Long-term follow-up of a well-differentiated mesothelioma of the peritoneum in a 2-year-old girl.
Explore the source record for details and available documents.
Diagnosis, Differential↗
Biomedical subjects
A Reiter
Publications and source records attributed to A Reiter.
Molecular monitoring of residual disease in chronic myelogenous leukemia patients after therapy.
The degree of tumor load reduction after therapy, which is determined by the degrees of cytoreduction and cytogenetic response, is an important prognostic factor for patients with chronic myelogenous leukemia (CML). Conventional metaphase analysis is considered to be the "gold standard" for evaluating cytogenetic response. The frequency of cytogenetic analysis can be reduced considerably if patients are monitored by molecular methods, such as quantitative Southern blot, fluorescence in situ hybridization (FISH), quantitative western blot, or competitive reverse transcriptase polymerase chain reaction (RT-PCR). Molecular methods can be performed on peripheral blood specimens and are therefore less invasive than cytogenetic analyses of bone marrow metaphases. Furthermore these techniques are applicable to Ph-negative/BCR-AbL-positive cases. Results obtained by Southern blotting, western blotting, and FISH are readily quantifiable but their sensitivity is not generally superior to that of cytogenetic methods. RT-PCR is by far the most sensitive method. Quantitative RT-PCR analysis is the method of choice for monitoring patients after bone marrow transplantation (BMT). Using competitive PCR in patients after BMT, reappearance and/or rising levels of BCR-ABL transcripts can be detected prior to relapse. All complete cytogenetic responders to interferon-alpha are positive for BCR-ABL transcripts. The level of residual disease spans a range over found orders of magnitude. In both interferon-alpha-treated patients and patients after BMT a good correlation between BCR-ABL transcript numbers per microgram of RNA and cytogenetic results has been found. Variables in the competitive PCR assay may be controlled for by quantification of transcripts of the normal ABL gene as an internal standard. We suggest a stepwise strategy for diagnosis and follow-up of CML patients employing molecular methods.
Blotting, Southern↗
Periprosthetic mineralization around cementless total hip endoprosthesis: longitudinal study and cross-sectional study on titanium threaded acetabular cup and cementless Spotorno stem with DEXA.
In a prospective longitudinal study over 2 years and a separate cross-sectional study more than 5 years after operation, we analyzed periprosthetic bone mineral density (BMD) after cementless total hip arthroplasty (THA) (press-fit cementless Spotorno stem, Mecron threaded acetabular cup) by dual-energy X-ray absorptiometry (DEXA). BMD was analyzed in a longitudinal prospective study (n = 53 patients: 29 women, 24 men) and in a separate cross-sectional study (n = 23 patients: 13 women, 10 men) with good clinical outcome (Merle d' Aubigne score > 12). Regions of interest were defined according to Gruen (ROI 1-7) and as netto average ROI (NETAVG I) for the periprosthetic femur, and according to De Lee and Charnley (ROI I-III) and as NETAVG II for the periprosthetic acetabulum. BMD during follow-up was compared with immediate postoperative values of the affected limb. Mean precision error (CV%) was 2.6 +/- 0.5% for ROI 1-7 and 1.3 +/- 0.9% for ROI I-III. BMD significantly decreased in the periprosthetic femur and acetabulum during the first 3 months after operation. At the femur, BMD (NETAVG I) for women and men, respectively, was 92.4% and 87.5% at 6 months, then 89.4% and 96.2% at 2 years. ROIs around the proximal stem showed the lowest absolute values and decreased most during follow-up (to 79.9% ROI 1 and 68.2% ROI 7, respectively). Mineralization around the cup (NETAVG II), respectively, amounted to 81.1%, 82.6% at 6 months, then 80.1% and 93.8% at 2 years. The medially placed ROI II demineralized most (respectively, 72.1% and 76.7%). More than 5 years after THA, BMD in the femur showed little change, but decreased significantly to 76.4% and 79.1%, respectively, around the cup (NETAVG II). DEXA is a useful method for analyzing changes of mineralization around cup and stem of cementless THA. The results reflect the different stress on the periprosthetic bone after implantation of THA in defined ROIs, supporting earlier reported good clinical results of the Spotorno stem and increased loosening rate of threaded acetabular cups after 5 years.
