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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Shwachman-Diamond syndrome (SDS) is a rare inherited disorder involving concomitant neutropenia and exocrine pancreatic insufficiency. About 25% of patients develop hematopoietic malignancies. We describe a 24-year-old male patient with SDS who underwent allogeneic bone marrow transplantation (BMT) because of progression into acute myeloid leukemia (AML) following myelodysplastic syndrome (MDS). The BMT preparative regimen consisted of busulfan (16 mg/kg body wt.), followed by cyclophosphamide (120 mg/kg). Cyclosporin A and short methotrexate were used for graft-versus-host disease (GvHD) prophylaxis. The post-transplant period was complicated by staphylococcal septicemia, CMV infection, renal insufficiency, and acute GvHD grade III. Hematological recovery was delayed (post-transplant day +55). The patient was discharged at day +68 in complete remission without any evidence of MDS. RFLP fingerprint analysis showed complete engraftment of the donor's hematopoiesis. The patient's leukemia relapsed 9 months post-transplant, and death followed due to CMV infection and multiorgan failure. Despite the fatal course in this patient, allogeneic BMT could be an option for curative treatment of the hematopoietic failure in SDS. The interaction of BMT with pancreatic insufficiency still has to be ascertained.
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PMID:Allogeneic bone marrow transplatation in a patient with Shwachman-Diamond syndrome. 859 12

Bacterial complications develop mainly after transplantation during the period before engraftment takes place. Wound infections, urinary tract infection and pneumonia are the commonest complications of solid organ transplantation and generally involve Gram-negative bacilli and Staphylococcus aureus. However, Gram-positive cocci will predominate when selective oral antimicrobial prophylaxis is given as is frequently the case in bone marrow transplant recipients. Oromucositis, induced by total body irradiation or anthracyclines, result in more bacteraemia due to oral viridans streptococci. The use of central intravenous catheters leads to an increase in bacteraemia and infection due to coagulase-negative staphylococci. Patients requiring intensive care are also at risk of nosocomial infections including legionellosis. Once engraftment has occurred, there is much less risk of bacterial infection but patients remain vulnerable to the intracellular pathogens Listeria monocytogenes, non-typhoid salmonellae, Norcardia spp. and mycobacteria for as long as they require immunosuppression. Any rejection crisis must be treated aggressively with high-dose steroids or other agents which further undermine an already fragile immunity. In bone marrow transplant recipients, graft versus host disease and its treatment exerts a more profound effect on immunity and often coincides with cytomegalovirus infection which compromises the patient even further. Such patients are again at risk of infection with the same range of pathogens encountered during neutropenia since the oral mucosa, gut and catheter, if one is present, provide the same portals of entry. Immunosuppressive therapy, in some centres, is discontinued once the risk of graft versus host disease is reduced, although the reconstitution of the immune system is a lengthy process and there is a continued deficiency of IgG which renders patients unable to opsonise the encapsulated bacteria Streptococcus pneumonia and Haemophilus influenzae. In contrast to bone marrow transplant recipients, those with a solid organ transplant require life-long immunosuppression and so remain susceptible to infections with intracellular pathogens and, even with minimal immunosuppression, there will always be the risk that common bacteria will cause infection in unusual places and that uncommon organisms will be involved in apparently straightforward infections.
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PMID:Bacterial complications of transplantation: diagnosis and treatment. 860 44

Over the past ten years, the availability of pharmacologic quantities of hematopoietic growth factors has opened many avenues of study in basic science and clinical investigation. Numerous studies performed to date have demonstrated significant benefits from the use of these cytokines. The side effect profiles, particularly for "later acting" growth factors, indicate that they are generally well tolerated by most patients. The table summarizes the potential indications for hematopoietic growth factor use as discussed in this article, as justified by current evidence of benefit, harm, and cost effectiveness resulting from their use in various clinical settings. It has been clearly demonstrated in standard-dose chemotherapy regimens that these agents shorten the duration of myelosuppression, reduce the incidence of significant infection, can shorten hospital stay, and reduce antibiotic use for most patients, although the cost/benefit ratio for growth factors such as G-CSF makes this a cost-effective approach only for regimens with a high (40 percent or more) incidence of febrile neutropenia. Limited indirect evidence supports the use of growth factors in patients with a prior episode of fever and neutropenia. The suppressive approach to growth factor use could potentially benefit patients with documented infection or clinical deterioration, but it has not otherwise been shown to be a particularly effective or cost-effective approach. Administration of hematopoietic growth factors has been instrumental in facilitating both autologous and allogeneic peripheral progenitor cell mobilization and techniques such as ex vivo expansion. There is an increasing body of data supporting the use of high-dose chemotherapy regimens with progenitor cell rescue for a number of malignancies and limited data supporting the benefits of maintaining dose-intensity for certain malignancies in standard-dose settings. Although of continuing concern, clinically significant evidence of disease stimulation and recurrence has not been unequivocally demonstrated in studies to date. A comprehensive set of evidence-based guidelines has recently been published by the American Society of Clinical Oncology. As often is the case, current studies have perhaps generated more questions than answers. Future investigation will undoubtedly focus on use of hematopoietic growth factors in conjunction with other techniques, such as outpatient-based treatment of febrile neutropenia, CD34-positive stem cell selection in autologous transplantation, selective manipulation of T-cell subsets (to decrease the incidence of severe graft-versus-host disease) in allogeneic transplantation, and high-dose therapy with stem cell transplantation.
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PMID:Hematopoietic growth factors. 864 43

