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M Suttorp

Publications and source records attributed to M Suttorp.

At least 37 records · Page 2Linked to original sources
PubMed1999

Comparative effects of hydrofluoroalkane and chlorofluorocarbon beclomethasone dipropionate inhalation on small airways: assessment with functional helical thin-section computed tomography.

A double-blind, randomized, parallel-group pilot study compared the relative efficacy of hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP [QVAR]; mass median aerodynamic diameter, 0. 8-1.2 m) versus cholorofluorocarbon-11/12 BDP (CFC-BDP [Beclovent]; mass median aerodynamic diameter, 3.5-4.0 m) in 31 steroid naive patients with mild to moderate asthma (PC(20,) 4 mg/mL). Functional high-resolution computed tomography was used to assess the relative efficacy of HFA-BDP and CFC-BDP on regional air trapping, as an indirect measure of small airways function and on regional hyperreactivity. Pretreatment functional computed tomography was performed at residual volume before and after methacholine challenge. After 4 weeks of treatment, functional imaging was repeated before and after the same concentration of methacholine that was administered before the treatment (n = 19 patients). Quantitative assessment of changes in distribution of lung attenuation was performed. After 4 weeks of treatment, the HFA-BDP group showed significantly more improvement in air trapping overall (a shift in the lung attenuation curve at residual volume toward more attenuation) on the posttreatment computed tomography scan (P <.05; Fisher's Exact Test). After an equal constrictor stimulus (methacholine concentration), subjects treated with HFA-BDP (n = 10 patients) showed less increase in air trapping overall than subjects treated with CFC-BDP (n = 9 patients) on the posttreatment scans compared with the pretreatment scans (P <.001; Fisher's Exact Test). No significant difference was demonstrated between the 2 treatment groups with respect to improvement in symptoms, spirometry, or methacholine responsiveness assessed by FEV(1), except for a greater reduction in breathlessness in the HFA-BDP group (P <.05). We conclude that HFA-BDP may have greater efficacy in the peripheral airways and that this effect is better assessed with functional imaging computed tomography techniques than with conventional physiologic tests.

Administration, Inhalation↗
PubMed1999

Autografting of highly purified peripheral blood progenitor cells following myeloablative therapy in patients with lymphoma: a prospective study of the long-term effects on tumor eradication, reconstitution of hematopoiesis and immune recovery.

In a prospective study, we have investigated CD34+ selection of peripheral blood progenitor cells (PBPC) for autotransplantation in patients with lymphoma. Twenty-six consecutive patients (10 follicular lymphomas, seven mantle cell lymphomas, seven B-CLL, two immunocytomas) were mobilized using chemotherapy plus G-CSF. Sufficient numbers of PBPC could be collected from 24 patients and were immunoselected with the semiautomated Isolex 300 (n = 17) or the fully integrated Isolex 300i (n = 7) devices. The selection products were assayed by PCR amplification of clonal CDRIII or t(14;18) rearrangements for residual tumor cell content. Residual disease and long-term hematopoietic and immune recovery were studied by assessing the following parameters at 3, 6, and 12 months post-transplant: CDRIII or t(14;18) PCR, platelet count, lymphocyte subsets, serum IgG, serum IgA, and measles titer. With the Isolex 300 device 26% (10-65) of input CD34+ cells were recovered with a median purity of 89.2% (49.4-98.9) after CD34+ selection. The Isolex 300i device allowed significantly better recoveries (46% (22-86)) and purities of CD34+ cells (98.8% (92.2-99.2)). The overall purging efficacy was 3.2 (0.6-5.1) log. Twenty patients have been reinfused with CD34+ selected grafts after myeloablative preparation. Rapid engraftment occurred in all patients. With a median follow-up of 28 (19-42) months, 14 patients are alive without clinical or molecular evidence of disease recurrence, whereas five have relapsed and one additional patient shows persistent presence of the disease-specific molecular marker without clinical progression. Cellular and serological parameters of hematopoietic and immune functions were largely normal at 12 months post-transplant including the measles titer which was present in all patients. Kinetics of immunohematopoietic recovery were similar to those of 12 control patients who had received unmanipulated PBPC during the same time period except for the recovery of CD4+ CD45RA+ T cells which was significantly delayed in the CD34+ group. During the first year post-transplant, transient monoclonal or oligoclonal gammopathies were observed in seven of 16 study patients. We conclude that CD34+ selection with the Isolex system allows preparation of highly purified CD34+ fractions and effective tumor cell depletion. The CD34+ products can be reinfused safely after myeloablative treatment and result in sustained hematopoietic and immune recovery. The fact that all patients retained their specific measles immunity suggests that myeloablative treatment with reinfusion of highly purified CD34+ PBPC is not immunoablative.

