Non-malignant Hematological Diseases Research Articles

Graft-versus-Host-Disease after Double Cord Blood Transplantation: A New Look at Its Characteristics

Umbilical cord blood transplantation (UCBT) has become a widely available and accepted alternative stem cell source for pediatric and adult patients with malignant and nonmalignant hematologic diseases [1-4]. Over the last several years, multiple studies have reported lower rates of graft-versus-host disease (GVHD), both grade III-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD), in UCBT recipients compared with recipients of unrelated donor peripheral blood or bone marrow hematopoietic cell transplantation (HCT) [5-7]. However, the more recent decreased use of antithymocyte globulin as part of the conditioning regimen, the almost uniform use of combination cyclosporine and mycophenolate mofetil therapy for GVHD prophylaxis, and the increased use of 2 cord blood units (versus 1 unit) warrant a reevaluation of the incidence of aGVHD and cGVHD after UCBT. Furthermore, the rate of cGVHD reported after UCBT in the previous studies was determined using the traditional clinical diagnostic criteria (limited versus extensive), without taking in consideration the 2005 National Institutes of Health (NIH) consensus criteria [8]. Ponce et al. [9] conducted a single-center study in 115 pediatric and adult patients with hematologic malignancies who underwent double UCBT (dUCBT) to assess the incidence and manifestations of both aGVHD and cGVHD. The authors reported an incidence of grade II-IV acute GVHD of 53% at day þ180, which was similar to the rate previously reported by MacMillan et al. [5]. However, the data of Ponce et al. identify the gastrointestinal (GI) tract, not the skin, as the most commonly affected organ, with GI involvement in 80% of patients with grade II-IV aGVHD. This finding confirms previously reported results in a cohort of 79 pediatric UCBT recipients [10]. The propensity of isolated GI aGVHD reinforces the importance of using endoscopic biopsy for diagnosis when symptoms are limited to this single organ system.

Overexpression of eIF4E gene in acute myeloid leukemia and its relation with disease progression

The aim of this study was to detect the expression level of eIF4E gene in patients with non-treated, remission and non-remission/relapse acute myeloid leukemia (AML), and other non-malignant haematologic diseases so as to analyze and reveal the relationship of eIF4E gene expression with AML progression. SYBR Green I RT-PCR was used to assay the expression level of eIF4E mRNA extracted from bone marrow mononuclear cells in 30 patients with AML (6 in M2, 5 in M3, 8 in M4, 10 in M5, 1 in M6) and 20 patients with non-malignant hematologic diseases. The β2-microglubin(β2M) was used as internal reference and the formula 2(-ΔCt)×100% was applied to calculate the expression level of eIF4E gene. The results showed that the eIF4E expression level (7.098 ± 5.544)% in patients with non-treated and non-remitted/relapsed AML was significantly higher than that in patients with remission (0.964 ± 0.312)% (P < 0.01) and non-malignant hematologic diseases (0.248 ± 0.163)% (P < 0.01). There was no difference between latter two group patients, even though the expression level of eIF4E gene in patients with M4 and M5 was higher. As compared with non-malignant hematologic diseases, the expression level of eIF4E gene of patients with remission patients showed no significant difference. It is concluded that the over-expression of eIF4E gene has been found in patients with AML, and its level obviously decreases along with remission of disease, thus the eIF4E gene may be a surveillance parameter for disease progression.

Administration of Hydrogen-Rich Saline Protects Mice From Lethal Acute Graft-Versus-Host Disease (aGVHD)

