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PubMed1996

Postirradiated and nonirradiated gliosarcoma: immunophenotypical profile.

BACKGROUND: Thirty-one gliosarcomas (25 nonirradiated and 6 postirradiated tumors) were selected based on the presence of two distinctive areas: a malignant gliomatous and a sarcomatous component. In all cases, the sarcomatous component appears like fibrosarcoma or malignant fibrous histiocytoma. Two tumors showed additional areas consisting of osteochondroid differentiation. METHODS: All tumors were examined using antibodies against Ulex europaeus agglutinin I (UEA), glial fibrillary acidic protein (GFAP), vimentin (VM), epithelial membrane antigen (EMA), desmin, collagen IV, alpha-1-antitrypsin (alpha-1-AT) and smooth muscle actin (SMA). RESULTS: While the VM highlighted the sarcomatous areas of all tumors there were only scattered spindle cells that were GFAP-positive in the same areas. The alpha-1-AT was diffusely reactive in the sarcomatous areas in 20 cases. Focal immunoreactivity was seen with SMA (20 tumors), UEA (8 tumors), EMA (5 tumors), collagen IV (5 tumors) and desmin (4 tumors) in the nonvascular sarcomatous cells. CONCLUSIONS: The range of immunophenotypical expression is likely to be a reflection of the capacity of a multipotential progenitor to undergo divergent differentiation. There is a very little morphological difference between the postirradiated and nonirradiated tumors except that a higher proportion of postirradiated tumors are immunoreactive to SMA and desmin.

Brain Neoplasms↗
PubMed2003

Immunophenotyping and T-cell proliferative capacity in a healthy aged population.

The age-related decline of immunological functions is well established but it remains largely unknown which specific changes are related to disease. We analyzed peripheral blood lymphocytes of 42 healthy elderly as well as 24 healthy young subjects from southern Brazil. No differences in phytohemagglutinin-induced proliferation and CD4:CD8 ratio were found between the subjects. However, CD4 expression (considering mean fluorescence intensity) was found upregulated in elderly subjects. No changes in activation molecules CD25, CD28, CD69 and CD95 were observed. A reduced proportion of naive (CD45RA+) T cells was found in the elderly compared to young subjects. No changes in adhesion molecule expression (CD11c and CD31) were observed. However, the frequencies of CD49d-positive cells, as well as expression of CD62L, were increased in the eldery subjects. We further described two subgroups of eldery subjects with an immunological risk profile defined by lower CD4:CD8 ratio and reduced proliferative response to mitogens. These data suggest that healthy aging is associated with intact T-cell proliferation and some compensatory immunophenotypical changes.

Adult↗
PubMed1997

Immunophenotyping of human HT29 colon cancer cell primary tumours and their metastases in severe combined immunodeficient mice.

The immunophenotype of HT29 human colon cancer cells implanted into severe combined immunodeficient mice was assessed in primary tumours and their metastases in the lungs using an indirect immunohistochemical method. After primary tumours were surgically removed, the metastases were given time to develop, thus paralleling the clinical situation. While vimentin was negative in both primary and secondary tumours, E-cadherin was present as membrane-bound labelling in the primary tumours only. Whereas the markers p53, MIB1, PCNA and CEA were consistently positive in both primary and metastatic tumours, CD44 variant 6 and CA125 were negative in metastases but positive in the primary tumours. There was a significant increase in the percentage of cells labelled for p53 in the primary tumours compared with the metastases. For the proliferation markers, there was no significant difference in labelling between primary tumours and metastases for MIB1. Of the cytokeratins examined, CK 20 gave the strongest and most consistent reaction in both primary and secondary tumours. The results indicate that, for certain immunohistochemical markers, results are the same in both primary tumours and metastases. Hence, in these cases, antigens that are expressed on the primary tumour as well as on the metastases can serve as target molecules for immunologically based forms of treatment of metastases.

