Allogeneic Peripheral Stem Cell Transplantation Research Articles

Serum microRNA155 is increased in patients with acute graft‐versus‐host disease

To explore the clinical relevance of three lymphocyte-related serum microRNAs (miR-155, miR-214, and miR-326) to the pathogenesis of graft-versus-host disease (GVHD), 64 subjects who received allogeneic peripheral blood stem cell transplantation (allo-PBSCT) were recruited in this study, of whom 19 subjects did not develop GVHD, 25 subjects were diagnosed with acute GVHD (aGVHD), and 20 subjects were diagnosed with chronic GVHD (cGVHD). Serum miRNAs were determined by real-time RT-PCR. Expression level of miRNAs and the expression signatures of miRNAs as a panel were analyzed among the three groups. The expression level of miR-214 and miR-326 showed no significant difference between GVHD and non-GVHD groups. However, miR-155 was significantly up-regulated in GVHD patients. There was a correlation between the level of miR-155 and the severity of aGVHD. Moreover, serum IFN-gamma, IL-17, and IL-9 levels were higher in aGVHD patients with high miR-155. In conclusion, the expression level of lymphocyte-related miR-155 in serum was significantly increased in aGVHD patients. The miR-155 may be considered as a potential targeted therapy for aGVHD patients.

Reduced Intensity Fludarabine and Intravenous Busulfan (FB2) for Allogeneic Peripheral Blood Stem Cell Transplantation

Reduced Intensity Fludarabine and Intravenous Busulfan (FB2) for Allogeneic Peripheral Blood Stem Cell Transplantation

Post-Transplantation B Cell Activating Factor and B Cell Recovery before Onset of Chronic Graft-versus-Host Disease

Excessive levels of B cell activating factor (BAFF) are found in patients with active chronic graft-versus-host disease (cGVHD). In mice, BAFF has been shown to be essential for B cell recovery after myeloablation. To assess how BAFF levels relate to transplantation factors and subsequent development of cGVHD, we prospectively monitored 412 patients in the first year after allogeneic peripheral blood or bone marrow hematopoietic stem cell transplantation (HSCT) and censored data at time of cGVHD onset. In patients who did not develop cGVHD, we affirmed a temporal pattern of gradually decreasing BAFF levels as B cell numbers increase after myeloablative conditioning. In contrast, after reduced-intensity conditioning, BAFF levels remained high throughout the first post-HSCT year, suggesting that the degree of myeloablation resulted in delayed B cell recovery associated with persistence of higher BAFF levels. Given that high BAFF/B cell ratios have been associated with active cGVHD, we examined differences in early BAFF/B cell ratios and found significantly different BAFF/B cell ratios at 3 months post-HSCT only after myeloablative conditioning in patients who subsequently developed cGVHD. In addition to HSCT conditioning type, the use of sirolimus was significantly associated with higher BAFF levels after HSCT, and this also was potentially related to lower B cell numbers. Taken together, our results are important for interpreting BAFF measurements in cGVHD biomarker studies.

Toxic epidermal necrolysis due to voriconazole: case report and review

Toxic epidermal necrolysis is an uncommon but potentially life-threatening adverse cutaneous drug reaction characterized by variable degrees of epidermal necrosis and detachment leading to morbidity and risk of mortality. We describe a 67-year-old woman who underwent allogeneic peripheral blood stem cell transplantation as treatment for chronic lymphocytic leukemia. She developed toxic epidermal necrolysis after she was transitioned to voriconazole, which was a component of her post-transplant regimen. The diagnosis of toxic epidermal necrolysis in our patient was made clinically and confirmed histologically. Based on the temporal initiation of voriconazole therapy and the development of her adverse cutaneous reaction, we concluded that voriconazole was the offending agent. There are limited reported cases of voriconazole-induced toxic epidermal necrolysis; we report this case to increase awareness of this potential life-threatening complication.