Absorptiometry, Photon↗
XIX Symposium of the International Association for Comparative Research on Leukemia and Related Diseases, July 13-18 Mannheim/Heidelberg, Germany, 1997.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Down's syndrome in childhood acute lymphoblastic leukemia: clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Münster Group.
Clinical characteristics, treatment response and outcome were evaluated in children with Down's syndrome (DS) and acute lymphoblastic leukemia (ALL) as compared to other children with ALL (NDS). Sixty-one DS and 4049 NDS patients, receiving intensive antileukemic treatment during four consecutive trials (ALL-BFM 81, 83, 86 and 90) of the Berlin-Frankfurt-Münster Group (BFM), were retrospectively analyzed. DS and NDS children did not differ with respect to sex, leukocyte count, CNS leukemia and cytogenetic translocations. The DS cohort was slightly older (P=0.04), presented predominantly with the common while lacking the T immunophenotype (P=0.005), had a lower frequency of hyperdiploidy (P=0.004) and tended to have a better initial steroid response (P=0.057). Therapy-associated morbidity especially during high-dose methotrexate and a subsequent need for treatment modification occurred in 43% of all DS patients. Event-free survival (EFS) was slightly worse in children with DS (58+/-8% vs 70+/-1%, P=0.14), mainly due to rather late bone marrow recurrences. However, EFS in DS patients was comparable to the NDS group once they either received treatment with no major modifications (65+9% vs 70+/-1%, P=0.66) or were <6 years of age, irrespectively of therapy modifications (73+/-9% vs 74+/-1%, P=0.7). Cox regression analysis revealed that DS was an adverse prognostic factor for patients having completed therapy (P=0.0107), but was not prognostic at diagnosis (P=0.103). Age > or = 6 years, suboptimal treatment and infectious problems contributed to the slight inferior EFS in children with ALL and Down's syndrome. Therefore, most of these patients can be successfully treated if receiving intensive antileukemic treatment with no major modifications, but they require more sophisticated management of toxicity.
Antineoplastic Combined Chemotherapy Protocols↗
Expression and regulation of c-kit receptor and response to stem cell factor in childhood malignant T-lymphoblastic cells.
The cytokine stem cell factor (SCF) synergizes with IL-7 to enhance the proliferation of thymocytes. We therefore investigated the role of the SCF receptor, the protooncogene c-kit, in the pathogenesis of pediatric T-lineage malignancies. Expression and regulation of c-kit in cells from children with non-Hodgkin's lymphoma (T-NHL) or acute lymphoblastic leukemia (T-ALL) and the proliferative effect of SCF on these cells were examined in seven cell lines and 21 biopsy tumor cell preparations. Inducibility of c-kit receptors by SCF, IL-1beta, IL-2, IL-7, TGF-beta, TNF-alpha, PMA or calcium ionophore A23187 was studied by flow cytometry (FCM). C-kit receptors were detected in three out of seven T-lymphoblastic cell lines and in nine out of 21 biopsy tumor cell preparations. Upregulation of c-kit could be induced by cultivation, and to a higher extent by cultivation and addition of IL-1beta, TNF-alpha, TGF-beta or A23187. Downregulation of c-kit occurred in the presence of SCF or PMA. SCF caused a downregulation of c-kit receptors in eight of nine, and a proliferative response in three of 11 c-kit-positive T-lymphoblastic cell preparations. We conclude that c-kit is able to transduce a growth stimulatory signal in some T-lymphoblastic cells and that its expression may not be detectable in a resting metabolic or proliferative state.
Antigens, CD34↗
Should a platelet limit of 600 x 10(9)/l be used as a diagnostic criterion in essential thrombocythaemia? An analysis of the natural course including early stages.