Animals↗
PubMed2004

[Genetic analysis and immunophenotyping in the diagnosis of hematological disease].

The developments in the fields of genetics and immunology and the application of these informations have significant consequences for the diagnosis of hematological diseases. The present article gives an introduction into the principles of several modern diagnostic techniques, which are applied in the diagnosis of hematological diseases. In addition, it summarizes the application of these techniques in the diagnosis of several acquired and inherited diseases. The most important method of immunophenotyping is FACS (fluorescence activated cell sorting) analysis, which is based on the automated recognition of fluorescently labelled monoclonal antibodies bound to specific antigens on the surface or in the cytoplasm of different cell populations of the immune system. Techniques from molecular biology and from cytogenetics are also relevant for the diagnosis of hematological diseases: they allow the identification of changes of the genetic material on the level of DNA (molecular biology) and chromosomes (cytogenetics). Molecular biological and cytogenetic methods coalesce in the field of molecular cytogenetics, which renders possible the identification of chromosome mutations, which are invisible by the classical cytogenetical approach, and difficult to detect by routine molecular biological analysis. Most hematological malignancies are associated with genomic changes, which can be identified by cytogenetic and/or molecular biological methods. These genetic changes usually correspond with a specific pattern of surface antigens of the tumour cells, which can be identified by FACS. The different mutations in different genes causing a large number of inherited hematological diseases can often be found by molecular analysis, too. For hematological neoplasias, the exact definition of the causative mutations is increasingly important for therapeutic decisions and follow-up analysis of minimal residual disease. For inherited diseases, the identification of mutations is often the basis for a correct genetic counselling of the family.

Chromosome Mapping↗
PubMed1999

Immunophenotypic characterization of human bone marrow endosteal cells.

In order to determine the relationship between bone marrow (bm) endosteal cells (EDC) and hemopoietic progenitors, we have analyzed the immunophenotype of EDC using various antibodies (Ab) against mesenchymal antigens. The Ab were applied on paraffin sections of normal bm (iliac crest, n=17; talus, n=1; phalanx, n=1), myeloregenerative bm (after chemotherapy), and hematologic disorders (acute myeloid leukemia (AML), n=8; chronic myeloid leukemia (CML), n=6; myelodysplastic syndromes (MDS), n=14; severe aplastic anemia (SAA), n=4; essential thrombocythemia (ET), n=2; idiopathic (primary) osteomyelo-fibrosis (IMF), n=1; polycythemia vera (PV), n=1). In normal bm, EDC were found to react with Ab against vimentin, tenascin, alpha-smooth muscle actin, osteocalcin, CD51, and CD56, but did not react with Ab against CD3, CD15, CD20, CD34, CD45, CD68, or CD117. An identical phenotype of EDC was found in AML, MDS, SAA, ET, IMF, PV, myeloregenerative bm, and peripheral bones lacking active hemopoiesis (talus, phalanx). In patients with CML, EDC reacted with Ab to CD51, but did not react with Ab to CD56. Based on their unique antigen profile, EDC were enriched from normal bm by enzyme digestion and cell sorting. However, these enriched cells (CD56+, CD45-, CD34-) did not give rise to hemopoietic cells under the culture conditions used, i.e. in the presence of the growth factors IGF-1, bFGF, SCF, IL-3, and GM-CSF Together, our data do not support the hypothesis that EDC are totipotent mesenchymal progenitors giving rise to hemopoietic cells.

Antigens, CD↗
PubMed2002

CD30 antigen expression in cutaneous inflammatory infiltrates of scabies: a dynamic immunophenotypic pattern that should be distinguished from lymphomatoid papulosis.