Allogeneic peripheral blood stem cell transplantation for an acute myeloid leukemia patient with a rare Rh-variant D-- phenotype

We here report a rare case of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for an acute myeloid leukemia (AML) patient with the Rh-variant D phenotype. People whose red blood cells (RBCs) have a rare deleted Rh phenotype (D ) readily produce anti-Rh17 alloantibodies (an antibody to the RhCc/Ee protein). This causes clinical complications resulting from RBC destruction due to the interaction of alloantibodies with RBCs carrying the corresponding antigen. Consequently, patients with such variants who have formed alloantibodies pose a challenge for transfusions given the scarcity of compatible donors. In fact, in Japan, only 1 in 200,000 individuals are eligible donors. A 26-year-old male AML patient underwent allo-PBSCT from an HLA-matched sibling donor. He had the rare D phenotype and developed anti-Rh17 alloantibodies before allo-PBSCT. Given the scarcity of compatible blood donors for transfusions, the patient required autologous blood donations in preparation for allo-PBSCT. RBC engraftment was prompt during allo-PBSCT; thus, no unscheduled RBC blood transfusion was required. Five months later, his blood type changed to that of his sibling donor, and no irregular antibodies to RBCs were detected. (Journal of Hematopoietic Cell Transplantation 3(3): 93-96, 2014.)

Successful treatment of myelodysplastic syndrome and Behcet colitis after allogeneic hematopoietic stem cell transplantation

Successful treatment of myelodysplastic syndrome and Behcet colitis after allogeneic hematopoietic stem cell transplantation

Status Epilepticus Due to Severe HHV-6 Encephalitis in an Allogeneic Stem Cell Transplant Recipient

Reactivation of human herpes virus-6 (HHV-6) after stem cell transplantation occurs frequently. It is associated with clinical manifestations varying from nonspecific symptoms such as fevers or rash, to severe life threatening complications including post-transplantation limbic encephalitis. We report a case of severe HHV-6 encephalitis with viremia in an allogeneic peripheral stem cell transplant recipient who presented with status epilepticus unresponsive to antiepileptic therapy. With intravenous ganciclovir and supportive care, the patient’s condition improved. Awareness of HHV-6 infection in stem cell transplant recipients may help with early diagnosis and improved outcome.

Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic mobilization peripheral blood stem cell transplantation.

Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. After one month, bone marrow biopsy and aspiration confirmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. The patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia.

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Introduction: ICU acquired weakness (ICUAW) is defined as a presence of muscle wasting and neuromuscular dysfunction in critically ill patients without plausible etiology. ICUAW is associated with increased mortality, prolonged mechanical ventilation, and impaired post ICU independent life. Bioelectrical impedance analysis (BIA) is an easy, noninvasive method of estimating body composition using different electrical impedance of tissue components. We have attempted to investigate correlation between serial BIA tests and muscle power examinations in the ICUAW case. A 39-year old patient with a history of acute myeloid leukemia on a remission state after chemotherapy and allogeneic peripheral blood stem cell transplantation, was admitted with general weakness and immobilization due to thoracic spine compression fracture. Respiratory failure with hypoxemia and hypercapnia was developed due to hospital acquired pneumonia on the right lower lobe and recurrent left pneumothorax. He was transferred to medical ICU and mechanical ventilator was applied. Chest tube was inserted and intravenous antibiotics were administered. After proper management for 2 weeks, He was recovered from pneumonia and pneumothorax, but muscle power became weakened and atrophy progressed during the ICU stay. He was not able to sit on a bed for himself. Weaning from mechanical ventilator had failed, tracheostomy was done and BIPAP was applied instead. Muscle power grades of all extremities at ICU admission were IV. At 9th day of ICU stay, the motor power of shoulder abduction, adduction of right and left was IV/IV-, IV/IV-, elbow flexion and extension IV-/IV-, IV/IV, wrist flexion and extension, hand grip were all IV on medical research council (MRC) scale. The motor power of hip flexion, extension was III/IV-, III/IV, Knee flexion, extension IV-/ IV-, IV/ IV, ankle dorsiflexion, plantar flexion III/IV, III/IV. Considering the weakness was developed after the onset of pneumonia, generalized involving both proximal and distal muscles, MRC sum score below 48, and dependency on mechanical ventilation, the diagnosis was compatible with ICUAW. The BIA results of skeletal muscle mass (SMM) and Fat free mass (FFM, listed in brackets) was 16kg (32.1kg) at 3rd day of ICU stay, continuous declined to 14.6kg (30.1kg) at 9th day of ICU stay. Appendicular muscle mass of right arm, left arm, right leg and left leg at 3rd day after ICU admission were 0.8, 0.9, 6.2, 6.5kg each. After 9th day of ICU admission, both lower extremities muscle mass decreased from to 6.2kg to 5.0kg at right side and 6.5kg to 5.2kg at left side. Passive range of motion of each joint was maintained during the ICU stay to prevent joint contracture. Physical therapy including range of motion against resistance (RROM) with cycle ergometer and sitting to chair exercise was started at 22th day after ICU admission. After two weeks of physical therapy, the muscle strength of extremities was slightly improved before physical therapy from grade IV- to IV+ in both shoulder adduction and abduction, IV-to IV in right elbow flexion and hip extension, IV to IV+ in right wrist flexion, III to IV- in both ankle dorsiflexion compared with the result of muscle power examination at 9th day. Total SMM and FFM slightly increased from 14.6 to 15.0 and 30.1 to 30.7kg. Appendicular muscle mass of right arm, left arm, right leg and left leg increased from 1.0, 0.9, 5.0, 5.2 to 1.2, 1.0, 5.6, 5.5kg. The change of truncal muscle mass was not correlated with that of partial pressure of arterial CO2 or ventilatory parameters. As a medical condition of the patient was fluctuating, the clinical muscle power after a month was not improved and so was the BIA result. The changes of total skeletal and appendicular muscle mass were proportional to the clinically detected muscle strength. Based on the result, further study is planned to determine whether the BIA could predict occurence and clinical course of ICUAW using variable BIA parameters.

