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H van der Lelie

Publications and source records attributed to H van der Lelie.

At least 19 recordsLinked to original sources
PubMed2004

SBDS mutations and isochromosome 7q in a patient with Shwachman-Diamond syndrome: no predisposition to malignant transformation?

Shwachman-Diamond syndrome (SDS) is a genetic disorder characterized by pancreatic hypoplasia, recurrent infection, and bone marrow (BM) dysfunction. SDS-patients have an increased frequency of myelodysplasia and leukemic transformation. Unspecific cytogenetic aberrations are a common finding in SDS. However, in a rising number of patients abnormalities of chromosome 7 have been reported, especially an i(7)(q10), which seems to be a non-random chromosome abnormality. Recently, the SDS gene has been mapped at locus 7q11 and subsequently cloned; recurrent mutations have been found. We report a case of SDS with an i(7)(q10) in the BM and two different mutations in the SBDS gene. At the age of 25 years, the patient suffers from mild aplastic anemia but does not show any clinical sign of myelodysplasia or leukemic transformation.

Adult↗
PubMed2001

In vitro migratory capacity of CD34+ cells is related to hematopoietic recovery after autologous stem cell transplantation.

To investigate whether the migratory ability of peripheral blood-derived CD34+ cells of patients undergoing autologous peripheral blood stem cell transplantation is related to the homing efficiency of these cells, the migration in vitro of these cells was determined and correlated with in vivo hematopoietic recovery. Large inter-individual differences of the in vitro migratory ability of the CD34+ cells were observed, ranging from 1.1% to 16.4% for spontaneous migration and 6.2% to 40.8% for SDF-1-induced (100 ng/mL) migration. Significantly faster hematologic recovery was observed in those patients who received transplanted CD34+ cells that showed high spontaneous and SDF-1-induced migration in vitro (P <.05). Moreover, CD34+ cells from healthy G-CSF-mobilized donors exhibited significantly higher spontaneous and SDF-1-induced (P <.01) migration than CD34+ cells from patients mobilized with chemotherapy and G-CSF. The lower migratory capacity in vitro of patient-derived CD34+ cells was not due to lower expression of CXCR-4 but probably reflected decreased motogenic behavior of the cells. These results indicate that the migratory capacity of the cells is important for hematopoietic recovery. The data suggest that the engraftment potential of autologous stem cells is more or less impaired by treatment before or during the mobilization procedure and might possibly be restored by in vitro manipulation of the cells. In addition, an exponential relation between CXCR-4 expression and number of CD34+ cells that mobilized to the peripheral blood was found (P <.001), suggesting that CXCR-4 expression plays a role in the mobilization of CD34+ cells.

Adolescent↗
PubMed2001

Effect of locally applied GM-CSF on oral mucositis after stem cell transplantation: a prospective placebo-controlled double-blind study.

Oral mucositis is a frequent side effect of myeloablative chemo- and radiotherapy preceding stem cell transplantation. It causes pain, poor food intake, and is a port of entry for infection. We studied whether GM-CSF applied topically in the oral cavity can prevent or ameliorate this mucositis. In 36 consecutive patients undergoing a stem cell transplantation, we performed a double-blind placebo-controlled study of 300 micrograms GM-CSF in a 2% methylcellulose gel daily versus a 2% methylcellulose gel alone. Both were locally applied in the oral cavity. The primary end-point was mucositis as measured by the WHO toxicity scale for mucositis, oral assessment scale, and a subjective pain scale, all scored daily. The secondary end-points were need to give parenteral nutrition and morphine, incidence of fever and infections, and duration of neutropenia and hospitalization. No differences were found in the median subjective pain scores, WHO scores, and oral assessment scores between the placebo and the GM-CSF groups. In both groups, nine patients required morphine for pain control. Ten patients in the placebo group and 11 in the GM-CSF group received parenteral nutrition. Documented infections, use of broad-spectrum antibiotics, and number of days with fever were similar in the placebo and the GM-CSF groups. The duration of neutropenia below 0.5 x 10(9)/l (median 14.5 days in the placebo group versus 17 days in the GM-CSF group) and the duration of hospitalization (28.5 versus 29 days) was also not significantly different. We found no beneficial effect of 300 micrograms GM-CSF dissolved in a 2% methylcellulose gel applied locally for chemo- and radiotherapy-induced mucositis in patients undergoing a stem cell transplantation.

Administration, Topical↗
PubMed1999

The depletion of T cells from haematopoietic stem cell transplants.