Adult↗
PubMed1998

Comparison of different strategies of molecular genetic monitoring following autologous stem cell transplantation in patients with follicular lymphoma.

Two different molecular genetic methods were compared for their suitability for monitoring minimal residual disease in patients with follicular lymphoma (FL) treated with high-dose therapy and autologous stem cell transplantation. Fifteen patients were selected because of a specific PCR-amplifiable t(14;18) mbr translocation. PCR amplification of rearrangements of the complementary region III (CDRIII) of the immunoglobulin heavy chain gene was also carried out. After autologous stem cell transplantation, patients were prospectively monitored with both molecular genetic methods. Seven of the 15 patients with detectable t(14;18) prior to transplantation were persistently negative during follow-up to 32 months post transplant. None of these patients relapsed, whereas four of eight patients with positive PCR signals post transplant relapsed. Comparing t(14;18) and PAGE results, we observed six patients showing clonal signals in CDRIII PAGE in spite of persistent negativity of t(14;18) PCR. We concluded that in patients with FL, t(14;18) PCR is superior to CDRIII PCR in terms of sensitivity and specificity. A positive t(14;18) PCR during the first year post transplant is highly predictive for disease recurrence. CDRIII PCR may be used for monitoring in t(14;18) negative lymphomas. However, due to the poor specificity of conventional gel electrophoresis PCR, the use of clone-specific probes is highly desirable.

Adult↗
PubMed1997

Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation.

Donor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone marrow transplantation (BMT). Severe graft-versus-host disease and prolonged periods of pancytopenia compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent some of the problems associated with DLI. Eleven patients (median age 41 years) received a total of 20 donor cell infusions. Their diagnosis was CML in hematological (two patients) or cytogenetic relapse (two patients), six patients suffered from acute myeloid leukemia (AM; n = 5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+). One patient had multiple myeloma (MM). All six patients with acute leukemias received cytoreductive therapy prior to PBPC infusions; three patients with CML were pretreated with IFN alpha. Four of four patients with CML responded to PBPC infusions and currently are in complete clinical and molecular remission for time periods between 1 and 12 months. Six of six patients with acute leukemias achieved a complete remission. All of them relapsed after a median remission duration of 24 weeks (range 11-49 weeks). Three patients relapsed at extramedullary sites (CNS, testes, skin). Four of six acute leukemia patients received further cytoreductive therapy. All patients responded again and are in complete remission for time periods between 14 and 615 days. Two patients with acute leukemias have died due to dissemination of the disease. The patient with MM did not respond and is alive with disease. Severe (grade III) acute GVHD developed in two of 11 patients, three patients developed grade II disease, six patients did not show any signs of GVHD. Extensive chronic GVHD has developed in two cases to date. Patients with chemotherapy prior to PBPC infusion developed neutropenia and thrombocytopenia with a maximum duration of 20 and 14 days, respectively; prolonged periods of neutropenia did not occur. Two patients developed long-lasting thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted in only limited duration of cytopenia. The usage of PBPC infusion instead of non G-CSF-mobilized donor cells for treatment of relapse after BMT may reduce pancytopenia-related complications and merits further investigation.

Adult↗
PubMed1997

Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.

PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS: Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION: Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.

Bone Marrow Transplantation↗
PubMed1996

Precast commercial polyacrylamide gels for separation of DNA amplificates by temperature gradient gel electrophoresis: application to clonality analysis of lymphomas.