Recurrent cardiac chloroma presenting as acute chest pain

### Learning Point for Clinicians Granulocytic sarcoma should be a part of the differential diagnosis of patients who present with mass lesions after allogeneic transplant for chronic myeloid leukemia, even in the absence of hematologic relapse. A 41-year-old man presented to the hospital with sudden onset of chest tightness. His past medical history was notable for diagnosis of chronic myeloid leukemia (CML), made at 33 years. He was treated with imatinib, dasatinib and allogeneic peripheral blood stem cell transplant (PBSCT) with HLA mismatched, unrelated donor and he was still in complete hematologic response. On admission, his vital signs and cardiac enzymes were normal. Right ventricular hypertrophy was newly developed compared with his previous electrocardiography. He got an urgent coronary angiography due to ongoing chest pain, and the result showed no significant stenosis but anomalous tumor feeding vessels from left circumflex artery. A huge branch of left circumflex artery was supplying …

Significant improvement following combination treatment with mefloquine and mirtazapine in a patient with progressive multifocal leukoencephalopathy after allogeneic peripheral blood stem cell transplantation

We report a case of a 40-year-old female who developed progressive multifocal leukoencephalopathy (PML), which is associated with JC virus reactivation, after allogeneic hematopoietic cell transplantation. As she had been suffering from graft-versus-host disease and lung damage after pneumocystis pneumonia, the administration of calcineurin inhibitor and steroid could not be discontinued. However, she showed a favorable improvement in clinical symptoms and imaging findings after treatment with the anti-malarial drug, mefloquine and a serotonin receptor blocker, mirtazapine. Continuation of the treatment for eight months finally led to the clearance of the JC virus from her cerebrospinal fluid. She currently shows no neurological disturbance and has resumed her daily activities. PML due to the severe immunosuppressive condition has been reported as a fatal complication after allo-SCT. Our case suggests that combination treatment with mefloquine and mirtazapine may be of great value for the treatment for PML patients in the post allo-SCT setting, although it is difficult to say whether the combination treatment alone led to improvement. Further clinical study is needed to clarify the efficacy of these drugs for the treatment of PML.