BACKGROUND: Expression of CD30 antigen is a distinct marker of lymphocyte activation that was originally described in the Reed-Sternberg cells of Hodgkin's disease. The observation of CD30+ cells has been considered a diagnostic feature of cutaneous CD30 lymphoid proliferations. However, CD30 expression has also been reported in some cutaneous benign inflammatory infiltrates. METHODS: Eleven skin biopsies from patients with scabies were double-blindly and retrospectively analysed. A panel of histopathological parameters and immunophenotypic expression of CD4, CD8, CD30 and S-100 antigens was studied. CD30 and S-100 antigens expression were related to clinical features. RESULTS: Large CD30+ cells were demonstrated in eight (8/11) biopsies, corresponding to patients with long-standing lesions (3 months or longer). However, no expression of the CD30 antigen was observed in all biopsy specimens (3/11) corresponding to early lesions (2 months or less). The presence of S-100 positive cells in the papillary dermis was an almost constant feature. CONCLUSIONS: CD30+ large cells seem to be a common feature in long-standing infiltrates of scabies. CD30 expression in scattered cells of a cutaneous lymphoid infiltrate cannot be assessed as a strong diagnostic argument of neoplastic cutaneous CD30+ lymphoid proliferation (lymphomatoid papulosis/cutaneous CD30+ lymphoma). Therefore, the possibility that large atypical CD30+ cells may be also present in several benign inflammatory diseases should be always considered.

Adult↗
PubMed1995

Immunophenotyping in presumed ocular histoplasmosis like retinopathy.

Four cases of presumed ocular histoplasmosis like retinopathy are presented. A detailed immunological assessment was carried out on the patients and a control group: lymphocyte immunophenotyping; flow cytometric analysis; HLA typing and T cell receptor variable region (TCR V region) expression were assessed. Analysis of TCR V region expression revealed no significant preferential expression. HLA typing also failed to reveal any links. All lymphocyte markers analysed were unremarkable, with the exception of CD38 which was significantly raised compared with controls (p < 0.01). This finding was confirmed by the use of two different CD38-specific monoclonal antibodies. The raised CD38 in our cases was shown to be persistent when the patients were retested after an interval of several months. Significantly, this may correlate with poor T cell function, as in Common Variable Immunodeficiency, making these patients more susceptible to various stimuli.

ADP-ribosyl Cyclase↗
PubMed2004

Correlation between karyotype and quantitative immunophenotype in acute myelogenous leukemia with t(8;21).

Acute myelogenous leukemia with t(8;21) is a distinct clinicopathologic entity in which the malignant myeloblasts display a characteristic pattern of surface antigen expression. Quantitative analysis of surface marker expression in patients with this chromosomal abnormality compared to acute myelogenous leukemia patients with a different karyotype has not been reported. From 305 consecutive newly diagnosed acute myelogenous leukemia patients underwent immunophenotyping and cytogenetic analysis at our center; 16 patients (5.2%) had a t(8;21). Fluorescence intensity values were obtained, using a set of reference microbeads, by conversion of mean channel fluorescence to molecular equivalent of soluble fluorochrome. Patients with t(8;21) displayed higher levels of CD34, HLA-DR and MPO expression (P < 0.001 for each) and lower levels of CD13 (P = 0.03) and CD33 (P = 0.02) expression. In order to study the sensitivity, specificity and predictive value of these markers, molecular equivalent of soluble fluorochrome thresholds were statistically determined. The statistically established threshold for each of the individual markers (CD34 > 60.5 x 10(3), HLA-DR > 176.1 x 10(3), MPO > 735.1 x 10(3), CD13 < 24.3 x 10(3) and CD33 < 17.3 x 10(3)) had a sensitivity of 100%, a specificity of 62-92% and a positive predictive value of 7-45%. In multivariate analysis, two quantitative patterns (CD34 > 60.5 x 10(3) and MPO > 176.1 x 10(3); CD33 < 17.3 x 10(3) and MPO > 176.1 x 10(3)) had a sensitivity, specificity and positive predictive value of 100%. These aberrant phenotypic patterns might help identify patients with t(8;21) at diagnosis and could be useful in minimal residual disease monitoring.

