and bid and b) a low expression (37/76 cases) and a high expression antiapoptotic cluster (39/76 cases) for the combined expression levels of anti-apoptotic proteins bcl2 and bcl-xl. The decreasing order of discriminant power for the percentages of tumor cells expressing pro-apoptotic and anti-apoptotic proteins was % bax + cells> % bak+ cells> % bid+ cells> % bad+ cells and % bcl2+ cells> % bcl-xl+ cells, respectively. The high expression pro-apoptotic cluster was significantly associated with higher mean values of Ki67 (p=0.047) and cyclin A (p=0.033) expression. The high expression pro-apoptotic cluster was significantly associated with the germinal center B-cell bc16/CD10/MUM1/CD138 differentiation immunophenotype (p=0.043). CONCLUSION: This study identified distinct clusters of DLBCL with respect to the combined expression levels of the apoptosis-associated bcl2 family proteins. These findings, taken together with our previous observations that distinct clusters with respect to the apoptotic index and the proliferation profile are identified in DLBCL, indicate that subgroups with distinct cellular kinetic properties can be defined in these lymphomas. The cluster analysis approach might be useful for the identification of subgroups of DLBCL with different clinical behavior since increased proliferation and apoptosis were reported to be associated with aggressive tumor behavior in these lymphomas.

Apoptosis↗

Combined immunophenotyping and DNA in situ hybridization to study lineage involvement in patients with myelodysplastic syndromes.

Clonality of myeloid and lymphoid cell fractions obtained from peripheral blood (PB) or bone marrow (BM) of five patients with a myelodysplastic syndrome (MDS), was studied by combined immunophenotypic analysis and DNA in situ hybridization. This novel technique enables quantitative and direct analysis of cytogenetic alterations in nondividing cells of distinct cell lineages. Four patients with a trisomy 8 and one patient with a translocation (1;7) were studied. For cell lineage determination, antibodies specific for progenitor cells (CD34), myeloid cells (CD15), monocytes (63D3), T cells (CD3), and B cells (CD19,20,22) were used. In one patient with a trisomy 8, BM cells were available and the erythroid lineage could be studied. For detection of cytogenetic aberrations, we used chromosome-specific repetitive DNA probes. In three patients, all nonlymphoid cells carried the cytogenetic abnormality; in two patients, mosaicism within these lineages was suggested by the relative low numbers (35% to 55%) of aberrant cells. None of the T or B cells of the five patients carried the chromosomal aberrations. We conclude that combined immunophenotyping and in situ hybridization is a feasible technique to study lineage involvement. Our data suggest that the chromosomal aberrations studied in MDS are restricted to the myeloid lineages.

Adult↗

Three-color flowcytometric analysis of mature and immature hematological malignancies. A guideline of the Dutch Foundation for Immunophenotyping of Hematological Malignancies (SIHON).

Multiparameter flowcytometry offers an insight into differentiation pathways, maturation stages and abnormal features of cell (sub)populations thus helping to establish and classify hematological malignancies. The Dutch Foundation for Immunophenotyping of Hematological Malignancies (SIHON) has formulated a guideline for a rapid screening followed by confirmation and classification in a standardized way. For this aim seven carefully composed monoclonal antibody combinations are elucidated for screening the test sample in a first phase. In this phase a relative frequency distribution of the cells will be established and a decision will be made about abnormal cells present, as well as their mature or immature state and the cell lineage they belong to. In a second phase, panels with cell lineage dependent monoclonal antibody combinations may be used to confirm and classify the abnormal cell population indicated in phase 1, as well as to establish the presence or absence of an abberant immunophenotype.

Flow Cytometry↗

Current results of studies of immunophenotype-, age- and leukocyte-based therapy for children with acute lymphoblastic leukemia. The Pediatric Oncology Group.

From February 1986 to January 1991 the Pediatric Oncology Group (POG) treated 2404 children or adolescents with acute lymphoblastic leukemia (ALL) on immunophenotype (T-, B-, Pre-B, or Early pre-B-cell), age, and leukocyte count based treatment protocols (ALinC 14, T-cell 3, B-cell and infant leukemia studies). The immunophenotypic subgroups comprised 78.9% B-precursor cell, 15.1% T-cell, 2.0% B-cell, and 4% infant ALL. Patients with B-progenitor cell ALL were stratified by age and leukocyte count and randomized to receive induction therapy comprised of vincristine, prednisone, and asparaginase with triple intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine), followed by intensification with moderate-dose MTX (Regimen A), moderate-dose MTX plus asparaginase (Regimen B), moderate-dose MTX plus cytarabine given early (Regimen C), or moderate-dose MTX plus cytarabine given over the first 16 months of therapy (Regimen D). Continuation therapy comprised mercaptopurine and methotrexate with vincristine plus prednisone pulses. Central nervous system preventive treatment was continued for two years. Patients with T-cell or B-cell ALL or infants less than 1 yr old were treated on individual very intensive multiagent therapy protocols. The 4-year event-free survival for all patients was 66.4% +/- 2.4%; B-precursor ALL approximately 72%, T-ALL approximately 50%, B-ALL approximately 60%, and infants less than 1 yr old approximately 16.5%. We conclude that about two-thirds of newly diagnosed children with ALL can be cured with this approach which spares the majority of children exposure to alkylating agents, anthracyclines, epipodophylotoxins, and irradiation, diminishing the risks of serious acute and late effects.

Adolescent↗