OBJECTIVE: In our laboratory, we have developed an immunorosette technique for the depletion of T cells from bone marrow transplants. Tetrameric complexes of monoclonal antibodies are able to form very stable immunorosettes, which are efficiently depleted with the aid of a blood cell separator. Major improvements over the original sheep red blood cell depletion are the use of human (patient or donor derived) erythrocytes instead of sheep-derived cells, and the possibility of using a closed system for separation in a cell separator. In contrast to bone marrow, mobilized haematopoietic stem cell transplants obtained after leucocytapheresis contain higher numbers of T cells. Therefore, a different approach is necessary. METHOD: We have used two CD34 selection systems (Isolex 300SA and the Clinimacs) to perform T-cell depletions from peripheral blood stem cell (PBSC) transplants. RESULTS: Immunorosette T-cell depletion, with CD2/CD3 tetrameric complexes, of bone marrow transplants resulted in a mean 2.5 log depletion of T cells with a yield of 50% of the CD34+ cell population. Stem cell selection of PBSC transplants using one of the CD34 selection procedures resulted in a 4.5 log depiction of T cells for both systems, but with different results for the recovery of CD34+ cells. An increased yield of CD34+ cells was obtained with the Clinimacs procedure (57.9+/-9.0%) in comparison to the Isolex procedure (40.1+/-12.5%). CONCLUSION: Our own immunorosette depletion technique and the two tested CD34 selection methods for stem cell transplants both resulted in a very efficient T-cell depletion with the recovery of 40-60% of the CD34 haematopoietic stem cells present in the transplant.

Antigens, CD34↗
PubMed1998

Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections.

It has been suggested that a better outcome of neutropenia-associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used. We now report a randomized multicentre study comparing liposomal amphotericin B (AmBisome, 5 mg/kg/d) to amphotericin B deoxycholate (AmB, 1 mg/kg/d) in the treatment of these infections. Of 106 possible patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group (n = 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients (n = 34) treated with AmB (P=0.09); P=0.03 for complete responders. A favourable trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis (P=0.05 and P=0.096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P=0.03). More patients on AmB had a >100% increase of their baseline serum creatinine (P<0.001). The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.

Adult↗
PubMed1995

Hemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support.

BACKGROUND: Chemotherapy intensification may lead to new forms of toxicity such as hemolytic uremic syndrome. METHODS: Three patients are described who developed this complication 4 to 6 months after high dose chemotherapy followed by autologous stem cell support. The literature on this subject is reviewed. RESULTS: One patient was conditioned with BEAC (carmustine, etoposide, cytosine arabinoside, and cyclophosphamide) and received autologous bone marrow. The other two underwent triple peripheral stem cell transplantation after conditioning with CTC (carboplatin, cyclophosphamide, and thiotepa). Symptoms were hypertension, microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency. One patient had a retinal vein thrombosis. One patient died of a cardiac arrest shortly after the diagnosis was made. The remaining two achieved a partial remission: one with fresh frozen plasma without plasmapheresis and fresh frozen plasma, but improved on high dose intravenous immunoglobulin and vincristine. CONCLUSIONS: Hemolytic uremic syndrome is a serious complication of the more intensive chemotherapy made possible by stem cell support. Because of the rapidly growing indications for this approach, an increase in this type of vascular complication is expected.

Adult↗
PubMed1995

Microscopic haematuria as a relative contraindication for tranexamic acid.

Tranexamic acid has been advocated for patients with severe bleeding tendency due to thrombocytopenia not responding to platelet transfusions. Macroscopic haematuria is a well-known contraindication for its use in such patients. We present three clinical cases with microscopic haematuria, in whom tranexamic acid caused problems of clot formation in the urinary tract, indicating that microscopic haematuria should also be considered as a contraindication for tranexamic acid.

Adult↗
PubMed1995

Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy.

PURPOSE AND METHODS: A prospective, randomized, multicenter phase III trial was performed to investigate the feasibility of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in elderly patients ( > or = 60 years) with advanced non-Hodgkin's lymphoma (NHL) of intermediate- and high-grade malignancy, and to compare the tolerance and efficacy of doxorubicin versus mitoxantrone (CHOP v CNOP). RESULTS: Of 157 enrolled patients, 148 were eligible and 145 were assessable for response. Thirty-one percent of CNOP and 45% of CHOP patients completed six cycles without dose reduction. The cumulative normalized dose-intensity (NDI) was 92% with CHOP and 90% with CNOP after six cycles. The overall complete response (CR) rates were 49% and 31% in CHOP- and CNOP-treated patients, respectively (P = .03). Survival with CNOP was significantly worse as compared with CHOP (P = .03). Lymphoma-specific survival was significantly better in CHOP-treated patients (P = .034) At 3 years, 42% of CHOP and 26% of CNOP patients were alive. Additional unfavorable prognostic factors at diagnosis were high serum lactate dehydrogenase (LDH) level, bulky mass, and low performance status, but not age. The median disease-free intervals of complete responders were 27 (CHOP) and 15 (CNOP) months, respectively. Considering the complete group of patients, at 3 years 17% of CHOP and 13% of CNOP patients were alive and disease-free (P = .12). Common toxicity criteria (CTC) grade > or = 2 with CNOP and CHOP was not different. CONCLUSION: CHOP is well tolerated in elderly patients with advanced intermediate- or high-grade NHL and its NDI is not seriously impaired. Treatment with CHOP (doxorubicin) results in better CR and survival rates than CNOP (mitoxantrone). CHOP should be recommended for elderly patients with high-risk NHL.