Antigens, CD↗
PubMed2000

Pagetoid reticulosis (Woringer-Kolopp disease): an immunophenotypic, molecular, and clinicopathologic study.

Pagetoid reticulosis (PR), also known as Woringer-Kolopp disease, is a form of cutaneous T-cell lymphoma that demonstrates striking epidermotropism on histologic examination. We present the histologic, immunologic, and molecular findings for seven patients who had PR. The patients ranged in age from 33 to 67 years. All patients presented with one or several thick plaques involving the distal extremities except for one patient, who presented with a tongue lesion. Immunohistochemical staining of the atypical lymphoid cells demonstrated a T-cell phenotype in all cases. In one of four frozen cases, the neoplastic cells were of T-helper cell phenotype (CD4 positive). Four of seven cases demonstrated a T-cytotoxic/suppressor cell phenotype (CD8 positive). The T-cell subset for the remaining two cases could not be determined. CD30 positivity and a high growth fraction as indicated by staining with Ki-67 were seen in three of seven and three of four cases, respectively. Genotypic analysis performed on three of our cases revealed T-cell receptor (gamma and/or beta) rearrangement, indicating a clonal proliferation. The clinical follow-up ranged from 15 months to 13 years. Four of seven patients are alive and free of disease after treatment with excision or local irradiation. One patient relapsed twice after treatment with radiation and photochemotherapy with 8-methoxypsoralen and UVA and was then lost to follow-up. The lesions of another patient resolved spontaneously but recurred at the same and in an additional site 5 years later. One patient recurred after electron beam therapy. The recurrent lesion improved with radiation therapy and local wound care but never resolved completely. The patient died of unrelated causes. Our findings suggest that PR is a distinct clinicopathologic entity, separate from unilesional mycosis fungoides, demonstrating a slow disease course. The disease is a clonal cutaneous T-cell lymphoma with relatively consistent clinical and histopathologic findings but a heterogeneous immunophenotypic profile.

Adult↗
PubMed2000

T-cell lymphoma presenting in the breast: a histologic, immunophenotypic and molecular genetic study of four cases.

Primary non-Hodgkin's lymphoma of the breast is uncommon. Most primary breast lymphomas are of B-cell phenotype, with only rare cases showing a T-cell phenotype. In this study, we report the clinicopathologic features of four cases of T-cell lymphoma in the breast. The patients all were female with a mean age of 48 years (range, 13 to 77 years). All cases showed immunoreactivity in paraffin-embedded tissue for T-cell markers CD3, CD45RO, and CD43. beta F1 was positive in three of four cases. The four cases were further subclassified as anaplastic large cell lymphoma (CD30 positive) of T-immunophenotype; natural killer/T-cell lymphoma; peripheral T-cell (CD4 positive), large cell type; and peripheral T-cell (CD8 positive, T-cell intracellular antigen positive), medium cell type. Three of the four cases were monoclonal for T-cell receptor beta and/or T-cell receptor gamma. The one case of natural killer/T-cell lymphoma was negative for monoclonality with both T-cell receptor beta and gamma by molecular diagnostic studies. In all cases, IgH was negative. Follow-up was obtained in three cases. Two patients died within less than 1 year after the diagnosis. The third patient died within 18 months of the diagnosis. Our results suggest an aggressive clinical course for T-cell lymphomas that present in the breast.

Adolescent↗
PubMed2000

Splenic angiosarcoma: a clinicopathologic and immunophenotypic study of 28 cases.

