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Biomedical subjects

M Kletzel

Publications and source records attributed to M Kletzel.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cytokine-mobilized allogeneic peripheral blood stem cell transplants in children result in rapid engraftment and a high incidence of chronic GVHD.

Between October 1995 and October 1998, 24 children aged 9 months to 17 years (median 11 years) underwent cytokine-mobilized allogeneic peripheral blood stem cell (PBSC) transplantation for treatment of hematological disorders. All of the transplants were the first allogeneic transplant for the recipient. Twenty patients were transplanted for hematological malignancies (ALL = 8, AML = 6, CML = 4, MDS = 2) and four patients were transplanted for non-malignant disease (thalassemia major = 2, Wiskott-Aldrich syndrome = 1, Kostmann's syndrome = 1). Nineteen donors were HLA-identical siblings, four were HLA-matched or single antigen mismatched parents, and one was a syngeneic transplant. Donors aged 8 to 38 years (median 15 years, 14 donors <18 years) received G-CSF 10 microg/kg/day subcutaneously beginning 4 days before PBSC collection and were submitted to one to three leukapheresis collections. The median CD34+ cell yield was 7.8 x 106 cells/kg recipient body weight. All patients achieved an ANC >0.5 x 109/l after a median of 13 days (range 10-21). Twenty-three patients eventually achieved platelet transfusion independence. One patient died on day 63 without ever achieving platelet transfusion independence. Four patients received platelet transfusions to maintain a platelet count well above 20 x 109/l due to bleeding complications. Of the 19 evaluable patients, the median time to a non-transfused platelet count of 20 x 109/l was 12 days (range 0-44). Ten of 23 at-risk patients developed acute GVHD grades II to IV, with grades III to IV in four patients. Twelve of 19 patients followed for at least 100 days have developed chronic GVHD (extensive = 2, limited = 10) with an actuarial risk of chronic GVHD of 75% at 1 year. The Kaplan-Meier estimate of event-free survival is 65% at 2 years. Four patients died (GVHD = 3, VOD = 1), three patients relapsed, and one patient with thalassemia major had a late graft failure with autologous recovery. Based upon our experience, allogeneic PBSCT is safe for both pediatric donors and recipients and engraftment of neutrophils and platelets is rapid. Bone Marrow Transplantation (2000) 25, 13-18.

Adolescent↗
PubMed2000

Analysis of parameters affecting engraftment in children undergoing autologous peripheral blood stem cell transplants.

Eighty-three pediatric patients underwent autologous peripheral blood stem cell transplants at a single institution and were included in a study evaluating the correlations between five engraftment parameters and the time to both neutrophil and platelet recovery. The parameters included: the number of nucleated cells per kg (TNC/kg), the absolute CD34+ cell content per kg (CD34+/kg), the number of mononuclear cells per kg (MNC/kg), the number of BFU-E/kg, and the number of CFU-GM/kg. A two-tailed Mann-Whitney test (alpha = 0.05) was used to determine if there were significant differences between patients with neuroblastoma (n = 45) and patients with other diagnoses (n = 38). No statistically significant differences existed between neuroblastoma patients and patients with other diagnoses. Therefore, the two groups of patients were pooled together. Data were analyzed using both a univariate and multivariate correlation method and Student's t-test (alpha = 0.05). Two statistically significant logarithmic relationships were found. The first relationship was between MNC/kg and time to ANC reconstitution (P = 0.05). The second relationship was between CFU-GM/kg and time to platelet recovery (P = 0.01). Based on the statistical data, we conclude that there is no correlation between nucleated cell dose, CD34+ cell dose, and BFU-E content with either neutrophil or platelet recovery. Accordingly, in this study MNC cell dose per kilogram was the most important parameter predicting the length of time between graft infusion and neutrophil recovery while CFU-GM content per kilogram was the most important parameter predicting the length of time until platelet recovery.