The role of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in myeloid recovery of children given an allogeneic bone marrow transplant (BMT) from an HLA-identical sibling for acute leukemia was evaluated in a retrospectively historically controlled study, involving 20 consecutive treated patients and 30 historical controls. In order to investigate the efficacy of rHuG-CSF in patients given a matched unrelated BMT with methotrexate as part of graft-versus-host disease (GVHD) prophylaxis, we also analyzed the kinetics of engraftment in eight further children with acute or chronic leukemia, transplanted using a volunteer donor. Patients were treated with 5 micrograms/kg/day of rHuG-CSF by 1-h intravenous infusion from day +5 until the absolute neutrophil count (ANC) was > or = 2 x 10(9)/l. No adverse effect related to treatment was observed in any patients. Children transplanted from an HLA-identical sibling and treated with rHuG-CSF reached an ANC count greater than 0.5 x 10(9)/l, 1 x 10(9)/l and of 2 x 10(9)/l in a significantly shorter time than the control group (day +9, +10 and +12, vs day +15, +22 and +29, respectively). An accelerated granulocyte production was also observed in patients receiving an unrelated transplant after a GVHD prophylaxis schedule including methotrexate, the median time to neutrophil recovery above 0.5 x 10(9)/l, 1 x 10(9)/l and 2 x 10(9)/l being +14, +15 and +17 days, respectively. In comparison to historical controls, all rHuG-CSF-treated patients had fewer days of fever, of antibiotic therapy and, only for children with HLA-compatible siblings, of hospitalization, whereas in the three groups the duration and severity of mucositis were comparable. No difference between the rHuG-CSF-treated patients and the historical controls given BMT from HLA-identical sibling was seen with regard to incidence of acute or chronic GVHD, relapse rate and actuarial event-free survival at day +100 and 1 year after transplantation. Our data suggest that in children given allogeneic BMT for acute or chronic leukemia, rHuG-CSF reduces duration of neutropenia, without increasing the rate of relapse or the incidence and severity of GVHD.
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PMID:Use of recombinant human granulocyte colony-stimulating factor in children given allogeneic bone marrow transplantation for acute or chronic leukemia. 867 51

Cytopenias following bone marrow transplantation may be severe and life-threatening. These have been described post-allogeneic Klumpp, 1991: Bone Marrow Transplant 8:159-171. or post-autologous bone marrow transplants Khouri et al., 1994: J Clin Oncol 12:748-758. as well as with peripheral blood stem cell transplantation Klumpp et al., 1992: Am J Hematol 41:215-217. It can be immune mediated, associated on occasions with graft-versus-host disease (GVHD) Anasetti et al., 1989: Blood 4:1054-1058; however, in most cases, the underlying mechanism is uncertain. The treatment of post-transplant cytopenias is not well established, and they are often refractory to immunosuppressive therapy with steroids. Herein we describe two cases of neutropenia after allogeneic bone marrow transplantation that improved after therapy with high-dose intravenous immunoglobulin.
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PMID:Neutropenias following allogeneic bone marrow transplantation: response to therapy with high-dose intravenous immunoglobulin. 870 51

Hepatic dysfunction is common in patients who receive intensive chemotherapy and it is important to determine the etiology in order to institute appropriate therapy. The role of laparoscopic liver biopsy in patients with neutropenia, thrombocytopenia, or both was evaluated as a mean of making treatment decisions and as a determinant of clinical outcome. Laparoscopic liver biopsy was performed in 29 subjects who were receiving intensive cytotoxic therapy with or without bone marrow transplantation. One to three direct-vision laparoscopic liver biopsies were performed in each patient using a Tru-cut needle during general anesthesia. Platelet concentrate transfusions were usually given before, during, and immediately after biopsy. Bleeding was controlled with spatula electrocautery. Thirty-two biopsies were obtained in 29 patients. At the time of liver biopsy, white blood cell and platelet counts ranged from 0 to 14,300/microliters (median: 2500/microliters), and 1000 to 47,000/microliters (median: 20,000/microliters), respectively. Bleeding at the liver biopsy site was readily controlled during the procedure without clinical evidence of significant bleeding; no procedure-related complications were noted and no patients required re-exploration. All biopsies were informative and the lesions observed in 32 biopsies revealed graft-versus-host disease (n = 5), hepatic candidiasis (n =1), hepatic veno-occlusive disease (n = 3), cholestasis (n = 19), hemosiderosis (n = 26), toxic injury (n = 8), hepatic steatosis (n = 4), granuloma (n = 1), viral infection (n =1), and malignancy (n = 1). Laparoscopic liver biopsy has been proven to be an effective means of assessing the cause of liver dysfunction in patients who were thrombocytopenic and immunosuppressed. The diagnosis obtained at laparoscopic liver biopsy altered therapy in nine of 29 (31%) patients.
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PMID:Laparoscopic liver biopsy to evaluate hepatic dysfunction in patients with hematologic malignancies: a useful tool to effect changes in management. 872 71