Primary angiosarcoma of the spleen is a rare neoplasm that has not been well characterized. We describe the clinical, morphologic, and immunophenotypic findings of 28 cases of primary splenic angiosarcoma, including one case that shares features of lymphangioma/lymphangiosarcoma. The patients included 16 men and 12 women, aged 29 to 85 years, with a mean of 59 years and median of 63 years. The majority of patients (75%) complained of abdominal pain, and 25% presented with splenic rupture. The most common physical finding was splenomegaly (71%). Seventeen of 21 patients were reported to have anemia. Macroscopic examination showed splenomegaly in 85% cases. Sectioning revealed discrete lesions in 88% of cases, ranging from well-circumscribed firm nodules to poorly delineated foci of necrosis and hemorrhage associated with cystic spaces. Microscopically, the tumors were heterogenous; however, all cases demonstrated at least a focal vasoformative component lined by atypical endothelial cells. Solid sarcomatous, papillary, and epithelioid growth patterns were observed. The solid sarcomatous component resembled fibrosarcoma in two cases and malignant fibroushistiocytoma in one case. Hemorrhage, necrosis, hemosiderin, extramedullary hematopoiesis, and intracytoplasmic hyaline globules were frequently identified. A panel of immunohistochemical studies revealed that the majority of tumors were immunoreactive for at least two markers of vascular differentiation (CD34, FVIIIRAg, VEGFR3, and CD31) and at least one marker of histiocytic differentiation (CD68 and/or lysozyme). Metastases developed in 100% of patients during the course of their disease. Twenty-six patients died of disease despite aggressive therapy, whereas only two patients are alive at last follow-up, one with disease at 8 years and the other without disease at 10 years. In conclusion, primary splenic angiosarcoma is an extremely aggressive neoplasm that is almost universally fatal. The majority of splenic angiosarcomas coexpress histiocytic and endothelial markers by immunohistochemical analysis, which suggest that some tumors may originate from splenic lining cells.

Adult↗
PubMed1998

Simultaneous detection of X and Y chromosomes by two-colour fluorescence in situ hybridization in combination with immunophenotyping of single cells to document chimaerism after sex-mismatched bone marrow transplantation.

A powerful approach to documenting engraftment after allogeneic BMT is the quantification of the degree of chimaerism in distinct haematopoietic cell lineages. This cannot be achieved by the recently developed, quantitative, modifications of PCR amplification of highly polymorphic DNA markers, unless this technique is applied to separated cell populations. Here, we report the development of a new method, in which cells are simultaneously characterized by enzymatic immunophenotyping and identified for their origin by two-colour fluorescence in situ hybridization with X and Y chromosome-specific DNA probes (XY-FISH/immunostaining). The method enables the rapid, reliable and quantitative analysis of chimaerism within distinct cell lineages after sex-mismatched BMT, without the requirement for cell separation techniques. This is illustrated by investigation of the pattern of chimaerism in patients receiving a sex-mismatched BMT for the treatment of primary immunodeficiencies. The results obtained with the quantitative XY-FISH/immuno staining method show a good correlation with the data generated by the semi-quantitative analysis of PCR amplified minisatellites in FACS-sorted cell fractions. In addition, XY-FISH/immunostaining was successfully applied to detect materno-fetal engraftment of T cells in a SCID patient.

Bone Marrow Transplantation↗
PubMed1997

Flow cytometry CD45 gating for immunophenotyping of acute myeloid leukemia.

A flow cytometry method has been introduced into the routine investigation of whole bone marrow samples following red blood cell lysis on the basis of a primary CD45/side scatter (SSC) gating procedure. Blast cells were first identified by CD45/SSC gating in 74 cases of acute myeloid leukemia (AML) and the results were compared to a conventional FSC/SSC gating procedure and to MGG-staining smears. The percentages of blast cells in these samples as defined by the morphological analysis of MGG smears correlated better with the values determined by CD45/SSC gating (r = 0.94) than with the blast cell counts recorded with FSC/SSC gating (r = 0.76). These findings were not surprising because while CD45 expression was regularly lower on leukemic blasts than on normal lymphoid and monocytic cells, the FCS/SSC characteristics of these populations were overlapping. In 53 samples, the blast cell populations were also analyzed with a panel of FITC-conjugated monoclonal antibodies that were utilized in double labeling with CD45-PE. We show that the CD45/SSC gating procedure improved phenotypic determination of the blast cells in three ways: (1) by discriminating between leukemic blast cells and residual normal cells; (2) by excluding normal cells from the phenotypic analysis of leukemic blast cells; and (3) by identifying blast cell heterogeneity in many cases of leukemia on the basis of different CD45 display. Moreover, this immunophenotyping procedure on whole bone marrow samples also allowed an efficient discrimination between the various cell lineages and facilitated the analysis of leukemic blasts present in low proportions.