Allogeneic hematopoietic stem cell transplantation is a potentially curative therapy for many malignant and nonmalignant hematologic diseases. However, acute graft-versus-host disease (aGVHD) is a lethal complication of hematopoietic stem cell transplantation, which limits its application. Cytokines such as tumor necrosis factor-α and interleukin-6 play an extremely important role in the formation and development of aGVHD. Reactive oxygen species, such as hydroxyl radicals, also play an important role in the formation and development of aGVHD. In recent years, hydrogen was reported to have an ability to inhibit the levels of cytokines, such as tumor necrosis factor and interleukin-6 in vivo, and it also has a strong selective free radical-scavenging ability. Therefore, we hypothesized that hydrogen may have therapeutic effects on aGVHD. To determine whether hydrogen could protect mice from lethal GVHD in a major histocompatibility complex-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated and leukocyte counts were also determined after BMT. We also examined serum cytokine levels and scored clinical signs of GVHD mice after BMT. This article demonstrated that the administration of hydrogen-rich saline increased the survival rate and clinical score of aGVHD mice. Administration of hydrogen-rich saline after transplantation also promoted the recovery of white blood cells of aGVHD mice. However, there was no report on the therapeutic effects of hydrogen on aGVHD. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on aGVHD.

Biology of Graft-versus-Host Responses: Recent Insights

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many malignant and non-malignant hematological diseases. The curative effect of allo-HSCT results from both the chemotherapy and/or radiation in the conditioning regimen and the donor T mediated graft-versus-host (GVH) response against the malignancy known as a graft-versus-leukemia (GVL) effect. In most cases, the GVH response is not limited against the malignant cells, but also mediated against host epithelial cells causing graft-versus-host disease (GVHD). The safety and effectiveness of allogeneic transplants has increased substantially over the last several years. Despite the progress, GVHD and relapse remain the biggest hurdles for a more widespread and effective use of this potent therapy. Experimental data from recent years have provided deeper and better insights into the process of GVH responses. Emerging data have refined our understanding of the role of antigen presenting cells (APC) in GVHD. Novel molecular targets have been identified in donor T cell subsets and host non-hematopoietic cells that can potentially be exploited for mitigating GVHD and to better harness GVL. During recent years the role of various cytokines in GVHD continues to be explored. This work has led to improved understanding of potential causes for tissue specificity of GVHD. The role of host and donor microbiome in regulating GVH responses has been a subject of intense focus as well. Notable advances have been made in the defining various other aspects of GVH responses , but these go beyond the scope of this brief review. Herein we will focus on three specific aspects of GVH responses, namely 1) the evolving role of hematopoietic APCs as the regulators of GVHD, 2) novel strategies for enhancing GVL responses and 3) the recently identified molecular targets for mitigating GVH responses.

Mixed donor chimerism in non-malignant haematological diseases after allogeneic bone marrow transplantation.

To determine the frequency of mixed donor chimerism in patients of non-malignant haematological diseases after allogeneic bone marrow transplant. A cross-sectional, observational study. Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July 2010 to June 2011. Donor chimerism was assessed in patients of aplastic anaemia and beta-thalassaemia major who underwent allogeneic bone marrow transplantation (BMT). Peripheral blood samples were used to assess chimerism status by analysis of short tandem repeats (STR). In patients where pre-transplant blood sample was not available, swab of buccal mucosa was used for pre-transplant STR profile. A standard set of primers for STR markers were used and the amplified DNA was resolved by gel electrophoresis and stained with silver nitrate. The percentage of donor origin DNA was estimated by densitometer. Out of 84 patients, 52 (62%) were males, while 32 (38%) were females. In patients of beta-thalassaemia major, 31 (62%) developed mixed donor chimerism (MC), 13 (26%) developed complete donor chimerism (CC) and 6 (12%) had graft failure. In aplastic anaemia, 17 patients (50%) achieved MC, 13 (38.2%) had CC and 4 (11.8%) developed graft failure. The combined frequency of mixed donor chimerism for both the diseases was 58.3%. D3S1358 was the most informative STR marker in these patients. Majority of the studied patients developed mixed donor chimerism following bone marrow transplantation, whereas only a minor percentage of the patients had graft failure. Analysis of D3S1358 was the most informative in assessing donor chimerism in patients who underwent BMT.