Lung Parenchyma–Derived IL-6 Induces Alloantigen Specific Th17 Differentiation Within The Lung and Idiopathic Pneumonia Syndrome After Allogeneic Stem Cell Transplantation

Idiopathic Pneumonia Syndrome (IPS) is a fulminant and largely untreatable form of GVHD of the lung following allogeneic stem cell transplantation (SCT). It characteristically develops in the third week after SCT in patients receiving prior total body irradiation (TBI). We have previously shown that IFNγ signaling within lung parenchyma is critical for preventing disease (Burman AC et al, Blood 2007, 110:1064). Using IL-17A-fate reporter grafts (where YFP is expressed if a T cell has ever made IL-17) we now show that Th17 cells preferentially accumulate in the lung (but not other sites) after experimental allo-SCT in recipients in which IFNγ is neutralized (lung Th17 cells: 6.6x104 ± 0.2 vs. 0.8x104 ± 0.01, anti-IFNγ vs. control treated, P = 0.002). To understand whether this accumulation of Th17 cells in the lung and IPS in general was an alloreactive (i.e. GVHD) dependent phenomena, we transplanted luciferase expressing B6 TEa TCR transgenic CD4+ T cells specific for alloantigen (I-Ed) expressed in B6D2F1 recipients in the presence or absence of IFNγ neutralization. Remarkably, allospecific donor TEa T cells again accumulated in the lung in the absence of IFNγ (BLI: 2.2x105 ± 0.6 vs. 0.54x105 ± 0.08 ph/sec/cm2/sr, P = 0.008), but not other sites, excluding responses to other antigens (e.g. pathogen-derived) as a cause for IPS. Critically, we show that donor T cell-derived IFNγ was vital for inhibiting IL-6, TGFβ and IL-21 mRNA expression in lung parenchymal cells after SCT. Protein analysis confirmed that IL-6 was markedly elevated in lung tissue lysate 5 days after allo-SCT in IFNγR–/– recipients compared to WT (128 ± 25 pg/ml vs. 20 ± 5 pg/ml, P = 0.002). In contrast, IL-6 was elevated to equivalent levels in sera of both WT and IFNγR–/– SCT recipients. Studies using IL-6–/– recipients demonstrated that IL-6 was critical for Th17 differentiation within the lung and subsequent IPS. In the absence of IFNγ, IL-6 promoted Th17 cells to preferentially expand in the lungs (14.6x104 ± 0.03 vs. 3.8x104 ± 0.01, WT vs. IL-6–/–, P = 0.04), produce IL-17A (3734 ± 736 pg/ml vs. 521 ± 142 pg/ml, WT vs. IL-6–/–, P = 0.003) and induce IPS (lung pathology scores: 7.3 ± 0.9 vs. 5.0 ± 0.3, WT vs. IL-6–/–; P = 0.02). Consistent with Th17 differentiation as the final pathological pathway, systemic blockade of IL-17A or the transplantation of grafts lacking the IL-17 receptor also profoundly attenuated disease (lung pathology scores: 3.9 ± 0.5 vs. 6.7 ± 0.6, anti-IL-17A vs. control treated, P = 0.002; and 4.5 ± 0.4 vs. 8.1 ± 1.0, IL-17RA–/–- vs. WT, P= 0.003, respectively). Thus IFNγ is the critical cytokine for suppressing an environment conducive to Th17 differentiation within the lung and IPS after allogeneic SCT.To study the clinical relevance of these findings we examined IL-6 dysregulation in a cohort of patients receiving allogeneic peripheral blood stem cell transplantation at our institution. We confirm that plasma levels of IL-6 are also significantly elevated in SCT recipients within the first 2 weeks of transplantation (30.6 ± 8.8 pg/ml vs. 8.3 ± 3.5 pg/ml, day +7 vs. day -7, P = 0.008), particularly in patients receiving Cy/TBI (12 Gy) compared to reduced intensity Flu/Mel (120mg/m2) conditioning (74.4 ± 38.4 pg/ml vs. 23.4 ± 7.1 pg/ml, P = 0.04). Furthermore, standard calcineurin and methotrexate–based immune suppression completely prevented systemic IFNγ generation after SCT, thus inducing an IL-6–high, IFNγ–deplete environment highly conducive to the development of IPS. These data confirm IL-6 and IL-17 as logical therapeutic targets to prevent IPS after clinical SCT utilizing TBI-based conditioning. Disclosures:No relevant conflicts of interest to declare.

