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E Mahlamäki

Publications and source records attributed to E Mahlamäki.

At least 19 recordsLinked to original sources
PubMed2006

High-dose melphalan (200 mg/m2) supported by autologous stem cell transplantation is safe and effective in elderly (>or=65 years) myeloma patients: comparison with younger patients treated on the same protocol.

Limited information is available on the feasibility and efficacy of autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients >65 years of age. In 1995-2005, 22 myeloma patients >or=65 years (median 68, eight >or=70) and 79 patients <65 years (median 57) were included in an identical treatment protocol. The first progenitor cell mobilization with cyclophosphamide plus granulocyte-colony stimulating factor (G-CSF) was successful in 95 and 96% of the patients, respectively. To date, 92 patients have received MEL (melphalan) 200 mg/m2 supported by ASCT. No early treatment-related deaths were observed among 22 elderly patients, whereas one younger patient died early. Engraftment and the need for supportive care were comparable between groups. The elderly patients tended to have more WHO grade 3-4 oral or gastrointestinal toxicity when compared to the younger patients (45 vs 23%, P=0.06). After ASCT, a complete response was observed in 44% of the elderly patients and 36% of the younger patients, respectively. No difference was observed between these age groups in progression-free survival (23 vs 21 months) or overall survival (57 vs 66 months) after ASCT. We conclude that MEL200 is a safe and efficacious treatment in selected elderly myeloma patients.

Adult↗
PubMed2004

Prediction of mobilisation failure in patients with non-Hodgkin's lymphoma.

Factors affecting progenitor cell mobilisation in patients with non-Hodgkin's lymphoma (NHL) are incompletely understood. We have analysed factors predicting mobilisation failure in 97 consecutive patients with NHL (59 males, 38 females; median age 49 years) who received mobilisation with intermediate-dose CY (4 g/m(2)) followed by G-CSF. The histology included large cell B (N=50), mantle cell (N=16), follicular (N=16) and other NHL (N=15). The disease status was 1CR/PR/primary refractory in 66 patients and >1 CR/PR in 31 patients. The minimum criterion for successful mobilisation was the collection of >or=1.5 x 10(6)/kg CD34(+) cells. In all, 18 patients (19%) failed to reach this threshold. In univariate analysis, premobilisation factors associated with mobilisation failure included BM involvement at the time of diagnosis (P=0.001) or prior to mobilisation (P=0.001) and low platelet count just prior to mobilisation (P=0.001). In multivariate analysis, only BM involvement at diagnosis (P=0.004) and platelet count just prior to mobilisation (P=0.01) were associated with mobilisation failure. A mathematical model based on these two factors and presented in the form of a receiver operating characteristics curve showed a sensitivity of 0.71 and a specificity of 0.77 in the prediction of mobilisation failure. Patients at a high risk of mobilisation failure may benefit from novel approaches.

Adolescent↗
PubMed2003

Low-dose or intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor for progenitor cell mobilisation in patients with multiple myeloma.

Cyclophosphamide (CY) combined with granulocyte colony-stimulating factor (G-CSF) is commonly used to mobilise blood progenitor cells to support high-dose therapy in patients with multiple myeloma (MM). The optimal dose of CY in this setting is unknown. We have retrospectively analysed mobilisation efficiency and need for supportive care in 57 patients with newly diagnosed myeloma previously treated with VAD+/-local radiotherapy. The patients were mobilised either with low-dose CY (LD-CY, 1.2-2 g/m(2)) (n=25) or intermediate-dose CY (ID-CY, 4 g/m(2)) (n=32) plus G-CSF. Both regimens proved to be effective in the progenitor cell mobilisation. At least 2 x 10(6)/kg CD34+ cells were collected from 88% and 84% of the patients with a single apheresis, respectively. Only one patient in the LD-CY group (4%) failed to mobilise vs none in the ID-CY group. Patients mobilised with LD-CY plus G-CSF had less toxicity: fewer hospital days during the mobilisation and apheresis procedures (5 vs 9 days, P<0.001), lower frequency of fever (20 vs 73%, P<0.001) and less need for supportive care including platelet transfusions (0 vs 24%, P=0.004) and days on parenteral antibiotics (0 vs 4 days, P<0.001). While these regimens seem to be equally effective in terms of progenitor cell mobilisation in newly diagnosed patients with MM, LD-CY+G-CSF is preferential because of more optimal resource utilisation and more favourable toxicity profile.

