Granulocyte Transfusions Research Articles

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Aspergillus flavus sinusitis in ALL

A 17-year-old girl with ALL developed acute onset left eye swelling and facial pain on day 23 of phase II of the UKALL XII protocol. She had been neutropaenic for 14 days at this time. She had neutropenic fever since day 17 with no obvious cause for this identified up to the time facial swelling appeared. This occurred despite broad-spectrum antibiotic therapy and empiric liposomal amphotericin therapy for her neutropenic fever. The liposomal amphotericin had been commenced 3 days prior to symptoms developing at a dose of 3 mg/kg/day. The eye swelling progressed rapidly with increased pain and closure of left eye within 24 h. Imaging with MRI demonstrated left sided sinusitis (Image 1). The patient was taken to theatre for emergency washout. Findings at surgery demonstrated a soft tissue mass extending onto the skull base, posterior choana and encasing the middle turbinate (Image 2). Microscopy of scrapings from the infiltrate demonstrated an organism with septated hyphae and dichotomous branching (Image 3). Culture of this organism confirmed a diagnosis of Aspergillus flavus sinusitis. Post surgery, the patient continued to improve with high dose liposomal amphotericin (10 mg/kg/day) and caspofungin (50 mg daily). Her pyrexia settled within 36 hr of surgery. She returned to theatre 1 week later for a further washout and at this stage a marked improvement was noted. Neutrophil recovery did not occur until 22-days post initial surgical intervention. During this period she received daily GCSF. Initially, post debridement she received daily granulocyte transfusions for 10 days. Caspofungin was ceased 2 weeks into treatment as her clinical condition had improved. Liposomal amphotericin continued at 5 mg/kg/

The role of immunostimulation in the treatment of invasive fungal infection

Invasive fungal infections (IFI) constitute a severe and increasing problem in an expanding patient population with immunodeficiency due to various reasons. Despite current management strategies, IFI remain a common and frequently devastating problem. New antifungals have been introduced in the medical armamentarium, but the results in patients’ survival are not yet optimal. The compromised host defense mechanisms of these patients contribute to the high failure rates. Immunoregulation includes strategies for restoration or augmentation of impaired immune responses that increase phagocytes’ number or enhance their function. Although there are extensive preclinical data, clinical investigations are very limited. Administration of certain beneficial cytokines, antibodies and other immune molecules, granulocyte transfusions, and stimulation of adaptive immunity through vaccination are potential, promising future preventive and therapeutic modalities and could be adjuncts to antifungal therapy for IFI. This review highlights and comments on preclinical and clinical studies published since 2005.

Biologic and molecular effects of granulocyte colony-stimulating factor in healthy individuals: recent findings and current challenges

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used in healthy donors for collection of peripheral blood progenitor cells (PBPCs) for allogeneic transplantation and granulocytes for transfusion. The spectrum of its biologic and molecular activities in healthy individuals is coming into sharper focus, creating a unique set of challenges and clarifying the need to monitor and safeguard donor safety. Accumulating evidence indicates that rhG-CSF effects are not limited to the myeloid cell lineage. This may reflect the presence of functional G-CSF receptors on other cell types and tissues, as well as rhG-CSF-induced modulation of cytokine networks. While most rhG-CSF-induced effects are transient and self-limiting, preliminary, provocative data have suggested the possibility of a more durable effect on the chromosomal integrity of lymphocytes. While these reports have not been validated and have been subject to criticism, they are prompting prospective studies and monitoring efforts to determine whether there is a significant risk of long-term adverse events (eg, hematologic malignancies) in healthy PBPC and granulocyte donors. Based on the totality of information that is currently available, the administration of rhG-CSF to healthy donors for the purpose of PBPC donation continues to have a favorable risk-benefit profile.

Human neutrophil alloantigens

This review describes alloantigens currently listed in the human neutrophil alloantigen (HNA) system. Review of the literature. Neutrophil antigens are implicated in a variety of clinical conditions including neonatal immune neutropenia, transfusion-related acute lung injury, refractoriness to granulocyte transfusions, febrile transfusion reactions, immune neutropenia after bone marrow transplantation, autoimmune neutropenia and drug-induced immune neutropenia. Seven antigens have been listed in the HNA system that are assigned to five antigen groups. Six antigens have been characterized biochemically and molecularly so that their primary structure is now known. As shown by regularly performed international granulocyte immunology workshops, a combination of granulocyte agglutination and immunofluorescence tests together with a panel of typed cells is currently the best means of detection. Most of the HNA antigens have been well-characterized so that HNA typing as well as the detection of the corresponding antibodies are now reliably possible. This will improve diagnostics of neutrophil antibody-mediated clinical conditions as well as the prevention of transfusion-related acute lung injury.