Granulocyte Colony-Stimulating Factor Mobilization Affects The Expression Of Regulatory γδ T Cells

BackgroundThe immune modulatory effect of granulocyte colony-stimulating factor (G-CSF) on T cells resulted in an unexpected low incidence of graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation. Our previous studies demonstrated that G-CSF mobilization influenced the distribution and clonality of TRGV and TRDV repertoire (T cell receptors of γδ T cells), and significant positive correlation was observed between the invariable clonality of TRDV1 gene repertoire after G-CSF mobilization and low incidence of GVHD in recipients (P=0.015, OR=0.047) (Li Xuan et al. Journal of Translational Medicine 2011). Regulatory γδ T cells (γδ Tregs), which express Foxp3 and primarily belong to CD27+CD25high phenotype, are a novel subset of cells with immunosuppressive function (Xiaoyan Li et al. Journal of Immunology 2012). However, whether G-CSF could influence the expression of γδ Tregs remains unknown. The aim of this study was to investigate the effect of G-CSF mobilization on the expression of γδ Tregs. MethodsThe immunophenotyping of γδ Tregs was analyzed in peripheral blood mononuclear cells (PBMCs) from 20 donors before and after G-CSF mobilization, using flow cytometry. ResultsCompared with that before mobilization, the proportions of Vδ1 and CD25+ subsets were significantly increased (P=0.012, P=0.032), whereas the Vδ2 proportion was significantly decreased after G-CSF mobilization (P=0.002). The proportions of total γδ T cells, CD27+ and Foxp3+ subsets were similar between the two groups (P=0.133, P=0.110, P=0.780, respectively). In addition, there was a significant increase in the proportions of Foxp3+Vδ1 and CD25+Foxp3+ subsets (P=0.038, P=0.013), and a significant decrease in the proportions of CD27+Vδ2 and CD25+Vδ2 subsets after G-CSF mobilization (P=0.013, P=0.022). The proportions of CD27+γδ T, CD25+γδ T, Foxp3+γδ T, CD25+CD27+, CD27+Foxp3+, CD27+Vδ1, CD25+Vδ1 and Foxp3+Vδ2 subsets were similar before and after G-CSF mobilization (P=0.422, P=0.342, P=0.724, P=0.070, P=0.503, P=0.053, P=0.386 and P=0.097, respectively). We then compared the Foxp3, CD27 and CD25 phenotypes in total γδ T cells, Vδ1 and Vδ2 subsets. We observed a significant increase in the proportion of CD27+Foxp3+ Vδ1 subsets after G-CSF mobilization (P=0.036). The proportion of CD27+Foxp3+γδ T and CD27+Foxp3+Vδ2 subsets before mobilization were similar to that after mobilization (P=0.539, P=0.507). The proportion of CD25+Foxp3+γδ T, CD25+Foxp3+ Vδ1, CD25+Foxp3+Vδ2, CD25+CD27+γδT, CD25+CD27+Vδ1 and CD25+CD27+ Vδ2 subsets were also similar between the two groups (P=0.249, P=0.539, P=0.507, P=0.934, P=0.209 and P=0.061, respectively). ConclusionsG-CSF mobilization significantly increased the proportions of Vδ1 subsets, including Foxp3+Vδ1 and CD27+Foxp3+ Vδ1 subsets, whereas decreased the Vδ2 proportion. Disclosures:Li:This work was supported by Grants from National Natural Science Foundation of China (30871091 and 91129720), the Collaborated grant for HK-Macao-TW of Ministry of Science and Technology (2012DFH30060), the Guangdong Science & Technology Project (2012B0506: Research Funding. Liu: It was supported by 863 Program (No. 2011AA020105).: Research Funding; It was supported by National Public Health Grand Research Foundation (Grant No. 201202017), National Natural Science Foundation of China (Grant No.81000231, No.81270647).: Research Funding; It was supported by Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ≥60 years. In multivariate analysis, the donor type/age group and the graft CD34(+) and CD3(+) cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ≥60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34(+) cell dose more than 4.5×10(6)/kg (HR: 0.56; P=0.002) and CD3(+) cell dose more than 3×10(8)/kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an "adapted Disease Risk Index" by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progression-free survival (P=0.04) but not for overall survival (P=0.82).