Adult↗
PubMed2003

Multiple complete remissions in a patient with acute myeloid leukemia (M4eo) with low-dose cytosine arabinoside and all-trans retinoic acid.

A 54-year-old female with acute myeloid leukemia (AML) (FAB M4eo) was treated at second relapse with a combination of low-dose cytosine arabinoside (LDAraC) (20 mg b.i.d. subcutaneously) and all-trans retinoic acid (ATRA) (45 mg/m2/d orally) on days 1-10. The patient achieved a complete hematological remission after the first cycle and was consolidated with three similar cycles at four-week intervals. Subsequently, the patient relapsed several times. Altogether seven complete hematological remissions including some cytogenetic remissions were induced with the same regimen. The patient survived 81 months after the start with LDAraC-ATRA regimen. This low-toxicity regimen may be useful in some patients with poor-risk AML.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Effects of gestational age and prenatal and perinatal events on the coagulation status in premature infants.

OBJECTIVE: To study prospectively the effects of prematurity and perinatal events on the coagulation status of premature infants. PATIENTS AND MAIN OUTCOME MEASURES: Blood samples from premature infants born before 37 gestational weeks were taken for analysis of coagulation factors II, V, VII, and X and platelet count. RESULTS: A total of 125 premature infants, 71 boys, were studied at the median postnatal age of 40 minutes (range 12-100). The lowest median activities of coagulation factors II, V, VII, and X and the platelet count were observed, as expected, in infants (n = 21) born at 24-27 weeks gestation. Twin B (n = 14) had lower median activities of coagulation factors II, V, VII, and X than twin A. Infants with evidence of mild asphyxia (Apgar score at 5 minutes < 7 or cord pH < 7.26) had significantly (p < 0.05) lower levels of coagulation factors II, V, VII, and X and platelet counts than infants without asphyxia. Infants who were small for gestational age (SGA) had significantly (p < 0.05) lower levels of coagulation factors V and VII and platelet counts than infants of appropriate size for gestational age. Other prenatal and perinatal variables examined (sex, maternal hypertension and/or pre-eclampsia, antenatal steroid use, mode of delivery, Apgar scores) did not show any significant associations with coagulation status, which may be explained by the small number of infants studied. CONCLUSIONS: The data strongly suggest that there are distinct differences in specific coagulation tests in different patient populations, which could assist in the identification of extremely preterm, SGA, or asphyxiated preterm infants who may be susceptible to haemorrhagic problems perinatally.

Asphyxia Neonatorum↗
PubMed2000

Comparative genomic hybridization reveals frequent losses of chromosomes 1p and 3q in pheochromocytomas and abdominal paragangliomas, suggesting a common genetic etiology.

Pheochromocytomas and abdominal paragangliomas are rare, catecholamine-producing tumors that arise from the chromaffin cells derived from the neural crest. We used comparative genomic hybridization (CGH) to screen for copy number changes in 23 pheochromocytomas and 11 abdominal paragangliomas. The pattern of copy number changes was similar between pheochromocytomas and paragangliomas, with the most consistent finding being loss of 1cen-p31, which was detected in 28/34 tumors (82%). Losses were also found on 3q22-25 (41%), 11p (26%), 3p13-14 (24%), 4q (21%), 2q (15%), and 11q22-23 (15%), and gains were detected on 19p (26%), 19q (24%), 17q24-qter (21%), 11cen-q13 (15%), and 16p (15%). Losses of 1p and 3q were detected in the majority of tumors, whereas gains of 19p and q, 17q, and 16p were seen only in tumors with six or more CGH alterations. This progression of genetic events did not correspond with the conversion to a malignant phenotype. CGH alterations involving chromosome 11 were more frequent in the malignant tumors, compared with the benign tumors (9/12 versus 3/16). In summary, we propose that pheochromocytomas and abdominal paragangliomas, which share many clinical features, also have a common genetic origin and that the loss of 1cen-p31 represents an early and important event in tumor development.