Adolescent↗
PubMed1999

Total body irradiation, cyclophosphamide, and etoposide with stem cell transplant as treatment for infants with acute lymphocytic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) in infants has a very poor outcome with modern chemotherapy. We reviewed our experience with the infants diagnosed with ALL at Children's Memorial Hospital from 1992 to 1997. PROCEDURE: During this time period, 10 infants were diagnosed with ALL. Seven of them were transplanted, four with marrow from HLA-matched siblings and three with umbilical cord blood. Four of the transplanted patients had the MLL gene rearrangement and the other three transplanted patients had one or more other high-risk features including CD10-blasts, age less than 6 months at diagnosis, or prior relapse. The patients were conditioned with a regimen of total body irradiation (TBI), etoposide, and cyclophosphamide (CY). Peritransplant toxicity was tolerable. The graft infused contained a median total nucleated cell dose/kg of 3 x 10(8) (.3 x 10(8)-6 x 10(8)). The median CD34+ cell dose/kg was 5 x 10(6) (.25 x 10(6)-31 x 10(6)). RESULTS: All of the patients engrafted with a median of 18 days (11-29) to reach an absolute neutrophil count (ANC) of 500/microliter. The median time to reach an unsupported platelet count greater than 20,000/microliter was 24 days (18-64). Four of seven of the transplanted patients are leukemia-free survivors at a median follow-up of 775 days. Of the three patients who were not transplanted, one is surviving 2+ years off therapy. CONCLUSIONS: Allogeneic stem cell transplant is an alternative to chemotherapy alone as a treatment for infant ALL when a suitable donor is available.

Age Factors↗
PubMed1999

High-dose chemotherapy followed by peripheral blood stem cell rescue for metastatic rhabdomyosarcoma: the experience at Chicago Children's Memorial Hospital.

BACKGROUND: Because outcome for metastatic rhabdomyosarcoma remains poor with standard therapy, and because some patients with extensive unresectable metastatic rhabdomyosarcoma are unable to tolerate standard therapy with the associated large radiation fields, peripheral blood stem cell rescue (PBSCR) following high-dose chemotherapy was offered as consolidative therapy for patients with Stage 4/Group IV rhabdomyosarcoma. PATIENTS AND METHODS: Eight patients with Stage 4/Group IV rhabdomyosarcoma were diagnosed from May, 1992, through November, 1994. Consolidative PBSCR following thiotepa 300 mg/M2 on days -7, -6, and -5; cyclophosphamide 1,500 mg/M2 on days -5, -4, -3, and -2; and carboplatin 600 mg/M2 on days -3 and -2 was offered to those patients who achieved a complete remission with multimodality therapy. Patients with extensive metastatic disease who did not receive full doses of radiation to all sites of disease remained eligible for high-dose chemotherapy and PBSCR. RESULTS: Five of eight patients achieved a complete response. Four patients underwent PBSCR. One of the four patients is alive without evidence of disease 53 months post-PBSCR. All other patients died of progressive disease. CONCLUSIONS: These results, along with the existing literature, show no advantage of high-dose chemotherapy followed by PBSCR as consolidative therapy for patients with Stage 4/Group IV rhabdomyosarcoma over standard dose chemotherapy, radiation, and surgery. For patients with extensive, unresectable disease at diagnosis who cannot receive radiation to all areas of disease based on concerns of marrow reserve, high-dose chemotherapy followed by PBSCR does not appear to provide adequate local control and cannot be offered as curative therapy.

Adolescent↗
PubMed1999

Indeterminate-cell histiocytosis: immunophenotypic and cytogenetic findings in an infant.