In order to evaluate the natural history of essential thrombocythaemia (ET), clinical data and prognostic factors of 143 patients with ET were retrospectively analysed (mean observation time 6.1 +/- 4.6 years). In 42 patients the early phase of the disease with initial platelet counts between 250 and 600 x 10(9)/l was assessed. In most early cases, ET was suggested by clinical symptoms (79%) and increased megakaryopoiesis (95%) with abnormal megakaryocytes in bone marrow histology (n = 34) and cytology (n = 5). Other myeloproliferative disorders and reactive thrombocytosis were excluded according to the diagnostic criteria of the Polycythemia Vera Study Group. During follow-up of the 38 early cases not treated cytoreductively at diagnosis, the platelet counts increased to >600 x 10(9)/l in 28 patients (74%) and remained between 450 and 600 x 10(9)/l in 10 patients (26%). In primarily asymptomatic patients (n = 46) with initial platelet counts above (n = 37) and below 600 x 10(9)/l (n = 9) the rates of increase of symptomatic patients were similar at about 7% per year. No influence of the initial platelet count on survival was seen in multivariate analysis of prognostic factors which included all 143 cases. Survival was mainly influenced by the rate of ET-related complications during follow-up (P = 0.002). Analysing the influence of cytoreductive therapy on symptom-free survival, platelet reduction benefited patients under 60 years (19 cytoreductively treated v 65 untreated patients, P = 0.075). The results demonstrate the possible clinical relevance of the early stages of ET and suggest that the features of pathologic megakaryopoiesis in the bone marrow are a more reliable diagnostic criterion than a definite platelet limit. Therefore, further therapeutic studies should include all stages of the disease and all age groups.
Adult↗
BCR-ABL-positive progenitors in chronic myeloid leukaemia patients in complete cytogenetic remission after treatment with interferon-alpha.
To determine the source of residual disease detected in patients with chronic myeloid leukaemia (CML) in complete cytogenetic remission (n=8) after treatment with interferon-alpha (IFN-alpha), we have tested CFU-GM colonies grown from bone marrow mononuclear cells or from plastic-adherent (Pdelta) cells for BCR-ABL mRNA using a nested multiplex RT-PCR. We compared our results with those obtained by analysis of colonies from newly diagnosed patients (n=4) and patients achieving no cytogenetic response (n=1) or incomplete cytogenetic response to treatment with IFN-alpha (n=5). A total of 1239 informative colonies were analysed. A small proportion of BCR-ABL-positive colonies was detected in all eight patients in complete cytogenetic remission, suggesting the persistence of leukaemia that could potentially lead to relapse. The overall proportion of BCR-ABL-positive colonies in patients achieving a cytogenetic response to IFN-alpha correlated with the levels of BCR-ABL transcripts detected in the peripheral blood by competitive RT-PCR (P=0.004). We conclude that residual disease detected in the peripheral blood of complete cytogenetic responders to IFN-alpha is at least partly derived from clonogenic myeloid cells. It is probable that the leukaemia clone in CML is only very rarely or never entirely eradicated by treatment with IFN-alpha.
Adult↗
Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement.