Acute Disease↗
PubMed1998

Induction of clinical remission in T-large granular lymphocyte leukemia with cyclosporin A, monitored by use of immunophenotyping with Vbeta antibodies.

A 54-year-old woman presented with a severe autoimmune anemia, thrombocytopenia, neutropenia (Evans' syndrome), and CD8+ lymphocytosis, without signs of lymphadenopathy or splenomegaly. A diagnosis of T cell large granular lymphocyte (T-LGL) leukemia was made, based on cytomorphology, the typical CD3+/CD4-/CD8+/CD16+/CD56-/CD57-/HLA-DR(+/-) immunophenotype of the lymphocytosis (9 x 10(9)/l), and biallelic clonally rearranged T cell receptor beta (TCR beta) genes. Clonality of the TCR alphabeta+ T-LGL was also demonstrated with a panel of antibodies against variable domains of TCR beta chains, which showed single Vbeta7.1 expression on the CD3+ T-lymphocytes. After treatment failure with corticosteroids, splenectomy, and cyclophosphamide, respectively, a complete clinical remission was induced and sustained with cyclosporin A. Vbeta7.1/CD8/CD3 triple immunofluorescence stainings appeared to be valuable for titrating the cyclosporin A dosage by monitoring the T-LGL cells during treatment.

Anemia, Refractory↗
PubMed1998

Acute myeloid leukemia with 11q23 translocations: myelomonocytic immunophenotype by multiparameter flow cytometry.

11q23 translocations (t(11q23)) are recurring cytogenetic abnormalities in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia, involving the same gene, ALL1 (or MLL). Mixed lineage antigen expression has been reported in these leukemias, but its frequency and clinical significance are unknown. We immunophenotyped leukemia cells from 19 adult de novo AML patients with t(11q23) by multiparameter flow cytometry. Translocations included t(6;11)(q27;q23), t(9;11)(p22;q23), t(9;11;19)(p22;q23;q13.3), t(2;11)(11;17)(q37;q11q23;q11), t(11;17)(q23;q25), t(11;19)(q23;p13.1), t(11;19)(q23;p13.3) and t(11;22)(q23;q11). FAB types were M4 and M5. The committed stem cell and myeloid antigens HLADr, CD4dim, CD11b, CD13, CD15, CD32, CD33, CD38 and CD64 were each expressed in 80-100% of cases, and the early stem cell and lymphoid antigens CD34, CD56, CD3, CD2 and CD7 in 42, 39, 16, 5 and 5%, respectively. Antigen expression frequencies did not differ from those in 443 adequately karyotyped M4 and M5 cases without t(11q23). Fifteen patients (79%) attained complete remission (CR); median CR duration and survival were 10.0 and 15.1 months. CR duration and survival did not correlate with antigen expression. In particular, patients with t(9;11) survived longer than those with other t(11q23) (median not reached vs 7.6 months; P = 0.048), but antigen expression did not differ in the two groups. Thus frequencies of lymphoid antigen expression are similar in AML with t(11q23) and in other FAB M4 and M5 cases, treatment outcome does not differ in t(11q23) cases with and without lymphoid antigen expression, and better outcome of patients with t(9;11) compared to other t(11q23) does not correlate with differences in antigen expression. Mixed lineage antigen expression is not a distinctive feature of AML with t(11q23).