Non-infectious causes of elevated procalcitonin and C-reactive protein serum levels in pediatric patients with hematologic and oncologic disorders

Procalcitonin (PCT) is considered a sensitive and specific diagnostic and prognostic marker of systemic bacterial infection, but its value is questionable in certain clinical conditions, particularly in hemato-oncological patients. We analyzed PCT and C-reactive protein (CRP) levels in 56 patients of a pediatric hematology-oncology unit during 110 consecutive non-infectious febrile episodes related to administration of T-cell antibodies (group A; n = 22), alemtuzumab (monoclonal CD52 antibody, CAMPATH-1H/group B; n = 8), interleukin-2 (IL-2/group C; n = 41), prophylactic donor granulocyte transfusions (group D; n = 9), or to acute graft-versus-host disease (aGvHD/group E; n = 10) and compared the results with 20 episodes of Gram-negative sepsis (group F). In the majority of the non-infectious episodes PCT and CRP increased to serum levels statistically indistinguishable from Gram-negative sepsis. Median peak levels of PCT (normal < 0.5 ng/ml)/CRP (normal < 8 mg/l) for groups A-F were 4.34/59.0 (A), 10.14/93.5 (B), 1.11/175.0 (C), 1.43/164 (D), 0.96/34.0 (E), and 8.14 ng/ml /126.0 mg/l (F). Highest single levels were observed in groups A and F. PCT and CRP are of limited value as diagnostic markers of sepsis during T-cell-directed immunomodulatory treatment, granulocyte support, or acute GvHD.

Granulocyte concentrates: prolonged functional capacity during storage in the presence of phenotypic changes

Granulocyte transfusion has been proposed as a bridging therapy for patients with prolonged periods of chemotherapy-induced neutropenia, who suffer from severe fungal and bacterial infections. To recover, adequate numbers of granulocytes are required when the patients are refractory to standard treatment. The aim of this study was to assess the functional characteristics and efficacy of granulocyte colony-stimulating factor/dexamethasone-mobilized granulocytes used for transfusions. Granulocytes from the leukapheresis products were tested for the expression of cell-surface antigens, interactions with endothelial cells, motility, killing of microbes and survival. The granulocytes were used in vivo for transfusion in 16 severely ill children, who were--apart from a patient with a granulocyte dysfunction--all suffering from prolonged neutropenia. Mobilization of granulocytes with granulocyte colony-stimulating factor and dexamethasone caused phenotypic changes (decreased CD62L expression and increased levels of CD66b and CD177). The ability of the granulocytes to interact with endothelial cells (rolling, adhesion, transmigration) and to kill various types of pathogens was not affected by the mobilization, leukapheresis and irradiation procedures. The granulocytes were functionally indistinguishable from those isolated from untreated donors, even after 24 hours of storage. Granulocyte transfusion seemed to benefit 70% of patients, as 11 out of the 16 children showed clinical recovery within 1-2 weeks after beginning the transfusions. Although CD62L expression is downregulated on granulocytes used for granulocyte transfusions, concomitant CD177 upregulation may explain the intact interactions with endothelial cells. All other granulocyte functions tested were intact, including the ability to kill fungi. Granulocyte concentrates can be stored without loss of in vitro viability and functionality for at least 24 hours. As demonstrated in vivo, granulocyte transfusions may be an effective therapy for neutropenic pediatric patients suffering from life-threatening infections.

Human herpesvirus-6 DNAemia in immunosuppressed adult patients with leukemia at risk for mold infection

Little is known about human herpesvirus-6 (HHV-6) in leukemia patients. We prospectively followed 37 leukemia patients at risk for mold infection. HHV-6 DNA was detected from whole blood specimens in 11 patients (30%). History of granulocyte transfusions (p=0.05) and prior relapse of leukemia (p=0.07) were the only independent predictors of HHV-6 DNAemia.