Two distinct leukemia syndromes are associated with abnormalities of chromosome band 8p11. First, a myeloproliferative disorder with features characteristic of both chronic myeloid leukemia and non-Hodgkin's lymphoma and second, an acute myeloid leukemia (AML) with French-American-British (FAB) M4/5 morphology and prominent erythrophagocytosis. The two syndromes are exemplified by a t(8;13)(p11;q12) and a t(8;16)(p11;p13), respectively, but cytogenetic variants of both have been described. Recently, the t(8;16) has been cloned and shown to fuse the MOZ gene at 8p11 to the CBP gene at 16p13. We have used fluorescence in situ hybridization (FISH), Southern blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) to refine the 8p11 breakpoint in three cases with t(8;13)(p11;q12) and in a single case of AML-M5 with a clinical picture apparently identical to that found in patients with a t(8;16), but characterized by an inv(8)(p11q13). FISH analysis was performed with several 8p11 CEPH yeast artificial chromosome (YAC) clones. YAC 782H11 was centromeric to the one case with t(8;13) tested, but was telomeric to the inv(8). YAC 847B12 was telomeric to both the t(8;13) and the inv(8), whereas YAC 829D12 was centromeric to the t(8;13), but split by the inv(8). Southern blotting and PCR of YAC 829D12 showed that it contained the MOZ gene. A 900-bp MOZ fragment encompassing the published t(8;16) breakpoint was amplified by PCR from normal peripheral blood leukocyte cDNA and used to probe Southern blots of patient DNA. A rearrangement was detected in the case with inv(8), but not in any of the three cases with t(8;13). Southern blotting with a CBP probe and RT-PCR with MOZ and CBP primers suggested that the inv(8) does not result in a cryptic MOZ-CBP fusion. It is likely, therefore, that MOZ is fused to a novel gene at 8q13 in this case. We conclude that the t(8;13) breakpoint is flanked by YACs 782H11 and 847B12 and is at least 1 Mb telomeric to MOZ. MOZ is involved, however, in a new variant of the t(8;16).
Acetyltransferases↗
Quantitative assessment of callus distraction using dual energy X-ray absorptiometry.
Bone mineralisation during and after limb lengthening procedures on the femur or tibia using unilateral fixators has been monitored quantitatively using dual energy X-ray absorptiometry (DEXA). We measured the bone mineral density (BMD) prospectively in the newly formed callus, in the bone adjacent to the callus and in the proximal femur. In twenty-one patients we showed a typical course with a peak value at 4-6 weeks after beginning distraction and a minimum value at maximum distraction. In the consolidation period the BMD in the distraction gap increased until the fixator was removed. The BMD in the regenerated bone increased faster in the regions of interest (ROI) opposite the fixator compared to those near it. Dynamisation caused more homogeneous regeneration equalising VBMD in the different ROIs. The BMD in the proximal femur of the leg which was operated on decreased to 67% and in the opposite leg to 87% of the preoperative value. DEXA provides a precise and quantitative assessment of callus and bone mineralisation during limb lengthening and helps in understanding what is happening during these procedures.
Absorptiometry, Photon↗
High incidence of significant bone loss in patients with severe congenital neutropenia (Kostmann's syndrome).
OBJECTIVE: Clinical observation of bone pain, unusual fractures in two patients, and diffuse osteopenia/osteoporosis led us to assess bone mineral content and density in 30 patients with severe congenital neutropenia who were treated with recombinant-methionyl-human granulocyte colony-stimulating factor (r-metHuG-CSF). STUDY DESIGN: We reviewed roentgenograms in 29 of these 30 patients to evaluate bone loss before and during treatment. In addition, in 17 of the 30 patients, bone mineral status could be assessed by both quantitative computed tomography (Q-CT; n = 16) and dual energy x-ray absorptiometry (DXA; n = 1). In one patient, Q-CT was not possible because of severe vertebral fractures. RESULTS: Of the 30 patients investigated, 15 had evidence of osteopenia/osteoporosis observed on spine radiographs (n = 5), on Q-CT/DXA (n = 1/n = 1), or on radiographs and Q-CT (n = 8). In 13 of the 30 patients, only a lateral radiograph of the lumbar spine was available, 5 of 13 showing either increased kyphosis and wedging of the vertebrae or compression fractures of the vertebral bodies, indicating severe established osteoporosis. In eight patients, the findings of the spinal radiographs were normal. In nine patients, spinal radiographs were taken before r-metHuG-CSF treatment. Osteoporotic vertebral deformation (n = 3) or reduced bone mass (n = 3) was seen in six of these nine patients. The levels of serum biochemical markers of bone metabolism were all within normal ranges except for mild elevation of the serum alkaline phosphatase level. The degree of spinal bone mineral loss did not correlate with dose and duration of r-metHuG-CSF treatment or with the age or sex of the patients. CONCLUSIONS: These data indicate a high incidence of bone mineral loss in children with severe congenital neutropenia. The underlying pathogenesis of bone demineralization is not clear. It is more likely that the bone loss was caused by the pathophysiologic features of the underlying disease, but it is possible that r-metHuG-CSF accelerates bone mineral loss.