Adolescent↗
PubMed1998

Hematologic malignancies with t(4;11)(q21;q23)--a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants.

A total of 183 hematologic malignancies with t(4;11)(q21;q23), including five variant translocations, were collected by the Workshop. Clinical, morphologic and immunophenotypic features were compiled, and karyotypes with variant t(4;11) or secondary chromosomal aberrations were reviewed. All cases were acute leukemias (AL): 173 acute lymphoblastic leukemias (ALL), six acute myeloid leukemias (AML), three unclassifiable AL, and one biphenotypic AL. Ten patients had treatment-associated AL. Females were overrepresented (104 vs 79) and the age distribution was clearly nonrandom; 34% of the cases occurred in infants below the age of 12 months. The remaining AL were evenly distributed among the other age groups, with the oldest patient being 79 years old. An increased white blood cell count (WBC) was reported in more than 90% of the cases, with hyperleukocytosis (> or =100 x 10(9)/l) in 64%. Additional chromosomal changes were detected in 55 (30%) cases, most often gain of the X chromosome, i(7)(q10), and trisomy 8, with frequent breakpoints in 1p36, 1q21, 7q10, 11p15, 12p13, 17p11, and 17p10. All recurrent secondary changes resulted in genomic imbalances, in particular gains of 1q, 7q, 8, and X and losses of 7p and 17p. Event-free and overall survival (EFS and OS) could be ascertained in 170 and 171 patients, respectively. Kaplan-Meier estimates of EFS and OS showed no differences with regard to gender, WBC, or presence of secondary chromosomal abnormalities, and there was no increase of EFS or OS among the 55 cases that had undergone bone marrow transplantation. However, age had an important prognostic impact, with significantly (P < 0.0001) longer EFS and OS in children 2-9 years old than among infants and younger children, patients aged between 10 and 39 years and older adults.

Acute Disease↗
PubMed1998

Relation between age, immunophenotype and in vitro drug resistance in 395 children with acute lymphoblastic leukemia--implications for treatment of infants.

The prognosis of infant ALL, characterized by a high incidence of the immature CD10 negative B-lineage ALL (proB ALL) is poor. This study aimed to determine the resistance profile of infant ALL cells. In vitro drug resistance was determined by the MTT assay of 395 children with ALL at initial diagnosis: there were 21 infants <1.5 years of which nine <1 year, 284 children aged 1.5-10 years (intermediate age group) and 90 children >10 years. Immunophenotyping resulted in 310 cALL/preB ALL, 69 T-ALL, 15 proB ALL and one unknown cases. The following drugs were tested: daunorubicin, doxorubicin, mitoxantrone, idarubicin (Ida), prednisolone (Pred), dexamethasone (DXM), vincristine (VCR), Asparaginase (Asp), 6-MP, 6-TG, AraC, VM26 and 4-HOO-ifosfamide (Ifos). Infants <1.5 years were significantly more resistant to Pred (>500-fold), Asp (11-fold) and VM26 (2.7-fold) but significantly more sensitive to Ara-C (2.3-fold) compared to the intermediate age group. When analyzing infants <1 year of age similar results were found. ProB ALL cells (seven infants <1.5 years; eight children >1.5 years) were significantly more resistant to glucocorticoids, Asp, thiopurines, anthracyclines and Ifos compared to cALL/preB ALL but more sensitive to Ara-C. Cells from children >10 years were significantly more resistant to Pred, DXM, Asp, Ida and 6-MP. T-ALL cells showed a strong resistance to Pred, Asp and VCR and a mild but significant resistance to all other drugs except thiopurines and VM26. We conclude that the poor prognosis of infant ALL is associated with a resistance to glucocorticoids and Asp. However, ALL cells from infants show a relatively high sensitivity to Ara-C which suggests that infants with ALL might benefit from treatment schedules that incorporate more Ara-C than the current treatment protocols.

Adolescent↗