Sixty-five patients with haematological malignancy received high-dose chemotherapy or chemoradiotherapy followed by a T replete, HLA-identical sibling bone marrow transplant. All were scheduled to receive a standard cyclosporine/methotrexate immune suppressive regimen to minimise the risk of graft-versus-host disease post-transplant. Forty-six patients received all four scheduled doses of methotrexate, while in nineteen the day 11 dose was omitted due to marked oropharyngeal mucositis or febrile neutropenia. There was a slight increase in the incidence of acute graft-versus-host disease (GVHD) grades I-IV in those not receiving compared to those receiving day 11 methotrexate (84 vs 71% (P = 0.04)). However, there was no difference in the incidence of acute GVHD grades II-IV (14 vs 22%), in the incidence of chronic GVHD (38 vs 47%), in transplant-related mortality (21 vs 24%), in relapse rate (42 vs 51%), in 4-year survival (38 vs 48%), or in disease-free survival (38 vs 42%). These findings suggest that the day 11 methotrexate dose could be omitted without a major deleterious effect on the outcome of HLA-identical sibling marrow transplantation.
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PMID:Omission of day 11 methotrexate does not appear to influence the incidence of moderate to severe acute graft-versus-host disease, chronic graft-versus-host disease, relapse rate or survival after HLA-identical sibling bone marrow transplantation. 875 Feb 65

An 8-year-old boy with combined IgG1 deficiency and neutropenia underwent allogeneic BMT from his HLA-identical, MLC-negative sister, because immunoglobulin (Ig) infusions and prophylactic antibiotics failed to prevent life-threatening infections. Conditioning was with busulfan and cyclophosphamide, MTX and CYA were given for the prophylaxis of GVHD. For 16 months after BMT no serious infections have occurred and serum IgG1 levels have returned to the normal range without Ig replacement. BMT may be appropriate treatment for patients with IgG subclass deficiency who rarely respond to conservative therapy.
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PMID:Successful bone marrow transplantation in a child with combined IgG subclass deficiency and neutropenia. 875 Feb 81

We report the first experience of the use of GM-CSF as prophylaxis of ganciclovir induced severe bone marrow suppression in a CMV seropositive patient with acute myeloid leukemia who underwent a complete remission after an allogeneic bone marrow transplantation from an identical HLA sibling who also was CMV seropositive. A successful bone marrow engraftment was documented by day 14. Once peripheral blood counts stabilized, the patient received ganciclovir 5 mg/kg TIW. By day 73 severe neutropenia was documented but a spontaneous improvement occurred with discontinuation of ganciclovir. From day 100 to day. 110 he received daily ganciclovir at a dose of 5 mg/kg and the same dose of GM-CSF without signs of toxicity. There was no evidence of either acute graft versus host disease or of CMV infection. One year after transplantation he relapsed and died of complications of acute leukemia.
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PMID:[Prevention of myelotoxicity in a case of bone marrow transplantation using granulocyte-macrophage colony-stimulating factor along with ganciclovir]. 881 88

We evaluated the toxicity and efficacy of high-dose etoposide, cyclophosphamide and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) for patients with resistant, acute myeloid leukemia (AML). Between 9/84 and 11/92 we treated 70 patients with etoposide (900-1800 mg/m2), cyclophosphamide (120-180 mg/kg) and TBI (1000-1200 cGy) followed by allogeneic BMT from histocompatible siblings. Forty patients were in untreated first relapse. Median time from diagnosis to transplant was 10 months. Toxicity was similar to that observed with cyclophosphamide/TBI with the median duration of neutropenia (ANC < 500/microliters) being 19 days (range 10-27) and the median duration of thrombocytopenia being 23 days (range 13-173). Twenty-three patients remain in continuous complete remission at a median of 56 months after transplant (range 36-132 months). Probabilities of disease-free survival, persistent/recurrent disease and transplant related mortality are .32, .47, and .37 respectively. Multivariate analysis indicated that grade > or = 2 acute graft-vs-host disease and transplant in untreated first relapse were associated with increased DFS due to reduced relapse risk. We conclude that high-dose etoposide with cyclophosphamide and TBI followed by allogeneic BMT is effective therapy for resistant AML, producing durable remission in approximately one-third of those treated. Disease persistence or recurrence was the major cause of treatment failure. Further improvement in DFS following allogeneic BMT for resistant AML might be achieved by using less intensive GVHD prophylaxis or through infusion of donor peripheral blood cells in patients who fail to develop significant acute GVHD.
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PMID:High-dose etoposide, cyclophosphamide and total body irradiation with allogeneic bone marrow transplantation for resistant acute myeloid leukemia: a study by the North American Marrow Transplant Group. 881 76


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