Effective management of pulmonary aspergillosis invading the thoracic spine in a child with high risk ALL requiring allogeneic bone marrow transplantation

Due to unacceptably high mortality, invasive fungal infections (IFI) have long been considered a contraindication against allogeneic stem cell transplantation. Despite severe immunosuppression an 11-year-old girl requiring allogeneic bone marrow transplant (BMT) for relapsed acute lymphoblastic leukemia was cured of a concurrent invasive pulmonary aspergillosis. Treatment comprised combinations of liposomal amphotericin B, caspofungin and voriconazole with donor granulocyte transfusions. This therapeutic regimen, including the choice of reduced intensity conditioning (RIC), allowed the patient to receive an allogeneic BMT. In hematological remission the child later developed fatal chronic graft-versus-host disease. Combined antifungal treatment and granulocyte support allow for effective management of IFI even in allogeneic stem cell transplant recipients. However, short-term benefits of RIC may be outweighed by late complications.

Absidia corymbifera in a Patient With Chronic Granulomatous Disease

To the Editors: In the review article on zygomycosis in children by Zaoutis et al1 it is clearly outlined that this rare but life-threatening infection does occur in individuals with predisposing factors, such as neutropenia in hematopoietic stem cell transplant recipients and patients with hematological malignancies, diabetes mellitus, burns, surgery and trauma, desferoxamine therapy, as well as certain “pediatric-specific” conditions such as high-risk premature newborns, juvenile-onset (type 1) diabetes mellitus with uncontrolled diabetic ketoacidosis, and congenital metabolic aciduria. We have recently been surprised by finding widespread Absidia corymbifera infection on postmortem of a 14-year-old boy who presented 1 month before he died with signs and symptoms of acute community-acquired pneumonia. With worsening respiratory function despite broad-spectrum antibiotics, and with no diagnosis established of the underlying disease despite extensive investigations before developing adult respiratory distress syndrome requiring mechanical ventilation and treatment with high-dose steroids, he was referred for emergency support with extracorporeal mechanical oxygenation (ECMO). Open lung biopsy at that stage revealed Aspergillus fumigatus invasive pneumonia and the dihydrorhodamine neutrophil oxidative burst flowcytometry assay was diagnostic for chronic granulomatous disease (CGD), subsequently confirmed to be a result of p47phox mutation. The past medical history was uneventful except that he helped cleaning gutters of dead leaves the week before he presented. Despite combined antifungal (voriconazole and caspofungin) therapy, γ-interferon, and granulocyte transfusions, he died of multiorgan system failure. This case was reported recently as patient 1 of the series of 9 patients describing the newly recognized emergency presentation of CGD, the “fulminant mulch pneumonitis.”2 Other patients in that series, all exposed to recent inhalation of mulch, had multiple fungal infections besides Aspergillus spp., mainly with Rhizopus spp., another of the Zygomycetes class, and Penicillium spp. However, we could not find any previous reports of A. corymbifera infection in CGD, neither is that mentioned in the recent extensive review on fungal infections in primary immunodeficiency.3 Mario Abinun, MD Department of Paediatric Immunology Chris Wright, FRCPath Department of Histopathology Kate Gould, FRCPath Department of Microbiology Terence J. Flood, MA, MRCPI Department of Paediatric Immunology Jane Cassidy, MRCP Department of Paediatric Intensive Care Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne United Kingdom

Outcome with Hyper-CVAD/MTX-Ara-C, a Dose-Intensive Regimen, in Acute Lymphocytic Leukemia and Highly Aggressive Lymphoma in China.