BACKGROUND: The authors report the immunohistochemical, ultrastructural, and cytogenetic findings in a case of malignant histiocytic proliferation in an infant. PROCEDURE: The patient presented initially with bone lesions without skin or systemic involvement. Multiple biopsies were studied extensively by immunohistochemistry and electron microscopy. Cytogenetic studies of cell cultures supplemented with granulocyte-monocyte colony stimulating factor (GM-CSF) were also performed. RESULTS: Morphologically, the cells resembled Langerhans cells, although with greater pleomorphism, as evinced by cells with usual polylobated nuclei. These cells expressed markers for macrophages and antigen presenting cells and were CD1a- and S-100-positive, but lacked Birbeck granules. The cells grown in culture supplemented with GM-CSF showed a unique combination of numerical and structural abnormalities affecting chromosomes 1, 6, 8, and 10. The disease followed a malignant course leading to the patient's demise despite aggressive chemotherapy and bone marrow transplant. CONCLUSIONS: The findings suggest a malignant hematopoietic stem-cell neoplasm with a capacity for macrophage or dendritic-cell differentiation. Morphology and immunophenotypic features place this neoplasm within the group recently conceptualized as indeterminate-cell histiocytosis.

Chromosome Aberrations↗
PubMed1999

Hematopoietic stem-cell transplantation using unrelated cord-blood versus matched sibling marrow in pediatric bone marrow failure syndrome: one center's experience.

Hematopoietic stem-cell transplantation (HSCT) is an effective mode of therapy in pediatrics for the treatment of both malignant and non-malignant disorders. We compared the course of children transplanted with unrelated umbilical cord blood (UCB) to those transplanted with allogeneic sibling bone marrow (BM) for bone marrow failure syndromes. Thirteen patients with a median age of 6.3 years were transplanted for the following diseases between April 1992 and November 1997: myelodysplastic syndromes, aplastic anemia, Diamond-Blackfan anemia, myelofibrosis, paroxysmal nocturnal hemoglobinuria, osteopetrosis and dyskeratosis congenita. The stem cell source was BM in ten patients and UCB in three. We retrospectively examined the conditioning regimens, stem cell source and dose, days to engraftment, survival and complication rate to see whether there was a significant advantage in using one source over the other. The median time to an absolute neutrophil count > 500 per microL was 25 days for UCB patients and 16 days for BM patients. The median time to a platelet count > 20,000 per microL was 55 days for UCB patients and 22 days for BM patients. The 100-day mortality was 66% in UCB patients and 20% in BM patients. The overall mortality rates were 66% and 40%, respectively. Three patients died prior to engraftment. Seven patients (54%) were still alive as of May 1999 with a median follow-up of 1574 days post-transplant. The patients transplanted with BM had faster engraftment and lower rates of graft-versus-host disease, 100-day mortality and overall mortality. HLA-matched sibling BM is preferred as a source but transplantation using unrelated UCB is still an option in treating pediatric bone marrow failure syndromes.

Adolescent↗
PubMed1999

Red cell salvage and reinfusion in pediatric bone marrow donors.

We evaluated the use of a semi-automated processing technique to salvage red blood cells from pediatric bone marrow donors to minimize the risk of severe anemia following bone marrow harvest and ABO incompatibility in the recipient. Sixty healthy, HLA-matched, pediatric donors of bone marrow hematopoietic cells with a median age 8.0 years (2-19) were studied. Thirteen of the donor-recipient pairs were ABO incompatible. There were 60 recipients with a median age of 8.6 years (2 months to 20.8 years). Bone marrow was harvested under general anesthesia, filtered in the operating room and then transferred to the stem cell laboratory for processing. Samples were obtained for cell count, CD34+ quantification, colony assay, viability, and bacteriologic cultures before and after processing. The cells were processed in a semi-automated closed system (Stericel, Terumo) by density gradient separation with Ficoll-Hypaque and then washed. Two aliquots were obtained: one containing the mononuclear cell layer to be infused to the recipient and the other the washed red cells to be infused to the donor. The median volume harvested was 608 +/- 40.42 ml (278-1409), while the final volume infused was 174 +/- 10.75 ml (30.2-380) P < 0.0001, representing a decrease of 72% of the volume infused. The nucleated cell count harvested was 1.6 x 10(10) +/- 0.1 (0.56-3.2), while the count infused was 6.9 x 10(9) +/- 0.1 (0.12-5.4) P < 0.0001. The median mononuclear cell count (MNC) per kg harvested was 0.67 x 10(8) +/- 0.05 (0.18-2.0) vs an infused cell number of 1.3 x 10(8) MNC/kg +/- 0.1 (0.6-33.6) P < 0. 0001. The CD34+ cells harvested were 2.8 x 10(6)/kg +/- 0.1 (0.25-10.2) vs an infused number of 6.0 x 10(6)/kg +/- 0.5 (0.84-31.0) P < 0.0001. The viability before and after processing was 99%. Red cell salvage performed in a semi-automated closed system is safe and reduces the risk of post-bone marrow harvest anemia in pediatric donors, decreases the volume infused into the donor and enriches the mononuclear and CD34+ cell population, without affecting hematopoietic reconstitution.