CD26 protease inhibition improves functional response of unfractionated cord blood, bone marrow, and mobilized peripheral blood cells to CXCL12/SDF-1

Hematopoietic stem cell transplantation (HSCT) is an important treatment option for patients with malignant and nonmalignant hematologic diseases. Methods to improve transplant efficiency are being explored with the intent to improve engraftment and immune reconstitution post-HSCT. A current approach under investigation involves treatment of donor cells with inhibitors that target the protease CD26, a negative regulator of the chemokine CXCL12/stromal cell-derived factor-1. CD26 inhibitor treatment has been shown to improve the functional response of CD34(+) cord blood (CB) cells, but not CD34(+) granulocyte colony-stimulating factor-mobilized peripheral blood stem cells, to CXCL12/stromal cell-derived factor-1. The effect of CD26 inhibitors on unfractionated CB, bone marrow, or granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells has not been evaluated previously. We observed that although CB had greater CD26 expression than bone marrow or mobilized peripheral blood, treatment with a CD26 inhibitor (Diprotin A) resulted in increased responsiveness to stromal cell-derived factor-1 for all three mononuclear cell sources tested. This suggests that clinical therapeutic benefit might be gained by using CD26 inhibitors as a strategy to improve engraftment of unfractionated mobilized peripheral blood cells as well as CB cells.

Transforming growth factor‐β1 polymorphisms and the outcome of hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is a medical procedure used to treat malignant and nonmalignant haematological diseases, congenital immunodeficiency syndromes, solid tumours and metabolic diseases. Despite its usefulness, several major complications, such as graft-versus-host disease, can negatively affect patients treated with HSCT. Apart from clinical factors well known to affect the outcome of HSCT, patient and donor genetics have been shown to play an important role in the susceptibility to post-transplant complications. Histocompatibility as determined by the human leucocyte antigen (HLA) system has been a major genetic determinant of the success of HSCT. Non-HLA immunogenetics are increasingly recognized to play a part in the events related to transplantation. Cytokine genes, and their receptors, bear a considerable amount of polymorphism. One of the genes that may play an important role on the outcome of allogeneic HSCT is TGFB1, which encodes transforming growth factor, βeta 1 (TGF-β1). TGF-β1 is a pleiotropic cytokine, which plays a central role in the development, homeostasis and responses of the immune system. Several functional polymorphisms in TGFB1 have been identified, and these are known to cause alterations in cytokine secretion in several settings. The present review will focus on the current knowledge surrounding the effect of polymorphisms within TGFB1 on the outcome of HSCT.

Targeting Memory T Cells with Alefacept to Abrogate Transfusion Alloimmunization: Preliminary Results from a Trial of Reduced Intensity Conditioning and Allogeneic Transplant for Children with Non-Malignant Hematologic Diseases

Targeting Memory T Cells with Alefacept to Abrogate Transfusion Alloimmunization: Preliminary Results from a Trial of Reduced Intensity Conditioning and Allogeneic Transplant for Children with Non-Malignant Hematologic Diseases

Percutaneous vertebroplasty for osteoporotic vertebral fracture in a patient with sickle cell disease.

Percutaneous vertebroplasty (PVP) is a procedure in which bone cement is injected into vertebrae under fluoroscopic guidance. It was reported to be effective and safe for the treatment of back pain due to compression fractures of the spine [1,2]. As PVP has been successfully used to treat compression fractures of the spine in patients with malignant and non-malignant hematologic diseases, we thought that it might also be beneficial for patients with sickle cell disease (SCD) that have vertebral compression fractures.