Abdominal Neoplasms↗
PubMed2000

Feasibility and toxicity of high-dose chemotherapy supported by peripheral blood stem cell transplantation in elderly patients (>/=60 years) with non-Hodgkin's lymphoma: comparison with patients <60 years treated within the same protocol.

Limited data are available concerning feasibility and toxicity of progenitor cell mobilization and high-dose therapy (HDT) supported by peripheral blood stem cell transplantation (PBSCT) in elderly patients (>/=60 years) with non-Hodgkin's lymphoma (NHL). From 1995 to 1999, 17 elderly NHL patients (median age 63 years, range 60-70) entered our HDT program and were mobilized with CY (4 g/m2) followed by G-CSF. Mobilization was successful in 13 patients, who then received BEAM or BEAC followed by PBSCT. The feasibility and toxicity of progenitor cell mobilization and HDT in the elderly patients were compared with experiences in 62 NHL patients <60 years (median 46 years, range 16-59), who received the same mobilization protocol and of whom 48 patients received HDT supported by PBSCT. No significant differences were observed between these groups in the success rate of progenitor cell mobilization, in the number of CD34-positive cells collected or in the number of aphereses needed. HDT appeared to be somewhat more toxic in the elderly patients: a higher peak CRP value (P = 0.08) and longer in-hospital stay (P = 0. 05) were observed. No differences were found in transplant-related mortality or severe organ toxicity between these age groups except for oral mucositis grade >2, which tended to be more common in the elderly patients (P = 0.07). We conclude that progenitor cell mobilization and HDT supported by PBSCT is also feasible in selected elderly patients with NHL. Bone Marrow Transplantation (2000) 26, 737-741.

Adolescent↗
PubMed2000

Autologous peripheral blood stem cell transplantation in a patient with severe mixed connective tissue disease.

A 65-year old man with mixed connective tissue disease (MCTD) and severe therapy resistant polymyositis was considered for high-dose cyclophosphamide (200 mg/kg) supported by autologous stem cell transplantation (ASCT). During a 21 months follow-up there has been a significant subjective, but objectively only a slight improvement in muscle strength. Initially the levels of serum creatine kinase and serum aldolase normalised, but are at 21 months at about the same level as before ASCT. Based on histopathological examination there is still active myositis. Our case would suggests that this treatment may have some efficacy in MCTD with severe polymyositis although longer follow-up is needed.

Aged↗
PubMed1999

Hormone therapy failure in human prostate cancer: analysis by complementary DNA and tissue microarrays.

BACKGROUND: The molecular mechanisms underlying the progression of prostate cancer during hormonal therapy have remained poorly understood. In this study, we developed a new strategy for the identification of differentially expressed genes in hormone-refractory human prostate cancer by use of a combination of complementary DNA (cDNA) and tissue microarray technologies. METHODS: Differences in gene expression between hormone-refractory CWR22R prostate cancer xenografts (human prostate cancer transplanted into nude mice) and a xenograft of the parental, hormone-sensitive CWR22 strain were analyzed by use of cDNA microarray technology. To validate the data from cDNA microarrays on clinical prostate cancer specimens, a tissue microarray of specimens from 26 prostates with benign prostatic hyperplasia, 208 primary prostate cancers, and 30 hormone-refractory local recurrences was constructed and used for immunohistochemical detection of protein expression. RESULTS: Among 5184 genes surveyed with cDNA microarray technology, expression of 37 (0.7%) was increased more than twofold in the hormone-refractory CWR22R xenografts compared with the CWR22 xenograft; expression of 135 (2.6%) genes was reduced by more than 50%. The genes encoding insulin-like growth factor-binding protein 2 (IGFBP2) and 27-kd heat-shock protein (HSP27) were among the most consistently overexpressed genes in the CWR22R tumors. Immunohistochemical analysis of tissue microarrays demonstrated high expression of IGFBP2 protein in 100% of the hormone-refractory clinical tumors, in 36% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). Overexpression of HSP27 protein was demonstrated in 31% of the hormone-refractory tumors, in 5% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). CONCLUSIONS: The combination of cDNA and tissue microarray technologies enables rapid identification of genes associated with progression of prostate cancer to the hormone-refractory state and may facilitate analysis of the role of the encoded gene products in the pathogenesis of human prostate cancer.