Adolescent↗
PubMed1999

Two-day collection and pooling of peripheral blood stem cells with semiautomated density gradient cell separation.

Autologous and allogeneic PBSC collection and cryopreservation have been shown to be feasible in the pediatric population. This technique may be associated with complications, including volume overload and DMSO toxicity. To decrease these risks, we developed a technique by which PBSC are collected over a 2-day period and pooled prior to cryopreservation. PBSC are harvested on day 1 and stored with tissue culture medium on a rocker at ambient temperature. On day 2, a second PBSC harvest is performed, and the two harvests are pooled, separated on a Ficoll gradient in a semiautomatic closed system, and frozen with 10% DMSO after a soft spin for volume reduction. Cells from each day's harvest are tested for cell count and viability. A total of 36 collections in 26 patients were performed. This technique resulted in a 73%+/-0.0% reduction in volume (mean +/- SEM) and an 88%+/-0.9% depletion of RBC. Mononuclear cell (MNC) count recovery was 88%+/-2.6%, and the MNC dose delivered to the patient was 3.1+/-0.6x10(8) cells/kg. Cell viability was >98% before and after processing. Seventeen patients have been transplanted thus far, and all these patients engrafted with minimal toxicity. These data indicate that storing PBSC for up to 24 h after harvest does not decrease PBSC viability or delay engraftment.

Automation↗
PubMed1998

Outpatient total body irradiation prior to bone marrow transplantation in pediatric patients: a feasibility analysis.

Outpatient total body irradiation (TBI) prior to bone marrow transplantation has been accomplished in a total of 68 pediatric patients. The TBI regimen was fractionated with a total dose of 12 Gy in eight fractions twice daily. Antiemetic therapy consisted of oral ondansetron three times daily throughout the TBI course. Eight patients experienced mild nausea without vomiting, and four patients experienced mild nausea and vomiting. One patient required intravenous hydration after severe nausea and vomiting. Another patient experienced intractable diarrhea and dehydration which required inpatient management. Outpatient TBI prior to bone marrow transplantation is feasible in pediatric patients.

Adolescent↗
PubMed1998

Correction of neutropenia and hypogammaglobulinemia in X-linked hyper-IgM syndrome by allogeneic bone marrow transplantation.

X-linked hyper-IgM (X-HIM) syndrome is a primary immunodeficiency disease characterized by defects in both cellular and humoral immunity. X-HIM is caused by mutations in the gene for CD40 ligand (CD40L), a T cell membrane protein that mediates T cell-dependent immune functions. We report the case of a 6-year-old male with X-HIM due to an intronic mutation resulting in aberrant CD40L RNA splicing and absence of detectable CD40L protein. The patient had a history of multiple infectious complications and chronic neutropenia requiring treatment with recombinant granulocyte colony-stimulating factor, and underwent allogeneic bone marrow transplantation from an HLA-matched sibling donor. Following successful engraftment, T cell CD40L expression and immunoglobulin isotype switching were reconstituted and neutropenia resolved. Allogeneic bone marrow transplantation can correct neutropenia and reconstitute immune function in X-HIM.

Agammaglobulinemia↗
PubMed1998

Efficacy of autologous peripheral blood stem cell (PBSC) harvest and engraftment after ablative chemotherapy in pediatric patients.