Concise Review: Cord Blood Banking, Transplantation and Induced Pluripotent Stem Cell: Success and Opportunities

Hematopoietic cell transplantation (HCT) has become a standard practice to treat a number of malignant and nonmalignant hematologic diseases. Bone marrow, mobilized peripheral blood, and umbilical cord blood can all serve as primary sources of cells for HCT. The number of cord blood units currently stored is large, although it represents only a fraction of potential collections. With much of the collection being sequestered in private banks for possible autologous use, there is a reason to expect that public banks may not be able to provide for the demand in coming years as use of cord blood for treatment of patients with diseases such as leukemia and lymphoma continues to increase. We suggest that a possible solution to encourage private banks to share their valuable units is to apply recent methodologies to generate induced pluripotent stem cells from cord cells and to optimize techniques to generate hematopoietic lineages from them. This strategy would allow us to take advantage of the units already collected under appropriate regulatory guidelines, to access a pristine cell that can be converted to a pluripotent cell at a much higher efficiency and in a shorter time period than other cells. The ability to potentially replenish a used cord unit with new cells, as well as extend the potential utility of cord blood for additional therapeutic applications, should allow banks to develop an appropriate business model for both private and public cord blood banks to flourish.

Quality of Cord-Blood Units and Hematological Recovery After Intra Bone CBT Are Not Influenced by the Bank of Origin and by the Time of Cryopreservation

Abstract 4400 BACKGROUND:Cord-blood transplantation (CBT) is an effective option for both malignant and non-malignant hematological diseases and its increasing number in the last years has enlarged the frequency of the use of cord-blood units (CBUs) trough international borders in order to maximize the opportunity of identifying optimal CB unit. Since there is no global standard regarding cord-blood quality control, the quality of CBUs can be affected by the bank of origin. In addition, few information are disposable on the cord blood engraftment capacity after long-term cryopreservation. In this study, we evaluated whether the origin and the age of CBUs may influence the quality of CBUs and post-transplant hematological recovery. METHODS:CBTs with single unit were performed at San Martino Hospital in Genoa for hematological malignancies using an intra-bone cord blood transplant technique. Just before infusion, a small sample of the CBU was obtained and post-thawing number of total nucleated cells (TNCs), CD34 positive cells, and colony-forming cells (CFCs) were characterized. Median pre-freezing number of TNCs and CD34-positive cells were 2.32 (1.15 – 4.52) × 109 and 9.3 (2.4 – 27.24) × 106, respectively. Recovery of neutrophil and platelet were compared according to the origin and the age of each CBU. RESULTS:95 CBUs were tested. The bank of origin of CBUs was Europe (n = 45), the United States (n = 40), and other regions (n = 10). Median age of CBUs was 4.9 (0.4 – 11.8) years; CBUs originated from European bank were significantly older than CBUs from other regions (5.9 years vs 3.8 years, p value of unpaired t-test < 0.001). Median post-thawing number of TNCs, CD34 positive cells, and CFCs were 2.3 (0.74 – 4.5) × 109 cells, 1.1 (0.23 – 2.7) × 107 cells, and 1.8 (0.0 – 12) × 106 cells, respectively. These values did not differ considering older (> 4.9 years) CBUs or younger CBUs (< 4.9 years) or the bank of origin. Rate and median time of neutrophil and platelet engraftment was as follows: younger CBUs: 24 and 34 days, older CBUs: 25 and 35 days, respectively (Figure 1,3). Hematological recovery was not influenced by the bank origin of CBUs as well, namely, rate and time of neutrophil and platelet engraftment was, 22 and 34.5 days (Europe), 22 and 35 days (the United States), 24 and 42 days (the other region), respectively (Figure 2,4). CONCLUSION:Although in our experience time of cryopreservation of CBUs was significantly dependent from bank of origin, the origin and the age of CBUs have little impact on post-thawing values of TNCs, CD34 positive cells, and CFCs. In addition, hematological recovery after transplant was not influenced by the origin or by the age of CBU. These data suggest that quality control of CBU is working well regardless of the bank origin. Disclosures:No relevant conflicts of interest to declare. [Display omitted] [Display omitted]

Treatment of Steroid Resistant Grade II to IV Acute Gvhd by Infusion of Mesenchymal Stroma Cells Expanded with Human Plasma and Platelet Lysate - a Phase I/II Study