Adolescent↗
TEL is one of the targets for deletion on 12p in many cases of childhood B-lineage acute lymphoblastic leukemia.
Abnormalities of the short arm of chromosome 12 including loss of heterozygosity (LOH) and TEL/AML-1 fusion resulting from a t(12;21)(p13;q22) translocation are frequently observed in childhood acute lymphoblastic leukemia (ALL). We investigated 21 DNA samples of childhood ALL which had LOH at 12p13. Rearrangement of TEL was observed in eight cases and another case showed a homozygous deletion of TEL. Two informative samples with TEL rearrangement had a deletion localized to the 5' region of this gene. The deletion in these two cases includes the helix-loop-helix (HLH) domain. This is consistent with the hypothesis that the normal tel can heterodimerize with the TEL/AML-1 gene product and inhibit the transforming capacity of the chimeric protein. Presumably, loss of the HLH of the normal remaining TEL allele abrogates this tumor suppressor-like function. The case with homozygous deletion of TEL is also consistent with this gene having qualities of a tumor suppressor. One unusual case had T-ALL rather than B-lineage ALL and the leukemic cells had rearrangement of TEL, but they did not have an alteration of the remaining TEL allele suggesting that the etiology of this disease may be different. This analysis further emphasizes the importance of loss of the normal TEL allele in childhood precursor B-lineage ALL.
Blotting, Southern↗
BCR/ABL-negative progenitors are enriched in the adherent fraction of CD34+ cells circulating in the blood of chronic phase chronic myeloid leukemia patients.
Philadelphia chromosome-positive (Ph+) hemopoietic cells predominate in patients with chronic myeloid leukemia (CML) in chronic phase, but some Ph presumably normal stem cells persist in most patients. Ph cells are relatively frequent, compared to mature cell populations, in primitive hemopoietic cell populations from CML patients. We have purified CD34+ cells from chronic phase CML blood and separated them into two fractions on the basis of adherence or non-adherence to tissue culture plastic. We also separated CD34+ CML cell populations into HLA-DR(hi) and HLA-DR(lo) fractions and CD38(hi) and CD38(lo) fractions by flow cytometry. The CD34+ cells that adhered to plastic were predominantly CD33-, CD38- and HLA(-)-DR; cells with these phenotypic properties were significantly rarer in the CD34+ non-adherent cell population (P = 0.008-0.02). Expression of p210 BCR/ABL mRNA by adherent, non-adherent, HLA-DR(hi) and HLA-DR(lo)CD34+ cell subpopulations was demonstrated by RT-PCR. Using fluorescence in situ hybridization (FISH) in conjunction with BCR and ABL probes we detected Ph+ and Ph- cells in both adherent and non-adherent CD34+ cell fractions of 15/15 patients studied and in the HLA-DR(lo) or CD38(lo) sorted CD34+ cell fractions. The concentration of Ph- cells in the adherent CD34+ cell fraction was three-fold higher than in the non-adherent fraction (P = 0.001). Ph- adherent cells were detected in untreated CML patients and as late as 6 years after diagnosis of CML in patients treated with hydroxyurea (HU) or interferon-alpha (IFN-alpha). We conclude that whilst appreciable numbers of Ph- primitive hemopoietic progenitors are present in the circulation in untreated patients and also in treated patients in late chronic phase, the majority of cells expressing CD34 but not CD33, CD38 or HLA-DR antigens, are part of the CML clone.
Adult↗
Comparative analysis of the impact of risk profile and of drug therapy on survival in CML using Sokal's index and a new score. German chronic myeloid leukaemia (CML)-Study Group.