Thirty-five pediatric patients, 1-16 years of age (median 6.3 years), with neoplastic solid tumors (n=32) or acute leukemia (n=3) underwent peripheral blood stem cell (PBSC) harvest and transplantation at Children's Memorial Hospital between September 1992 and April 1997. A median of four phereses were performed on each patient. Blood samples from 34 of the 35 patients were harvested through existing double-lumen central catheters, using either a Fenwal CS-3000 or COBE Spectra pheresis machine. The pheresis procedures were well tolerated overall. A median of 3.7 x 10(6)/kg CD34+ cells were infused (range, 0.2-15.5 x 10(6)/kg), and all patients engrafted. The median time to an absolute neutrophil count >500/microL was 13 days (range, 9-44 days) and to a platelet count >20,000/microL was 21 days (range, 9-210 days). Two patients died from transplant-related complications. Patients were discharged from the hospital after a median of 22 days (range, 15-64 days). Twenty of the 35 patients are alive, 17 of whom remain disease-free with a median follow-up of 1144 days. According to this study, PBSCs can be successfully harvested and re-infused for marrow reconstitution after myeloablative therapy in children for a variety of pediatric malignancies with low morbidity and mortality.

Acute Disease↗
PubMed1998

Peripheral blood stem cell transplantation in young children: experience with harvesting, mobilization and engraftment.

The purpose of this study was to determine the feasibility and assess optimal timing of harvesting peripheral blood stem cells (PBSC) for transplantation in young children. Thirteen children with body weight less than 25 kg, mean age of 3.9 years (1-9 yrs) who had recurrent solid tumors and leukemia were given tumor specific chemotherapy followed by i.v. rhG-CSF (5 microg/kg/d) for stem cell mobilization. Cytaphereses were done through a central venous line (CVL) during the marrow recovery phase (WBC >0.5 x 10(9)/l). The phereses were analyzed separately and assigned to three groups depending on the WBC at the time of the pheresis: Group I (WBC <1.0 x 10(9)/l), Group II [WBC in the range 1.0-3.0 x 10(9)/l] and Group III (WBC >3.0 x 10(9)/l). Samples from each harvest were assayed for cell count, CFU-GM, BFU-E, CD34+ cell count, and tumor cell immunocytology in patients with neuroblastoma (NBL). A median of 3.2 x 10(8) mononuclear cells per kg (MNC/kg), [mean 2.8 x 10(8) MNC/kg, standard error of the mean (SEM) +/- 0.74 (1.1-4.7)] were infused following myeloablative therapy. 78 phereses were performed in 13 children with a median weight of 18 kg (10-25 kg). A median of 5 phereses were performed per patient. There were no significant differences in the percentage and number of CD34+ cells, CFU-GM or BFU-E colonies assayed by plating 0.5 x 10(5) cells. Differences could be found in the total number of MNC (p<0.008) and the number of MNC/kg (p<0.001) between Groups II and III. No tumor cell contamination was detected in the NBL patients by immunocytology. All patients were rescued with PBSC and achieved sustained white cell engraftment (ANC >0.5 x 10(9)/l) at a median of 13.5 d (10-25 d) and platelet engraftment (untransfused platelet count >20.0 x 10(9)/l) at a median of 29 d (12-63 d). The only toxicity encountered during the phereses was thrombocytopenia in 4 patients whose median post-pheresis platelet count was 6.0 x 10(9)/l (3.0-9.01). It is concluded that collection of PBSC in young children is feasible and safe and can be performed through a cuffed CVL at the time of WBC recovery post mobilization with chemotherapy and G-CSF. Cytopheresis can be effectively performed when the peripheral WBC count approaches 1.0 x 10(9)/l. Following stem cell infusion, engraftment was prompt and durable.

Adolescent↗
PubMed1997

Prior fungal infection is not a contraindication to bone marrow transplant in patients with acute leukemia.