Abstract 3046Introduction For numerous malignant and non-malignant hematological diseases allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy. However, a major complication is the acute graft versus host disease (aGVHD), which is life-threatening and substantially reduces efficacy of HSCT. In particular, the outcome for patients with severe steroid-resistant aGVHD is very poor. Therefore, it remains important to search for new therapeutic strategies for the treatment of aGVHD.Objective Feasibility of the generation mesenchymal stroma cells (MSCs) expanded with human plasma and platelet lysate (hPPL) was tested as well as the feasibility and safety of the application of MSCs in patients with steroid-refractory extensive aGVHD.Method In an open-label, non-randomized prospective phase I/II study MSCs were extracted from the bone marrow of healthy volunteers, expanded with human plasma and platelet lysate (hPPL), and stored. Patients with steroid-refractory extensive aGVHD were treated with ∼2×106/kg MSC. Response rate, transplantation-related deaths, and other adverse events were assessed for up to 12 months after the last infusion of the cells.Results Between January 2009 and December 2010, 18 patients were treated, 5 children and 13 adults, median age was 32.5 years (range 1.3–65.9). Organ involvement of the aGVHD was 67% skin, 83% gastro-intestinal and 28% liver. Overall grade was II for 4 (22%), III for 13 (72%), and IV for 1(6%) patients. 1 patient received one infusion, all other patients received two or more infusions. No patient had side-effects during or immediately after infusions of the MSC. Median follow-up was 5.5 months (range 0.33–12). Complete overall response was observed in 11 (61%) patients after a median of 65 days (range 10–184 days). The overall survival was significant better (p <0.001) compared to non-responders. Of the 11 patients who reached a CR, 8 relapsed median 59 days (1–244) after reaching CR. Three children with subsequently limited cGVHD, allo immune lung and auto-immune cytopenia and 5 adults with all relapse GVHD of the gut, median 98 days (35–302 days). However, GVHD of the gut was then sensitive for the treatment with steroids. Overall, 7 patients died, 4 due to progression of aGVHD, 1 patient due to abdominal bleeding and 2 due to sepsis.Conclusion Generation and infusion of MSCs in steroid-resistant aGVHD grade II- IV is a feasible, safe and very effective. In addition, also patients who initially responded to MSCs but develop later a relapse of aGVHD during tapering or cessation of immunosuppressive drugs become again sensitive to the treatment with steroids. Disclosures:No relevant conflicts of interest to declare.

Cellular therapies supplement: strategies for improving transplant efficiency in the context of cellular therapeutics

The field of hematopoietic stem cell transplantation (HSCT) has overcome many obstacles that have led to our current clinical ability to utilize cells collected from marrow, mobilized peripheral blood, or umbilical cord blood for the treatment of malignant and nonmalignant hematologic diseases. It is in this context that it becomes evident that future progress will lie in our development of an understanding of the biology by which the process of HSCT is regulated. By understanding the cellular components and the mechanisms by which HSCT is either enhanced or suppressed it will then be possible to design therapeutic strategies to improve rates of engraftment that will have a positive impact on immune reconstitution post-HSCT. In this review we focus primarily on allogeneic hematopoietic stem cell transplantation (allo-HSCT), the current challenges associated with allo-HSCT, and some developing strategies to improve engraftment in this setting.

Proteine in der Hämatologie

The introduction of monoclonal antibodies has been a milestone in the treatment of hematologic neoplasms. The CD20 antibody rituximab has been a trailblazer and represents meanwhile a fixed combination partner of different first- and second-line chemotherapies in CD20-positive B-cell-non-Hodgkin's lymphoma (NHL). Rituximab maintenance is established in follicular lymphoma. The drug is also used for the treatment of non-malignant hematologic diseases (i.e. immunthrombocytopenia). Rituximab was followed by the CD52 antibody alemtuzumab and recently by the CD20 antibody ofatumumab for the therapy of CLL and the radioimmunconjugate ibritumomab-tiuxetan indicated for the treatment of refractory or relapsed CD20-positive follicular lymphoma or as consolidation after induction chemotherapy. In the near future, approval of several new antibodies is expected. For the treatment of refractory or relapsed Hodgkin's lymphoma and relapsed systemic anaplastic large cell lymphoma, the CD30 antibody brentuximab vedotin has been shown to be a highly active new treatment option.