Purpose: The objective of this study was to evaluate the efficacy and potential toxicity of the Hyper-CVAD/MTX-Ara-C regimen,a dose-intensive regimen, in the patients with acute lymphocytic leukemia (ALL) and highly aggressive non-Hodgkin lymphoma (NHL) in China.PATIENTS AND METHODS: Between June 2004 and June 2007, fifty-six patients with ALL or highly aggressive lymphoma were treated with the Hyper-CVAD/MTX-Ara-C regimen at our institution. Median age was 26 years (range 13 to 60 years), and 35 patients (62.50%) were male. All patients were comprised of 32 previously untreated cases and 24 refractory/relapsed ones. Among the 41 patients with ALL, B-cell disease was present in 82.93%, T-cell disease in 17.07%, and Ph-positive ALL was present in 14.63%, refractory/relapsed disease in 43.90%. Among the 15 patients with highly aggressive NHL, lymphoblastic lymphoma was present in 46.67%, Burkitt's lymphoma was in 53.33% and refractory/relapsed disease in 40.00%. CNS involvement was present in 8% at diagnosis. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and aggressive supportive care with granulocyte colony-stimulating factor (G-CSF), transfusion and antibiotic prophylaxis therapy. Maintenance therapy based on cytogenetics and immunophenotypes in most of patients contained 2-year treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP).RESULTS: The median follow-up time was 7 months (range 1+ to 37+ months). Of the previously untreated 31 patients, twenty-nine patients (93.55%) achieved complete remission (CR) and no patients died during induction therapy. Of the refractory /relapsed 24 patients, fourteen cases (58.33%) achieved CR. Remarkably, the CR rate of the patients with Burkitt's lymphoma was 75.00% (6/8). The median courses finished during the dose-intensive phase were 4 (range 1 to 8), and the median time to delivery of all eight courses was 10 months. The estimated 3-year overall survival (OS) for the untreated and refractory/relapsed patients with ALL was 46.80% and 28.60%, respectively. Meanwhile, the estimated 2-year OS for the aggressive NHL patients was 84.00%. Compared with the patients with ALL who did not receive CR and get less than four courses of this regimen, the patients who did receive CR and get more than four courses of this dose-intensive regimen showed much better OS (p<0.05). The incidence of CNS relapse was low (5%). Myelosuppression-associated complications including documented infections, fever of unknown origin, hemorrhage were the more frequent side effects. Other significant side effects included neurotoxicity, renal and hepatic toxicities, fatigue, mucositis, nausea, vomiting, diarrhea, skin rashes, and G-CSF therapy-associated bone aches.CONCLUSION: The present outcome from our single center in China demonstrated that Hyper-CVAD/MTX-Ara-C, a dose-intensive regimen with much higher CR was superior to our previous regimens, even in patients with highly aggressive lymphoma such as lymphoblastic and Burkitt's lymphoma, and in refractory/relapsed ALL/lymphoma ones. Our study also showed that this regimen was less toxic and well tolerated in most of treated patients in China. Long-term treatment benefits and severe side effects needed further investigation in a well-designed, multiple-center study in China with more eligible patients entering onto the study.

Granulocyte transfusions for neutropenic patients with life‐threatening infections: a single centre experience in 47 patients, who received 348 granulocyte transfusions

The role of granulocyte transfusions (GT) in patients with neutropenia-related infections remains controversial. A retrospective analysis of 47 neutropenic patients, treated with 348 consecutive GTs for life-threatening infections between 1999 and 2004, is presented. The only grade III-IV toxicity observed in GT recipients was respiratory deterioration (n = 6, 12.8%). The overall infection-related mortality (IRM) approached 38%. Achievement of a neutrophil count of > 700 cells per microl after at least 50% of days of GTs (n = 33, 70%) significantly correlated with reduced IRM (27.3% vs. 64.3%, P < 0.02). GT doses of > 2 x 10(10) neutrophils per bag appeared to increase both neutophil and platelet counts following transfusion. GTs are safe and should be considered for patients with life-threatening neutropenic infections. However, prospective randomized studies of GTs are the only way to establish the true role of GTs.

Optimal ex vivo expansion of neutrophils from PBSC CD34+ cells by a combination of SCF, Flt3-L and G-CSF and its inhibition by further addition of TPO

BackgroundAutologous mobilised peripheral blood stem cell (PBSC) transplantation is now a standard approach in the treatment of haematological diseases to reconstitute haematopoiesis following myeloablative chemotherapy. However, there remains a period of severe neutropenia and thrombocytopenia before haematopoietic reconstitution is achieved. Ex vivo expanded PBSC have been employed as an adjunct to unmanipulated HSC transplantation, but have tended to be produced using complex cytokine mixtures aimed at multilineage (neutrophil and megakaryocyte) progenitor expansion. These have been reported to reduce or abrogate neutropenia but have little major effect on thrombocytopenia. Selective megakaryocyte expansion has been to date ineffective in reducing thrombocytopenia. This study was implemented to evaluate neutrophil specific rather than multilineage ex vivo expansion of PBSC for specifically focusing on reduction or abrogation of neutropenia.MethodsCD34+ cells (PBSC) were enriched from peripheral blood mononuclear cells following G-CSF-mobilisation and cultured with different permutations of cytokines to determine optimal cytokine combinations and doses for expansion and functional differentiation and maturation of neutrophils and their progenitors. Results were assessed by cell number, morphology, phenotype and function.ResultsA simple cytokine combination, SCF + Flt3-L + G-CSF, synergised to optimally expand and mature neutrophil progenitors assessed by cell number, phenotype, morphology and function (superoxide respiratory burst measured by chemiluminescence). G-CSF appears mandatory for functional maturation. Addition of other commonly employed cytokines, IL-3 and IL-6, had no demonstrable additive effect on numbers or function compared to this optimal combination. Addition of TPO, commonly included in multilineage progenitor expansion for development of megakaryocytes, reduced the maturation of neutrophil progenitors as assessed by number, morphology and function (respiratory burst activity).ConclusionGiven that platelet transfusion support is available for autologous PBSC transplantation but granulocyte transfusion is generally lacking, and that multilineage expanded PBSC do not reduce thrombocytopenia, we suggest that instead of multilineage expansion selective neutrophil expansion based on this relatively simple cytokine combination might be prioritized for development for clinical use as an adjunct to unmanipulated PBSC transplantation to reduce or abrogate post-transplant neutropenia.