Allogeneic peripheral blood stem cell transplantation using reduced-intensity conditioning in an outpatient setting in ABO-incompatible patients: are survival and graft-versus-host disease different?

Graft-versus-host disease (GVHD) is a major cause of morbimortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Minor ABO incompatibility has been associated with an increased risk of GVHD. We analyzed the impact of ABO matching on patient outcome after peripheral blood, reduced-intensity allo-HSCT in an outpatient setting, and its relationship with GVHD. Data of 121 patients were included. All patients received allo-HSCT from HLA-identical siblings as outpatients using a reduced-intensity conditioning regimen. Influence of ABO matching as a risk factor for the development of GVHD and survival was analyzed using logistic regression and Cox proportional hazards regression, respectively. Median age was 36 years (range, 1-71 years); 88 patients were ABO identical: 13 presented major mismatch and 20 minor mismatch, with an ABO incompatibility rate of 27.3%. The median follow-up period was 54 months (range, 0.3-120 months). Minor ABO incompatibility patients presented the highest rate of acute GVHD (aGVHD; 25%), in comparison with ABO-identical (20.5%) and major ABO incompatibility patients (15.4%; p = 0.79). The highest incidence of chronic GVHD (cGVHD) occurred in the context of minor ABO incompatibility (35%), in contrast to ABO-identical (30.8%) and major ABO incompatibility (15.4%). Survival was higher for patients in the minor ABO mismatch group; however, there was no significant correlation between ABO matching status and survival (p = 0.45). Using this type of peripheral blood stem cell transplantation, minor ABO-mismatched allo-HSCT was associated with a higher incidence of aGVHD and cGVHD and with increased survival, albeit with no significance.

Comparison of Unrelated Cord Blood Transplantation and HLA-Matched Sibling Hematopoietic Stem Cell Transplantation for Patients with Chronic Myeloid Leukemia in Advanced Stage

This is the first report to present a clinical comparison of unrelated cord blood transplantation (CBT) and HLA-matched sibling allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia (CML) in advanced stage (accelerated phase or blast crisis). A total of 32 consecutive patients with advanced CML received unrelated CBT (n = 16) or HLA-matched sibling allogeneic peripheral blood stem cell or bone marrow transplantation (allo-PBSCT/BMT) (n = 16) between 2002 and 2011. The median day to neutrophil engraftment and the median day to platelet engraftment were longer in the unrelated CBT group. The cumulative incidence of grades 1 to 2 acute graft-versus-host disease (aGVHD), grades 3 to 4 aGVHD, and chronic graft-versus-host disease did not differ significantly between the 2 cohorts. The cumulative incidence of transplantation-related mortality (TRM) at day +180 was higher in CBT group (37.5% versus 12.5%, P = .013). The risk of relapse was lower in CBT patients compared with that of allo-PBSCT/BMT patients (14.2% versus 42.7%, P = .03). The long-term survival in CBT group patients was slightly better than that of allo-PBSCT/BMT group, although the difference did not reach statistical significance: the 5-year overall survival for CBT patients and allo-PBSCT/BMT patients was 62.5% and 48.6%, respectively (P = .10), whereas the 5-year leukemia-free-survival rate was 50% and 40.5%, respectively (P = .12). Our comparisons suggest that patients with advanced CML receiving unrelated CBT had a lower relapse rate, a slightly better long-term survival, but a higher early TRM than those receiving HLA-matched related allo-PBSCT/BMT.

Risk Factors and Predictors of Severity Score and Complications of Pediatric Hemorrhagic Cystitis