Can the response to 23-valent pneumococcal vaccine in splenectomised patients be predicted?

The 23-valent pneumococcal vaccine has unequal effectiveness in splenectomised patients. We performed a longitudinal study (2005-2008) whose main objective was to characterize the profile of non-responders among splenectomised patients treated at our institution and identify potential predictive indicators of the response to the vaccine. The immune response was evaluated in 96 subjects. The proportion of responders was 70% (95% CI: 60-78%). Immunosuppression (OR=3.19, 95% CI 1.04-9.73) and the reason for splenectomy (hematologic neoplasia versus non-malignant hematologic diseases, OR=7.37, 95% CI 1.71-31.7) were independent predictors of non-response to vaccination. However, the positive predictive value of the model and the likelihood ratio for a positive result were low (PPV=76.6%, 95% CI 66.2-84.4%, LR(+)=1.41, 95% CI 1.08-1.86). We recommend determining the response to pneumococcal vaccine in these patients when possible.

Targeting Cannabinoid Receptors as a Novel Approach in the Treatment of Graft-versus-Host Disease: Evidence from an Experimental Murine Model

Allogeneic hematopoietic cell transplantation (HCT) is widely used to treat patients with life-threatening malignant and nonmalignant hematological diseases. However, allogeneic HCT often is accompanied by severe and lethal complications from graft-versus-host disease (GVHD), in which activated donor T cells recognize histocompatibility antigenic mismatches and cause significant toxicity in the recipient. In the current study, we tested the hypothesis that activation of cannabinoid receptors on donor-derived T cells may prevent GVHD. We tested the effect of Δ(9)-tetrahydrocannabinol (THC) in an acute model of GVHD that was induced by transferring parental C57BL/6 (B6) spleen cells into (C57BL/6 × DBA/2) F(1)(BDF1) mice. Transfer of B6 cells into BDF1 mice produced severe acute GVHD in the recipient, characterized by lymphoid hyperplasia, weight loss, T helper l cytokine production and mortality. THC administration led to early recovery from body weight loss, reduced tissue injury in the liver and intestine, as well as complete survival. THC treatment reduced the expansion of donor-derived effector T cells and blocked the killing of host-derived immune cells while promoting Foxp3(+) regulatory T cells. Impaired hematopoiesis seen during GVHD was rescued by treatment with THC. The ability of THC to reduce the clinical GVHD was reversed, at least in part, by administration of cannabinoid receptor (CB) 1 and CB2 antagonists, thereby demonstrating that THC-mediated amelioration of GVHD was cannabinoid receptor-dependent. Our results demonstrate for the first time that targeting cannabinoid receptors may constitute a novel treatment modality against acute GVHD.

An overview of the progress on double umbilical cord blood transplantation

Umbilical cord blood transplantation has been increasingly used over the past years for both malignant and non-malignant hematologic and other diseases as an alternative to mismatched-related or matched-unrelated bone marrow or peripheral blood hematopoietic stem cell transplantation. A disadvantage of cord blood is its low cell content which limits cord blood transplantation to generally low weight recipients, such as children. Various alternatives have been used to overcome this limitation, including co-infusion of two partially HLA-matched cord blood units. According to Eurocord Registry data, this strategy has been applied in approximately 993 adult patients with hematologic diseases since the first double umbilical cord blood transplantation in 1999. In fact, since 2005, the number of adult patients receiving double umbilical cord blood transplantation has surpassed the number of adults transplanted with single cord blood units. The engraftment rate is comparable for both single and double umbilical cord blood transplantation, although the latter is accompanied by a higher incidence of grade II acute graft-versus-host disease and lower leukemia relapse for patients in first complete remission. In the majority of patients undergoing double umbilical cord blood transplantation, transient chimerism, due to the presence of cells from both donor units early post transplant, is replaced by sustained dominance of one unit from which long-term hematopoiesis is derived. Although the biology and the factors that determine unit dominance have not been clarified, the implication of immune-mediated mechanisms has been reported. Preliminary data have demonstrated the safety of double umbilical cord blood transplantation. Ongoing clinical trials and prolonged follow up of the patients will clarify the immunology and determine the efficacy of this approach. We present here a brief overview of the clinical experience on double umbilical cord blood transplantation and its underlying biology.