Correction of chronic granulomatous disease after second unrelated‐donor umbilical cord blood transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for chronic granulomatous disease (CGD), but many patients lack a suitably matched related donor. We report successful outcomes after mismatched, unrelated-donor umbilical cord blood transplantation (uUCBT) in two boys with X-linked CGD. Both patients experienced autologous recovery after first transplants, required second transplants to achieve durable donor engraftment, and are alive 27 and 15 months post-transplant. Both had invasive fungal disease and received granulocyte transfusions. In conclusion, uUCBT is effective in children with CGD, but immunosuppression in the conditioning regimen may need to be increased to decrease the risk of graft rejection.

Granulocyte transfusions in neutropaenic children: A systematic review of the literature

Background Granulocyte transfusions (GTX) have been used for decades in paediatric neutropaenic patients, but uncertainty remains regarding their effectiveness. We reviewed all the paediatric data available on GTX, to gain a insight in to the indications for use, favourable effects and side effects in patients and donors. Methods A comprehensive search was done in MEDLINE, EMBASE, LILACS and CENTRAL (1966 until 2006). All studies including children (1–18 years) who received GTX were included. Results A total of 66 observational studies were included:Seven using prophylactic and 59 therapeutic GTX. Of the therapeutic studies 55 reported a proven sepsis caused by Gram-negative bacteria (34%) or fungal disease (48%) as the indication for GTX. Concerning effectiveness 70% survival was reported, but no controlled studies were identified. Side effects were mentioned in 27 studies including mild respiratory symptoms, allergic reactions and infection related complications (CMV). Side effects in the donor were mainly flu-like illness. Discussion In this first review covering 30 years of experience on the use of GTX in children, we found no randomised evidence showing a positive benefit risk ratio. The available case reports and cohort studies alert us as to the potential benefits and harms of the use of GTX in neutropaenic children and provides the basis for a well designed trial in children.

Dramatic tissue response after a single granulocyte transfusion

TransfusionVolume 47, Issue 12 p. 2185-2186 Dramatic tissue response after a single granulocyte transfusion Shlomit Ein-Gal, Shlomit Ein-Gal From Cedars-Sinai Medical Center, Los Angeles, California.Search for more papers by this authorSamuel H. Pepkowitz, Samuel H. Pepkowitz From Cedars-Sinai Medical Center, Los Angeles, California.Search for more papers by this authorCarole H. Hurvitz, Carole H. Hurvitz From Cedars-Sinai Medical Center, Los Angeles, California.Search for more papers by this authorDennis Goldfinger, Dennis Goldfinger From Cedars-Sinai Medical Center, Los Angeles, California.Search for more papers by this author Shlomit Ein-Gal, Shlomit Ein-Gal From Cedars-Sinai Medical Center, Los Angeles, California.Search for more papers by this authorSamuel H. Pepkowitz, Samuel H. Pepkowitz From Cedars-Sinai Medical Center, Los Angeles, California.Search for more papers by this authorCarole H. Hurvitz, Carole H. Hurvitz From Cedars-Sinai Medical Center, Los Angeles, California.Search for more papers by this authorDennis Goldfinger, Dennis Goldfinger From Cedars-Sinai Medical Center, Los Angeles, California.Search for more papers by this author First published: 21 August 2007 https://doi.org/10.1111/j.1537-2995.2007.01444.xCitations: 2 Shlomit Ein-Gal, MD, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048; e-mail: [email protected]. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume47, Issue12December 2007Pages 2185-2186 RelatedInformation

Leukocyte adhesion deficiency type 1: an important consideration in the clinical differential diagnosis of prepubertal periodontitis. A case report and review of the literature

Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects 1 in 1 million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. Features of this disease result from mutations in the region of the CD18 gene, which is encoded on chromosome 21q22.3. This gene codes for the common subunit of the leukocyte integrins LFA-1, Mac 1, and p150,95. Failure to produce a functional subunit results in the defective expression of all 3 leukocyte integrins, and the leukocytes of LAD have subnormal adhesion properties. We present a case of the moderate-to-severe form of LAD in a 3-year-old girl who initially presented with generalized swelling and erythema of the gingiva, with slight tooth mobility and a nonhealing labial ulceration. Her medical history was significant for recurrent urinary tract infections. Periodontal pathogens, including Capnocytophaga, Eikenella corrodens, and Candida albicans, were cultured. The patient had a significantly elevated white blood cell count and absolute neutrophil count. The diagnosis of LAD was confirmed with flow cytometry, which revealed significantly decreased subunits. Twenty-four months after the diagnosis was made and after a series of granulocyte transfusions and bone marrow transplantations, she expired as the result of respiratory failure.

Minimizing the risk of recurrent or progressive invasive mold infections during stem cell transplantation or further intensive chemotherapy

The risk of recurrence or progression of prior invasive fungal infection, predominantly due to molds, is 11-33% during subsequent stem cell transplantations or myelosuppressive chemotherapy, with a high mortality. Risk factors at the time of transplant include active infection and having received <6 weeks of antifungal therapy, while after transplant prolonged neutropenia and graft-versus-host disease requiring aggressive immunosuppression are important. The use of peripheral blood stem cells has been associated with a lower risk. Minimal data are available regarding the role of preventative strategies such as surgical resection of pulmonary lesions and prophylactic granulocyte transfusions during neutropenia, the optimal duration of antifungal prophylaxis, and the appropriate monitoring strategy. This article critically evaluates these issues and provides recommendations for the secondary prophylaxis of invasive mold infections.

Immunomodulatory therapy in yeast infections

Invasive yeast infections are a significant cause of morbidity and mortality in patients with defective immune response, such as those with cancer-related immunosuppression, organ transplantation or other immunodeficiencies, and neonates. Hospitalization in the intensive care unit may increase the risk for such infections. Despite the advent of new antifungal agents, the problem is escalating as the number of susceptible hosts increase and virulent, more resistant fungal strains emerge. Over the past few years, advances in immunology and molecular biology have greatly contributed to a better understanding of the pathogenesis of yeast infections. There is evidence that reconstitution of the host immune function is a major contributor to the resolution of yeast infections. Strategies aiming to increase the phagocyte number (e.g., granulocyte transfusions), to stimulate immune response (e.g., administration of hematopoietic growth factors and other proinflammatory cytokines) and to stimulate antigen-specific immunity (e.g., antibody therapy or vaccination) benefit patients at risk of, or suffering from, yeast infections. Further preclinical and clinical studies, as well as improving our understanding of immune system functions and dysfunctions, remain a future challenge.

Successful Stem Cell Transplantation without Cryopreservation from a Microchimeric Haploidentical Sibling for Refractory Acute Myeloid Leukemia Complicated with Critical Thrombophlebitis and Cellulitis

We describe the case of a 38-year-old male patient who had acute myeloid leukemia and developed prolonged neutropenia after induction chemotherapy. He developed thrombotic complications at multiple sites. Thrombophlebitis of the hemorrhoidal plexus became exacerbated and developed into critical cellulitis. Because the patient had no human leukocyte antigen-identical sibling, we considered an alternative donor. Because of the necessity for early neutrophil recovery to resolve the critical infection, we proceeded with allogeneic peripheral blood stem cell transplantation (PBSCT) from a microchimeric haploidentical sibling donor. We infused peripheral blood mononuclear cells directly into the patient without cryopreservation and thawing procedures. We aimed for the contaminating granulocytes to act as a granulocyte transfusion. Actually, the neutrophils increased to 1.6 x 10(9)/L on day 1, when the patient showed a temporary resolution of infection. Engraftment was achieved shortly after neutropenic nadir, and acute graft-versus-host disease (GVHD) has been well controlled. Although the patient experiences extensive chronic GVHD, he has been well as an outpatient with a 90% Karnofsky performance status score. The leukemia has been in complete remission for more than 1 year. These findings suggest the clinical utility of a salvage therapy with allogeneic PBSCT from a microchimeric haploidentical donor to treat refractory leukemia concurrent with life-threatening infection.