Survival times in chronic myeloid leukaemia (CML) may vary widely depending on the risk profiles of patients. This fact is frequently not, or not sufficiently, considered in evaluating survival in CML, and some studies do not report risk profiles. Therefore we analysed the relative impact of risk profile and therapy on survival using the median survival times of therapy groups and of risk groups of the three-arm randomized German CML Study I (interferon alpha v hydroxyurea v busulphan; median survival times 65 v 56 v 45 months, n = 490, median observation time 70.4 months). The impact of risk profile (Sokal) on survival as determined by the survival difference between high and low risk patients (40 months) was twice the maximum survival difference between treatment groups (20 months). A similar ratio was obtained after stratification for therapy and for risk profile. Since Sokal's index has been reported to prognostically discriminate IFN-treated patients less well than chemotherapy-treated patients, a new score with better discrimination of IFN-treated patients was also used. The results were similar for both scores. We conclude that the risk profile at diagnosis is still more important for survival of CML patients than therapy. Therefore patients should be stratified according to risk profile for comparisons of survival times between studies and treatment arms.
Adolescent↗
Absence of IL-6 receptor expression in fresh childhood Burkitt's lymphoma cells and induction of IL-6 receptors by Epstein-Barr virus in vitro.
Interleukin-6 (IL-6) is a cytokine which is necessary for the differentiation of activated B cells and growth of early haemopoietic progenitors. It is used for ex-vivo expansion of myeloid progenitors in the setting of high-dose chemotherapy with autologous bone marrow transplantation (BMT). Expression of the IL-6 receptor (IL-6R) was examined in six fresh Burkitt's lymphoma (BL) cell preparations and 12 BL cell lines by reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry (FCM). Inducibility of IL-6R mRNA expression by Epstein-Barr virus (EBV) was studied by comparing two uninfected cell lines with the same cell lines infected by EBV The phenotype of the BL cells lines was analysed by FCM and by proliferation assays in the presence of anti-IgM antibodies. None of the fresh BL cells expressed the IL-6 receptor. The BL cell lines expressed varying degrees of IL-6R mRNA and protein. In vitro infection of EBV-negative BL cell lines resulted in up-regulation of IL-6R mRNA. There was no proliferative response of the BL cell lines to IL-6, including the cells that expressed the receptor. Compared to uninfected BL cell lines, EBV-infected cell lines and lymphoblastoid cell lines (LCLs) showed a weaker or no response to anti-IgM antibodies, indicating a more mature phenotype of these cells. We conclude that the IL-6 receptor is not expressed in fresh childhood BLs, but only in BL cell lines. EBV infection in vitro leads to an up-regulation of IL-6R mRNA but not to increased proliferation. This makes growth stimulation of contaminating BL cells in the setting of autologous BMT unlikely.
Antigens, CD↗
Molecular response of CML patients treated with interferon-alpha monitored by quantitative Southern blot analysis. German chronic myeloid leukaemia (CML) Study Group.
We analysed 459 samples from 206 chronic myeloid leukaemia (CML) patients at diagnosis and during or after treatment with interferon-alpha (IFN-alpha) by quantitative Southern blot analysis for BCR rearrangement. In a minority (2%) of Ph-positive patients, no BCR rearrangement was detectable due to breakpoints outside the major breakpoint cluster region (M-bcr) or possibly due to M-bcr deletions. Results from 235 samples were compared with the proportion of Ph-positive metaphases found in contemporaneous bone marrow specimens analysed by conventional cytogenetics. The rank correlation between both methods was 0.82 (P < 0.001). The proportion of CML cells in samples determined by Southern blot analysis (BCR ratio) was significantly different between cytogenetically-defined minor, partial, and complete response groups (P < 0.001). Empirically-derived cut-off points in the BCR ratio were introduced in order to define molecular response groups for comparison to standard cytogenetic response groups: a BCR ratio of 0% was defined as complete molecular response and ratios of 1-24%, 25-50%, and > 50% were defined as partial, minor, and no molecular response, respectively. Using these cut-off points the concordance between both methods was 67% (P < 0.0001), a major cytogenetic response could be predicted or excluded in more than 90% of cases (P < 0.0001). Our findings demonstrated that quantitative Southern blot was as sensitive as cytogenetics and as peripheral blood samples are suitable for this technique it should be considered as the method of choice for routine monitoring IFN-alpha therapy in CML patients.