PURPOSE: Our aim was to assess the feasibility of bone marrow transplantation (BMT) in patients with acute leukemia who have had prior documented invasive fungal infection within 5 months pretransplant treated aggressively with systemic amphoteric in B and, when applicable, surgical resection of the infected tissue. MATERIALS AND METHODS: We reviewed the charts of patients with acute leukemia at our institution who underwent BMT between August 1992 and April 1994 after being treated for a severe fungal infection. We evaluated criteria for diagnosis of fungal infection, timing of infection in relation to BMT, and antifungal treatment modalities. We determined peritransplant complications, evidence for recurrence of fungal infection during BMT, morbidity related to antifungal drug therapy, and overall outcome in each patient. RESULTS: Fungal infection developed in eight patients. Sites of involvement included lung, liver, spleen, and skin. All patients were treated with systemic amphotericin B. Some also underwent surgical resection of infected tissue following clinical control of infection. All patients underwent BMT. Seven of eight patients engrafted and survived BMT. One patient died of recurrent pulmonary mucormycosis. Three patients are alive and free of leukemia and fungal disease. Four patients died of noninfectious causes and had no evidence of fungal disease at the time of death. CONCLUSIONS: Aggressive therapy of prior fungal infection followed by ongoing anti-fungal prophylaxis in acute leukemia patients may allow BMT without reactivation of the fungus. Reports of larger series of such patients as well as studies of the efficacy of chemoprophylaxis of fungal infections are needed.

Adolescent↗
PubMed1997

Haploidentical related umbilical cord blood stem cell transplant in a child with acute non-lymphocytic leukemia.

Umbilical cord blood stem cells (UCBSC) were used to reconstitute hematopoiesis following myeloablative therapy in a 13-month-old infant with acute nonlymphocytic leukemia (ANLL):FAB-M5 who had failed to sustain a chemotherapeutic remission. The patient's mother was 18 weeks pregnant with her second child at the time of diagnosis. Amniocentesis revealed that the fetus was HLA-haploidentical with the patient at the paternally inherited allele. The umbilical cord blood was harvested and processed by Ficoll centrifugation with 100% recovery of 5 x 10(7) mononuclear cells/kg and then cryopreserved. Two weeks after collection the cells were thawed and then infused into the patient following conditioning with total body irradiation, cyclophosphamide, and etoposide. Graft-versus-host-disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. The patient experienced clinical grade I GVHD consisting of skin involvement only that resolved within 2 weeks following the addition of corticosteroids. Engraftment was achieved with an absolute neutrophil count (ANC) above 0.5 x 10(9)/l on day 16, a platelet count above 50 x 10(9)/l on day 56, platelet transfusion independence on day 32 and red blood cell transfusion independence after day 44. Three months following transplantation restriction fragment length polymorphism (RFLP) revealed no discernible difference between the donor and the recipient. The patient remains in remission without evidence of GVHD 23 months post-transplant.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Treatment of poor-risk neuroblastoma patients with high-dose chemotherapy and autologous peripheral stem cell rescue.

A single institutional pilot study was conducted in which 12 poor-risk neuroblastoma (NB) patients were uniformly treated with multi-agent induction chemotherapy followed by myeloablative consolidation chemotherapy and unpurged peripheral blood stem cell (PBSC) rescue. In addition to using standard criteria for evaluating response to induction chemotherapy, tumor cell contamination of the peripheral blood and/or bone marrow was analyzed in seven patients by immunocytology using a panel of five anti-NB monoclonal antibodies. Seven patients had morphologic evidence of bone marrow disease at the time of diagnosis, and two additional patients had tumor cells detected in bone marrow samples by immunocytology prior to the second cycle of chemotherapy. After three cycles of chemotherapy, two of the 12 patients continued to have evidence of bone marrow disease. Samples from 29 PBSC harvests collected from nine patients were also analyzed for the presence of contaminating tumor cells by immunocytology. In each case, the stem cells were found to be free of tumor. Eleven of the 12 patients underwent myeloablative therapy and PBSC rescue; five patients remain alive without disease progression, 28+ to 53+ months from diagnosis, and six patients have developed recurrent disease. We conclude that PBSCs can be successfully harvested from children with NB, and used for hematopoietic reconstitution following myeloablative chemotherapy. However, more effective therapy for poor-risk NB patients is still urgently needed.

Adult↗