Animals↗
PubMed1999

Acquired X-chromosome aneuploidy in children with acute lymphoblastic leukemia.

BACKGROUND: A cytogenetic study of 75 consecutive children with ALL revealed a normal karyotype, a low hyperdiploid karyotype (including 47-50 chromosomes), and a high hyperdiploid karyotype (including > 50 chromosomes) in 10, 12, and 33 patients, respectively. An acquired extra X-chromosome was detected at diagnosis by conventional cytogenetics in 29 (88%) of 33 children with a high hyperdiploid karyotype and in 4 (33%) of 12 children with a low hyperdiploid karyotype. X-chromosome aneuploidy was retrospectively studied by fluorescence in situ hybridization (FISH) in eight and 20 patients with a normal and a hyperdiploid karyotype, respectively. PROCEDURE: A classical cytogenetic study was performed according to standard methods. FISH with the centromeric probe specific to X-chromosome was used to study interphase cells of bone marrow or blood samples. RESULTS: An extra X-chromosome was found by FISH in all 13 patients with a high hyperdiploid or tetraploid, in 6 of 7 patients with a low hyperdiploid, and in none with a normal karyotype. Two children with a normal karyotype displayed monosomy X. Altogether, 57.3% of newly diagnosed children displayed X-chromosome aneuploidy. CONCLUSIONS: Out study indicates that X-chromosome aneuploidy may be the most common chromosome abnormality in childhood ALL. It can be detected in nearly all children with a high hyperdiploid karyotype and up to one-half of the patients with a low hyperdiploid karyotype. FISH with an X-chromosome centromeric probe is a rapid and simple tool to detect an abnormal clone at diagnosis in the majority of children with ALL and is useful in confirming remission in these patients.

Adolescent↗
PubMed1999

Comparative genomic hybridization and conventional cytogenetic analyses in childhood acute myeloid leukemia.

Comparative genomic hybridization (CGH) analysis was performed on bone marrow specimens from 19 children with acute myeloid leukemia (AML) at diagnosis. The results of CGH were compared to those of conventional cytogenetic analysis. The most common CGH aberrations were gains of whole chromosomes 6 and 8, both of which appeared three times. Two losses were seen twice; losses of whole chromosomes 7 and X. The CGH findings were concordant with the results of conventional karyotyping. CGH did not add new information to the karyotypes. Since no high-level amplification was found among the samples and standard karyotyping was highly successful, we do not advocate routine use of CGH in the diagnostic evaluation of childhood AML.

Acute Disease↗
PubMed1998

DNA copy number changes in childhood acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVE: Comparative genomic hybridization (CGH) allows the study of DNA copy number changes in a single hybridization from tumor DNA without any cell culture. Three reports of childhood acute lymphoblastic leukemia (ALL) studied by CGH have been published so far, with somewhat discrepant results. In the present study we performed CGH analysis on 36 patients with childhood ALL. The results were compared to those reported earlier on 157 cases. DESIGN AND METHODS: DNA was extracted from bone marrow specimens from 36 patients with childhood ALL. The tumor and reference DNAs were labeled with fluorescein-isothiocyanate conjugated dCTP and dUTP, and Texas red-conjugated dCTP and dUTP. The hybridizations were analyzed using the ISIS digital image analysis system. RESULTS: The most commonly gained chromosomes were X (42%), 4 (31%), 6 (31%), 10 (36%), 14 (28%) and 18 (33%), and the most common losses were at 9p22-pter (6%) and 12p13-pter (14%). INTERPRETATION AND CONCLUSIONS: The pattern of gains of DNA sequences was very similar in the four reports, but the 9p and 12p deletions were observed only in the present study and one previous report. Our review of the results of 193 patients studied so far shows that the success rate using CGH was close to 100%, whereas cytogenetic analysis failed to reveal any information in 21 patients (11%). Furthermore, in 69 (36%) out of 193 patients CGH gave additional information to the banding analysis. CGH should, therefore, be used to supplement standard cytogenetics in the analysis of childhood ALL patients.

Adolescent↗
PubMed1996

Detection of numerical chromosome abnormalities by FISH in childhood acute lymphoblastic leukemia.