Adolescent↗
The rate and kinetics of molecular response to donor leucocyte transfusions in chronic myeloid leukaemia patients treated for relapse after allogeneic bone marrow transplantation.
We have assessed the molecular response of 30 consecutive patients with chronic myeloid leukaemia (CML) treated for relapse after allogeneic bone marrow transplantation (BMT) by donor leucocyte transfusions (DLT). Response was evaluated by qualitative nested and quantitative competitive RT-PCR for BCR-ABL mRNA at various time intervals before and after DLT. The probability of attaining molecular remission at 2 years was 61% (95% CI 42-78%). Disease state at the time of DLT was significantly associated with response: molecular remission was achieved for 9/10 (90%) patients treated early (cytogenetic or molecular relapse) compared to only 8/20 (40%) patients treated late (haematological relapse; P = 0.009). The Kaplan-Meier estimates of molecular remission at 2 years post DLT for patients treated in early or late relapse were 86.6% and 47.3% respectively (P = 0.004). The median time interval from DLT to molecular remission was 11.0 months (range 2.5-32). Molecular remissions were durable for most (15/17) patients (median follow-up 21.2 months; range 0-55). Two patterns of molecular response were found: a very rapid decline after an initial lag phase or a more gradual decline over a period of several months. We conclude that molecular monitoring is a sensitive indicator of response to DLT; different kinetics of molecular response may reflect disease heterogeneity or differences in the mode of action of DLT.
Bone Marrow Transplantation↗
Role of cranial radiotherapy for childhood T-cell acute lymphoblastic leukemia with high WBC count and good response to prednisone. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster groups.
PURPOSE: The ALL-BFM 90 and AIEOP-ALL 91 studies share the same treatment backbone and have 5-year event-free survival (EFS) rates close to 75%. This study evaluated the impact of differing presymptomatic CNS therapies in T-cell acute lymphoblastic leukemia (T-ALL) patients with a good response to prednisone (PGR) according to WBC count and Berlin-Frankfurt-Münster (BFM) risk factor (RF). PATIENTS: A total of 192 patients (141 boys; median age, 7.5 years) with T-ALL, PGR, RF less than 1.7, and no CNS leukemia diagnosed between 1990 and 1995 were enrolled onto the ALL-BFM 90 (n = 123) or AIEOP-ALL 91 (n = 69) study. Presymptomatic CNS therapy consisted of cranial radiation (CRT) and intrathecal methotrexate (I.T. MTX) (11 doses) in the BFM study and of extended triple intrathecal therapy (T.I.T.) (17 doses) in the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) study. Patients were divided into a low-WBC group (WBC count < 100,000/microL) and a high-WBC group (WBC count > 100,000/microL). EFS was compared using the log-rank test. RESULTS: For patients treated with CRT and I.T. MTX (BFM group), the 3-year EFS rate was 89.8% (SE = 3.5) for 99 patients in the low-WBC group versus 81.9% (SE = 8.2) in the high-WBC group (difference not significant). Conversely, for patients treated with T.I.T. alone (AIEOP group), the EFS rate was 80.6% (SE = 5.6) in 55 patients with a low WBC count versus 17.9% (SE = 11.0) in 14 patients with a high WBC count (P < .001). CONCLUSION: These data suggest that CRT may not be necessary in PGR T-ALL patients with a WBC count less than 100,000/microL; on the contrary, in patients with a high count, extended T.I.T. may be inferior to CRT and I.T. MTX.
Adolescent↗