Aged↗
PubMed1995

Fusobacterium nucleatum, a new invasive pathogen in neutropenic patients?

Three chemotherapy-induced neutropenic hematologic patients with severe systemic infection caused by Fusobacterium nucleatum, a Gram-negative anaerobic rod, are described. Anaerobic infections are not very common in this patient category, but in a short period of time, several such patients were seen. The infection was considered to be caused by a combination of chemotherapy-induced mucositis, which served as a portal of entry for the systemic infection, and the antibiotic regime used in these patients. This is a serious infection with a high mortality. In hematological neutropenic patients suffering from severe mucositis and fever, antibiotic therapy should cover anaerobic bacteria.

Adult↗
PubMed1995

Corynebacterium CDC group JK (Corynebacterium jeikeium) sepsis in haematological patients: a report of three cases and a systematic literature review.

We describe 3 patients with Corynebacterium jeikeium sepsis in neutropenic phase during treatment for acute myeloid leukaemia. Fever was the first symptom. All had a central venous catheter which was removed. Two patients developed subcutaneous nodules containing pus when the neutrophil count recovered; 1 had intracutaneous and pulmonary lesions. They were treated with vancomycin and recovered when the neutrophil count started to rise. A review of 80 neutropenic patients with C. jeikeium sepsis reported in the literature, together with our 3 cases indicates that risk factors for infection are the presence of a central venous catheter, being an adult male or postmenopausal female, profound and prolonged neutropenia and exposure to multiple antibiotics. Skin lesions are reported in 48% and pulmonary lesions in 36% of the patients. The overall mortality is 34% but in patients with recovery of the bone marrow only 5%. Therefore haematopoietic growth factors should be considered in neutropenic patients with C. jeikeium infection.

Adult↗
PubMed1994

Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity.

BACKGROUND: Glutamine-supplemented total parenteral nutrition (TPN) improved the nitrogen balance in catabolic situations. In animal studies, parenteral glutamine supplementation appeared to maintain gut integrity. This study was performed to evaluate the possible positive effects of glutamine supplementation in catabolic hematologic patients. METHODS: This was a prospective double-blind placebo-controlled pilot study, in which 20 treatment cycles in unselected hematologic patients with intensive chemotherapy were studied. Glutamine was given as a dipeptide. Patients were randomized per treatment cycle to receive isonitrogenous TPN (0.272 g nitrogen/kg of body weight) and isoenergetic TPN (2200 kcal NPE/day) without or with 40 g L-alanyl-L-glutamine (26 g glutamine) until the neutrophil count was greater than 0.5 x 10(9)/L. The daily oral food intake was recorded and analyzed carefully. Toxicity grades for performance status, mucositis, and diarrhea were scored according to the World Health Organization classification. RESULTS: No differences in neutropenic period, fever, extra antibiotics, and toxicity scores were observed, except for a gain in body weight per treatment cycle in favor of the glutamine-supplemented TPN. No side effects or allergic reactions were noted after the dipeptide administration. CONCLUSION: Supplementation of glutamine dipeptide was safe but had no significant positive clinical effect.

Adult↗
PubMed1994

Pregnancy and paroxysmal nocturnal hemoglobinuria.

A patient is described who developed symptoms of paroxysmal nocturnal hemoglobinuria (PNH) in her first pregnancy. This was uneventful except for a spontaneous preterm delivery. The second pregnancy was complicated by severe anemia and a hemolytic crisis with Budd-Chiari syndrome at 31 weeks' amenorrhoea. Delivery was again preterm and was the result of induced labour after premature rupture of membranes at 34 weeks. Literature shows a high maternal mortality among PNH patients (5.8%). The most common cause of death is liver vein thrombosis (Budd-Chiari syndrome). Fetal wastage (30%) and prematurity rate (16%) are also high. Recommendations for follow-up and therapy are given such as anticoagulation therapy, platelets and washed erythocytes transfusions, screening for Budd-Chiari syndrome and infections.