The third complementary determining region (CDR-III) of the rearranged immunoglobulin heavy chain (IgH) genes represents a unique marker for a lymphocyte and its clonal descendants and can be amplified by the polymerase chain reaction (PCR) technique. This approach has markedly enhanced the sensitivity for detection of clonal lymphocyte populations in patients with malignant B-lymphoid neoplasias. To monitor minimal residual disease (MRD) in tissue specimens during or after antineoplastic treatment, the problem of detecting the presence of a few clonal (malignant) lymphocytes in coexistence with a majority of polyclonal lymphocytes has to be addressed. Semi-nested PCR amplification of CDR-III rearrangements from specimen infiltrated by tumor cells generates clonal signals in front of a polyclonal background, and therefore high resolution electrophoretic techniques for separation of DNA fragments are required. Temperature gradient gel electrophoresis (TGGE) resolving DNA homo- and heteroduplexes according to their thermal stability has been successfully applied for this purpose using special electrophoretic equipment. We describe an adjustment to this technique by using a commercially available precast 0.5 mm thick polyacrylamide gel and by changing a standard horizontal electrophoretic device into a TGGE device. By this means we screened patients with B-cell lymphoma undergoing high-dosage radiochemotherapy followed by autologous transplantation for continuous presence of clonal (tumor-specific) CDR-III rearrangements. Specimens from blood and bone marrow were collected on diagnosis as well as before and after autologous transplantation. In addition, the autograft (bone marrow or peripheral blood hematopoietic stem cells) was analyzed. Tumor cells were easily detected in the transplants and in specimens collected during follow-up examinations. The clinical value of these findings remains unclear as yet because the number of cases investigated was small and the follow-up time is still too short. However, we conclude that the technique of combining the sensitivity of PCR with the specificity of high resolution TGGE is easy to use, making it possible to handle, in a clinical routine, a great number of samples within a short time in order to monitor MRD in patients with B-cell neoplasias.

Cell Transplantation↗
PubMed1996

Can blood group O red cells of donor origin acquire weak group A reactivity through serum A transferase of the recipient after bone marrow transplantation?

BACKGROUND: Blood group A substance was detected on red cells of a patient who received a bone marrow transplant from a blood group O donor 3.5 years ago. MATERIALS AND METHODS: Peripheral blood was investigated by conventional serological techniques, fluorescence in situ hybridisation, and polymerase chain reaction. RESULTS: All peripheral blood cells are of donor origin. Anti-A and not anti-A, B of blood group O individuals can be absorbed to the group O red cells of the patient. CONCLUSION: We suppose that the patient's residual serum A transferase attaches the appropriate sugar to substance H on the red cell membrane to form substance A.

ABO Blood-Group System↗
PubMed1995

Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor)

Transplantation of allogeneic peripheral blood progenitor cells (PBPCs) may have advantages over bone marrow transplantation (BMT) with regards to the speed of hematopoietic and immunologic recovery, which may then shorten the time spent in hospital and decrease costs. The recipient might also profit by an enhanced graft-versus-leukemia reaction exerted by the high number of natural killer cells contained in such grafts. The donor could be spared the discomfort and risks of general anesthesia and marrow harvesting. Primary transplantation of unmanipulated allogeneic PBPCs has not been reported so far because the vast amount of T cells contained in the collection product was thought to cause severe graft-versus-host disease. We present preliminary data on primary transplantation of allogeneic PBPCs in patients who either suffered from advanced leukemia or had a donor unable to undergo general anesthesia. Eight patients with a median age of 42 years suffering from acute myelogenous leukemia (AML) in first remission (n = 3), AML in third remission, AML in relapse (n = 2), acute lymphoblastic leukemia in second remission, or chronic myelogenous leukemia in accelerated phase received myeloablative therapy followed by transplantation of unmanipulated allogeneic PBPCs mobilized with granulocyte colony-stimulating factor (5 to 10 micrograms/kg of body weight of filgrastim administered for 5 to 6 days) in their HLA-identical donors. Hematopoietic reconstitution was achieved in all patients with a median of 15.5 (16.5) days after transplant needed to surpass an absolute neutrophil count of 0.5 (1.0) x 10(9)/L. The median time to an unsupported platelet count greater than 20 (> 50) x 10(9)/L was 19.5 (41) days after grafting. Three patients did not exhibit signs of acute graft-versus-host disease (GVHD), grade I disease was seen in one patient, and three patients experienced grade II disease limited to the skin. The only patient with severe acute GVHD (grade III) refused to take his oral cyclosporin regularly and had ineffective serum levels for most of the time until relapse. Six of eight patients are currently alive without evidence of disease between 61 and 533 days after grafting; two patients grafted for AML in relapse achieved a complete remission after transplantation but relapsed again and died of leukemia on days +48 and +70, respectively. Primary transplantation of unmanipulated allogeneic PBPCs is feasible and results in long-term engraftment without causing detrimental GVHD.

