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Biomedical subjects

K Laczika

Publications and source records attributed to K Laczika.

43 records · Page 3Linked to original sources
PubMed1994

AML1/ETO fusion mRNA can be detected in remission blood samples of all patients with t(8;21) acute myeloid leukemia after chemotherapy or autologous bone marrow transplantation.

The chromosomal translocation t(8;21)(q22;q22) in acute myeloid leukemia (AML) can be detected by a reverse transcription-polymerase chain reaction (RT-PCR) for the chimeric AML1/ETO transcript. We have evaluated the clinical relevance of this method for monitoring and detection of minimal residual disease (MRD) in seven patients who reached a complete hematological remission (CHR) after chemotherapy or autologous bone marrow transplantation (ABMT). Peripheral blood (PB) samples of five patients in first continuous complete remission (CCR) were still PCR-positive at a frequency of 1 in 10(5) cells after 7, 8, 8, 10 or 66 months. Chemotherapy led to a reduction from first- to second-step PCR-positivity in three serially monitored patients. AML1/ETO mRNA was also detected in the PB of two patients in CCR, 10 or 12 months after ABMT. PB and bone marrow (BM) showed identical results in all samples tested simultaneously. AML1/ETO fusion transcripts were neither found in the PB and BM of a healthy individual, nor in the PB of a patient after allogeneic BMT for cytogenetically proven t(8;21)-leukemia. Our results indicate the presence of cells carrying the AML1/ETO rearrangement in the PB and BM of all patients in CHR after chemotherapy or ABMT for t(8;21)-positive AML. While this finding raises interesting questions about the biology of acute leukemia, it limits the value of the AML/ETO RT-PCR for the prediction of impending relapse.

Adult↗
PubMed1994

Rapid achievement of PML-RAR alpha polymerase chain reaction (PCR)-negativity by combined treatment with all-trans-retinoic acid and chemotherapy in acute promyelocytic leukemia: a pilot study.

The reverse transcriptase-polymerase chain reaction (RT-PCR) for the fusion transcript of PML-RAR alpha can be used to detect minimal residual disease (MRD) in acute promyelocytic leukemia (APL). We have applied a semi-quantitative two-step PCR assay (sensitivity: step 1 = 1 in 10(3) cells; step 2 = 1 in 10(6) cells) to monitor the dynamics of MRD after combined therapy with all-trans-retinoic acid (ATRA) and chemotherapy (CT) in 5 patients in whom complete clinical remission (CR) was achieved. The patients received an induction treatment with ATRA for 47, 40, 38, 14 or 10 days. In three patients ATRA was followed by CT. Two patients with hyperleukocytosis at diagnosis or after ATRA received an overlapping CT starting from day 3 or 7. Four of the five patients became two-step PCR-negative in their bone marrow within 43 to 82 days after onset of therapy. Two-step PCR-negatively was achieved with ATRA plus one course of CT in these four patients who are still in continuous complete remission after 19, 18, 7 and 5 months. One of these patients did not even receive consolidation CT because of congestive heart failure. The fifth patient remained second-step PCR-positive and relapsed after 5 months. Our results indicate that the combined regimen can rapidly reduce MRD below a detection limit of 1 in 10(6) cells within 1-3 months and that these results can even by achieved by a short course of ATRA together with only one cycle of CT.

Aged↗
PubMed1993

Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL).

Our purpose was to evaluate the ability of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemotherapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemotherapy according to the BMFT protocol and received in addition r-metHuG-CSF (200 micrograms/m2/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/microliters at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500/microliters) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/microliters) in G-CSF-treated patients compared with controls (1880/microliters). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemotherapy could be given on time to 11/13 (85%) G-CSF patients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.

Adolescent↗
PubMed1991

Hepatic and splenic abscesses--a common complication of intensive chemotherapy of acute myeloid leukemia (AML). A prospective study.

In order to determine the frequency of hepatosplenic abscesses in AML patients during chemotherapy and to evaluate the clinical and laboratory characteristics of this complication we performed a prospective study over a 28-month period. Fifty-five consecutive patients with de novo AML or relapse who received intensive chemotherapy underwent regular ultrasound examinations. In 16 patients (29.1%) hepatic and/or splenic abscesses were detected sonographically. Histopathological evidence for abscess formation was obtained in five of these 16 patients. In three patients granulation tissue and in one patient necrotizing granulomas were found. Causative micro-organisms were proven in only three patients: Candida hyphae were demonstrated in one patient, gram-positive cocci in another. Bacteria and fungi were seen in the tissue specimen of the third patient. Patients with hepatosplenic abscesses had significantly prolonged fever after neutrophil recovery but did not differ from patients without abscesses in any other laboratory or clinical features. Due to the absence of specific alerting clinical and laboratory signs and symptoms of hepatosplenic abscesses, routine ultrasound examination is required for detection of this complication. The presence of hepatic and/or splenic abscesses does not necessarily worsen the prognosis, but it may influence the decision on further chemotherapy and antimicrobial treatment.

Abscess↗
PubMedDate not supplied

Prospective monitoring of minimal residual disease in acute myeloid leukemia with inversion(16) by CBFbeta/MYH11 RT-PCR: implications for a monitoring schedule and for treatment decisions.

Minimal residual disease in patients with acute myeloid leukemia (AML) with inversion(16) can be monitored by CBFbeta/MYH11 RT-PCR. While the association between molecular remission (MR) in bone marrow (BM) and peripheral blood (PB) and long-term clinical remission (CR) seems to be established, there are insufficient data on the kinetics of CBFbeta/MYH11. We have performed a prospective study in order to generate a reasonable and sufficient schedule for PCR-monitoring. 11 patients with AML and inversion (16) in complete hematological remission have been prospectively monitored by CBFbeta/MYH11 RT-PCR in their BM and PB during an observation period of 7 to 67 months (median 32 months). Patients were followed during consolidation chemotherapy with repetitive cycles of high-dose Ara-C and after autologous or allogeneic stem cell transplantation in 2nd CR or refractory AML. MR never coincided with achievement of CR but occurred between 2 and 8 months after hematological remission. All patients in continuous CR were PCR-negative after 1-8 (median 4) months. Two patients relapsed despite MR for 10 to 15 months. Molecular relapse preceded hematological relapse by 3 to 5 months. Three out of four patients who were not in MR after 8 months relapsed. Allogeneic stem cell transplantation was able to eradicate minimal residual disease in 4/4 patients. In 2 patients a temporary reconversion to PCR-positivity was reversed by reduction of immunosuppression. 1 patient did not become PCR-negative until compete withdrawal of immunosuppression. We suggest that BM and PB should be examined after the last consolidation treatment. In case of MR, PB should be examined every 1 to 2 months and BM examination should be done only in case of PCR-positivity in PB in order to confirm the molecular relapse and to identify an impending cytogenetic and/or hematological relapse. CBFbeta/MYH11 RT-PCR monitoring is able to predict relapse 3 to 5 months prior to overt hematological relapse, offers a window of opportunity for preemptive therapy of molecular relapse and confers implications for immunotherapy in the setting of allografting.

Acute Disease↗