Adult↗
PubMed1994

Intrahepatic cholestasis and biliary cirrhosis associated with extrahepatic Hodgkin's disease.

A 29-year-old male with supraclavicular Hodgkin's disease (Stage IA) developed intrahepatic cholestasis. Cholestasis with severe pruritus persisted while the Hodgkin's disease was brought into remission by radiotherapy. During ursodeoxycholic acid treatment jaundice and hypercholesterolaemia decreased and pruritus disappeared. However, 2 years after diagnosis the patient died of variceal haemorrhage. On autopsy no recurrence of Hodgkin's disease was found. The liver showed advanced biliary cirrhosis. Intrahepatic cholestasis in this patient persisted as a paraneoplastic phenomenon despite complete remission of Hodgkin's disease.

Adult↗
PubMed1993

The value of surveillance cultures in neutropenic patients receiving selective intestinal decontamination.

230 neutropenic episodes in 84 patients with acute myeloid leukemia receiving selective intestinal decontamination were studied to evaluate the ability of surveillance cultures to monitor the efficacy of microbial suppression, to identify causative organisms in case of fever, and to predict infection due to potential pathogens (i.e. Staphylococcus aureus and aerobic Gram-negative bacteria). Most cultures became negative soon after the administration of prophylactic antibiotics and there were only few persistent colonizations. 14 potential pathogens resistant to the intestinal decontamination regimen were isolated in surveillance cultures, none of which caused infection. Of the 212 febrile episodes, only 22 were caused by a microbiologically documented infection with potential pathogens. Most microbiologically documented infections were caused by organisms not routinely identified by surveillance cultures, indicating efficient selective intestinal decontamination. Only 9 (41%) of the 22 infections with potential pathogens were predicted by surveillance cultures. We conclude that surveillance cultures are of limited use in predicting infection or identifying causative organisms of fever in neutropenic patients receiving selective intestinal decontamination. However, they are useful in monitoring the efficacy of microbial suppression. One set of surveillance cultures each week after the disappearance of potential pathogens would be sufficient.

Adult↗
PubMed1991

Incidence and clinical epidemiology of streptococcal septicemia during treatment of acute myeloid leukemia.

The incidence and outcome of streptococcal septicemia was analyzed in 76 consecutive patients with newly diagnosed and relapsed acute myeloid leukemia. They received 215 courses of remission induction or intensive consolidation treatment. There were 31 different episodes of streptococcal septicemia in 27 patients, making these microorganisms the most frequently encountered bacteria in blood cultures. This high incidence coincided with the introduction of selective intestinal decontamination. In 24 episodes (20 patients) there was a fast recovery, but 7 patients developed pulmonary symptoms resulting in death due to respiratory failure in 5 of them. The infections all occurred in the phase of maximum bone marrow suppression 1-3 weeks after the start of the chemotherapy. Streptococcal septicemia was not limited to patients treated with cytosine arabinoside but also occurred in patients treated with other regimens of intensive chemotherapy. In 28 episodes there were no focal signs of infection, but in half there were symptoms of treatment induced gastrointestinal toxicity. The streptococci probably invade through oral and gastrointestinal mucosa damaged by the chemotherapy. Selective decontamination may play a promoting role.

Adult↗
PubMed1990

Fatal mucormycosis presenting as an appendiceal mass with metastatic spread to the liver during chemotherapy-induced granulocytopenia.

Opportunistic fungal infections occur with increasing frequency during chemotherapy induced granulocytopenia. A 27-year-old woman developed mucormycosis in the ileocecal region with fatal dissemination to the liver while receiving consolidation therapy for acute T-lymphoblastic leukemia. The infection occurred during a period of decreased colonization resistance in the intestinal tract. Early symptoms were high fever unresponsive to broad spectrum antibiotics, severe pain in the right lower abdominal quadrant and diarrhoea. This was followed by an infiltrate in the right abdomen, ileus, and icterus. Diagnosis was established in the living patient by thin needle aspiration from affected liver tissue. Giemsa's stain and fungal cultures revealed Mucor indicus. The fatal outcome of disseminated mucormycosis justifies a high index of suspicion and a maximal (invasive) diagnostic effort as localised infections might be cured by resection and amphotericin B.

Adult↗
PubMed1989

Therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea.

Treatment of the myeloid blast phase of chronic granulocytic leukemia is still a major problem in clinical hematology. Alternate-day plicamycin and hydroxyurea treatment was reported to induce remissions in the majority of patients with myeloid blast phase by Koller and Miller in 1986 Subsequently we treated eight patients according to this regimen. Complete remissions could not be achieved and no prolongation of median survival was observed. In two patients treatment had to be discontinued due to severe toxicity.

Adult↗