Adolescent↗
PubMed1995

Identification and structural analysis of rearranged immunoglobulin heavy chain genes in lymphomas and leukemias.

The third complementarity determining region (CDR3) of the hypervariable domain of immunoglobulin heavy chain (IgH) genes represents a highly variable and clone-specific IgH-CDR3 sequences in 10 non-Hodgkin's lymphomas (NHL), five chronic lymphocytic leukemias (CLL) and five acute lymphoblastic leukemias (ALL) of B cell lineage. The IgH-CDR3 sequences were amplified using DNA extracted from clinical specimens (bone marrow, peripheral blood and fresh-frozen or paraffin-embedded lymph nodes) by a semi-nested PCR with consensus primers directed to conserved regions within the variable (VH) and the joining (JH) gene segments. In 17/20 samples (85%), a distinct IgH-CDR3 PCR product was obtained. Individual PCR products were sequenced after cloning. The nucleotide sequences of 134 randomly chosen recombinant vectors were determined demonstrating in 17/20 cases (85%) monoclonal VH-N-DH-N-JH junctions. Analysis of PCR products by temperature-gradient gel electrophoresis (TGGE) confirmed the specificity of the IgH-CDR3 PCR/sequencing results. Moreover, the combination of PCR/TGGE technology allowed the rapid and specific characterization of clonal IgH-CDR3 junctions in B cell proliferations by direct sequencing even in the presence of admixed polyclonal B cells.

Base Sequence↗
PubMed1995

Rapid engraftment of peripheral blood progenitor cell grafts purged with B cell-specific monoclonal antibodies and immunomagnetic beads.

PBPC harvesting was performed in two patients with advanced-stage low-grade non-Hodgkin's lymphoma after mobilization with dexa-BEAM chemotherapy plus G-CSF. The collected grafts were subjected to immunomagnetic purging using B cell-specific moAbs and paramagnetic beads. Immunophenotypic and/or molecular analysis of the resulting products (PCR amplification of t(14;18) or CDR-III rearrangements) demonstrated successful depletion of lymphoma cells. Rapid and durable hematopoietic recovery occurred after reinfusion of the purged grafts following myeloablative radiochemotherapy (9-10 days to neutrophils > 0.5 x 10(9)/l; 9-11 days to platelets > 20 x 10(9)/l). We conclude that effective immunomagnetic purging of PBPC grafts is feasible without affecting engraftment.

Antibodies, Monoclonal↗
PubMed1994

Results of antibiotic treatment of Hickman-catheter-related infections in oncological patients.

A group of 330 oncological patients were supported throughout a 7-year period with central venous catheters (Broviac/Hickman catheters) and underwent standard oncological chemotherapy, because of hematological malignancies or solid tumors (156 children), or a myeloablative conditioning regimen followed by bone marrow transplantation because of leukemia or lymphoma (174 patients: 110 adults, 64 children). Of these, 17 patients (8 after bone marrow transplantation) developed a catheter-related bacteremia and were treated by at least two antibiotics according to the sensitivity of the bacteria. In 1 patient the catheter (infected by Bacillus cereus) was removed on day 25 of antibiotic treatment because of persistent high fever and further positive blood cultures. After bone marrow transplantation, 2 other patients, with a Pseudomonas or a Staphylococcus infection respectively, did not respond to the combined antibiotic treatment and died 1 week and 7 weeks later, respectively, from transplant-related severe graft-versus-host disease. In the other 14 patients antibiotic treatment was successful and removal of the central-vein catheter could be avoided.

Adult↗