Fluorescence in situ hybridization (FISH) was performed on interphase bone marrow cells to study numerical chromosome abnormalities in childhood acute lymphoblastic leukemia (ALL). Ten patients were selected for this study on the basis of having an extra chromosome 6 in the abnormal clone of the bone marrow at diagnosis. The numerical changes that were detected by FISH with a chromosome 6 specific alpha-satellite DNA probe correlated well with the cytogenetic and clinical data in all patients. Three hybridization signals were seen in 43.8--83.0% of interphase cells in the specimens with a hyperdiploid karyotype. The diagnostic bone marrow sample of the patient with a tetraploid karyotype revealed four signals in 67.0% of cells. Two signals were detected in the majority of the cells in the three nonleukemic control bone marrow samples (97.0--97.7%), assessing the cut-off value of about 1% for trisomy 6. This study demonstrates that FISH analysis is a useful and sensitive tool to screen for the presence of extra chromosomes in interphase cells and is important clinically for evaluating the achievement and maintenance of remission in hyperdiploid childhood ALL. However, to detect structural chromosome aberrations which carry important diagnostic and prognostic information, as seen in our patient with the translocation t(1;19) at diagnosis but not at relapse, conventional cytogenetic analysis should be performed both at diagnosis and at relapse.

Adolescent↗
PubMed1994

Cell lineage involvement of recurrent chromosomal abnormalities in hematologic neoplasms.

Analysis of most hematologic neoplasms indicates the involvement of one or more cell lineages in the bone marrow and/or the blood but rules out the involvement of all lineages in any one neoplasm. It is important to detect lineage involvement in order to clarify which stem cells are involved in leukemia, to predict prognosis, and to select appropriate treatment. Our aim was to study the cell lineage involvement of some of the recurrent chromosomal abnormalities seen in hematological neoplasms. The direct morphology-antibody-chromosomes (MAC) method was used. The deletion 20q in myeloproliferative diseases (MPD), the deletion of 5q and t(1;7) in myelodysplastic syndromes (MDS), and t(3;3) in acute myeloid leukemia subtype M7 (AML-M7) were seen in all or at least in two myeloid lineages. These were interpreted as stem cell abnormalities. Deletion 13q in MPD, t(8;21) in AML-M2 and t(15;17) in AML-M3 were seen in granulocytic lineages only; t(14;18) in non-Hodgkin's lymphoma and trisomy 12 as the sole abnormality in chronic lymphocytic leukemia (B-CLL) were seen only in immunoglobulin light chain clonal B cells; inversion 14 in T-CLL was seen only in T cells, whereas t(15;14) in acute lymphocytic leukemia with eosinophilia (ALL-EO) was seen in lymphoid stem cells but not in mature granulocytes or lymphocytes. Additional abnormalities (in addition to the Philadelphia chromosome) in chronic myeloid leukemia (CML) were seen in all myeloid cell lineages and also in mature granulocytes, B cells, and large granular lymphocytes. Abnormalities in Hodgkin's disease were restricted to CD30-positive Reed-Sternberg cells. Trisomy 8 and monosomy 7 are abnormalities that may be present in either stem cells or any of the single cell lineages.

Blast Crisis↗
PubMed1994

Multiple karyotypic abnormalities in three cases of small cell variant of T-cell prolymphocytic leukemia.

Cytogenetic, clinical, and laboratory findings of three patients with a small cell variant of T-cell prolymphocytic leukemia (T-PLL) are presented. Immunophenotypic studies of the morphologically typical small cell variant prolymphocytes showed a mature helper T-cell phenotype (CD4+CD8-) in one patient and a common thymocyte phenotype (CD4+ CD8+) in two other patients. The cytogenetic analysis revealed complex karyotypes with several structural aberrations in the peripheral blood lymphocytes of all three patients. In all cases chromosome 14 was affected with the breakpoint at 14q11. Inversion (14) and isochromosome 8q, often reported as an additional aberration in T-PLL, were detected in two of the patients. In two patients a translocation of the short arm of chromosome 12 was also seen. The T-cell receptor beta-chain gene showed a clonal rearrangement in all three patients, whereas no rearrangements were detected in the immunoglobulin genes. The survival of the patients ranged from 10 weeks to 48 months. The association between cytogenetic, clinical, and laboratory data is discussed.

Adult↗