Novel influenza A (H1N1) 2009 infection in the pediatric patients with hematologic and oncologic diseases in the Yeungnam region

PurposeNatural history and consequences of the novel 2009 influenza A H1N1 (2009 H1N1) infection in immunocompromised pediatric patients are not yet fully understood. In this study, we investigated the clinical features and outcomes of the 2009 H1N1 infection in pediatric patients with hematological and oncological diseases.MethodsWe retrospectively reviewed the medical records of 528 patients who had hematological and oncological diseases and who were treated at 7 referral centers located in the Yeungnam region. Among the 528 patients, 27 with definite diagnosis of 2009 H1N1 infection were the subjects of this study. All patients were divided into the following 3 groups: patients who were receiving chemotherapy (group 1), patients who were immunosuppressed due to a non-malignant hematological disease (group 2), and patients who were off chemotherapy and had undergone their last chemotherapy course within 2 years from the influenza A pandemic (group 3).ResultsAll 28 episodes of 2009 H1N1 infection were treated with the antiviral agent oseltamivir (Tamiflu®), and 20 episodes were treated after hospitalization. Group 1 patients had higher frequencies of lower respiratory tract infection and longer durations of fever and hospitalization as compared to those in group 2. Ultimately, all episodes resolved completely with no complications.ConclusionThese results suggest that early antiviral therapy did not influence the morbidity or mortality of pediatric patients with hematological and oncological diseases in the Yeungnam region of Korea after the 2009 H1N1 infection. However, no definite conclusions can be drawn because of the small sample size.

Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment

Umbilical cord blood (CB) offers an alternative source of hematopoietic stem cells for the treatment of malignant and nonmalignant hematologic diseases. Umbilical CB has high levels of repopulating hematopoietic stem cells and is depleted of immune cells. It elicits low cell dose, and delayed and poor engraftment to the bone marrow. Umbilical CB is used for pediatric transplants as well as in adults. CB transplantation is associated with a high rate of mortality and morbidity, particularly in adults. To improve the success rate, patients are treated with a double CB dose. However, such a strategy limits the availability of CB transplants for patients and the conditions are still suboptimal. Novel avenues are being devised and considered; among them the expansion and propagation of CB stem cells in vitro, and the improvement of homing and engraftment of CB stem cells to the bone marrow. Such strategies would overcome the low cell dose in CB units by improving the delay and engraftment of CB stem cells to t...

Intravenous apoptotic cell infusion as a cell‐based therapy toward improving hematopoietic cell transplantation outcome

Allogeneic hematopoietic cell transplantation (AHCT) is an efficient therapy for different malignant and nonmalignant hematological diseases. However, the use of this therapeutic approach is still limited by some severe toxic side effects, mainly graft-versus-host disease (GvHD). Today, the risk of fatal GvHD restrains the wider application of AHCT to many patients in need of an effective therapy for their high-risk hematologic malignancies. Thus, new strategies, including cell-based therapy approaches, are required. We propose to use intravenous donor apoptotic leukocyte infusion to improve AHCT outcome. In experimental AHCT models, we demonstrated that intravenous apoptotic leukocyte infusion, simultaneously with allogeneic bone marrow grafts, favors hematopoietic engraftment, prevents allo-immunization, and delays acute GvHD onset. Here, we review the different mechanisms and the potential beneficial effects associated with the immunomodulatory properties of apoptotic cells in the AHCT setting.