We retrospectively analyzed our institutional incidence of hemorrhagic cystitis, identified risk factors, and examined associations of risk factors with disease severity and genitourinary complication rates. We reviewed charts of all consecutive pediatric patients treated from 1986 to 2010. We analyzed demographics, underlying diagnosis and treatment data to assess risk factors for hemorrhagic cystitis. We also correlated disease severity scores with clinical predisposing factors, and performed univariate and multivariate analyses to examine associations between risk factors and outcomes. Hemorrhagic cystitis was observed in 97 of 6,119 children (1.6%), most of whom (75%) had severity scores of II or III. Mean ± SD age was 12.2 ± 6.3 years for patients with hemorrhagic cystitis and 10.5 ± 7 years for patients without hemorrhagic cystitis (p = 0.017). On univariate analysis increased risk of hemorrhagic cystitis was significantly associated with age greater than 5 years, male gender, cyclophosphamide or busulfan chemotherapy, bone marrow or peripheral blood stem cell transplantation, pelvic radiotherapy and underlying diagnoses of rhabdomyosarcoma, acute leukemia and aplastic anemia. On multivariate analysis age greater than 5 years, allogeneic bone marrow or peripheral blood stem cell transplantation and pelvic radiotherapy were significantly associated with increased risk of hemorrhagic cystitis. Older age, late onset hemorrhagic cystitis, positive urine culture for BK virus and bone marrow or peripheral blood stem cell transplantation were associated with greater disease severity. Patients with higher severity scores more frequently experienced bladder perforation, hydronephrosis, overall hemorrhagic cystitis complications, and increased creatinine and blood urea nitrogen levels during followup. Older age, previous bone marrow or peripheral blood stem cell transplantation and BK virus in the urine are risk factors for hemorrhagic cystitis and are associated with a higher severity score. Higher severity scores are associated with increased rates of genitourinary complications and renal impairment.

Predictive factors for rapid neutrophil and platelet engraftment after allogenic peripheral blood stem cell transplantation in patients with acute leukemia

The aim of this study was to investigate predictive factors for rapid engraftment after allogeneic peripheral blood stem cell transplantation (alloPBSCT) in patients with acute leukemia. Two hundred sixty-two patients receiving alloPBSCT were analyzed. Subset analyses of donor stem cells were conducted using a flow cytometric method. The correlation between rapid engraftment of neutrophils, platelets, and donor stem cells doses, as well as other recipient and donor clinical factors, was analyzed. In univariate analysis, factors correlated with neutrophil engraftment (≥0.5 × 10(9)/L) by day 12 were achievement of complete remission (CR) after induction chemotherapy (CR1) before hematopoietic cell transplantation (HCT) and high numbers of CD34+ cells, CD3+ T cells, and CD3+/CD4+ T cells. Factors correlated with platelet engraftment (≥20 × 10(9)/L) by day 12 were achievement of CR1 before HCT, donor and recipient sex mismatch, and high numbers of mononuclear cells, CD34+ cells, CD3+ T cells, CD3+/CD4+ T cells, CD3+/CD8+ T cells, and CD56+ NK cells. In multivariate analysis, independent predictive factors for rapid neutrophil and platelet engraftment were CR1 before HCT (p < 0.001 and p = 0.002, respectively), high number of donor CD34+ cells (p = 0.005 and p < 0.001, respectively), and high number of CD3+ T cells (p = 0.005 and p = 0.001, respectively). In conclusion, achieving CR1 before HCT, as well as larger quantities of donor CD34+ and CD3+ T cells, may predict rapid neutrophil and platelet engraftment after PBSCT.

Oral High Dose Dexamethasone for Pure Red Cell Aplasia Following ABO-Mismatched Allogeneic Peripheral Blood Stem Cell Transplantation: A Case Report.

Management of pure red cell aplasia following major ABO-mismatched hematopoietic stem cell transplantation is a therapeutic challenge. Various therapeutic modalities have been tried with variable responses, and patient remains transfusion dependent for a long time. We report here the use of pulsed oral high dose dexamethasone for pure red cell aplasia following ABO-mismatched allogeneic transplant with complete recovery.

Lack of association of platelet-derived growth factor (PDGF) receptor autoantibodies and severity of chronic graft-versus-host disease (GvHD)

The existence of platelet-derived growth factor (PDGF) receptor autoantibodies in systemic sclerosis is conflicting, and such antibodies were also detected in patients with chronic graft-versus-host disease (GvHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). We therefore aimed to screen for PDGF receptor autoantibodies in patients with chronic GvHD. We evaluated the existence of PDGF receptor autoantibodies in 39 patients, while 17 patients presented with a limited and 8 patients with an extensive chronic GvHD, respectively. Furthermore, 14 out of 39 patients had no chronic GvHD. We detected at least low levels of PDGF receptor autoantibodies in nearly all (35 of 39) patients after allogeneic PBSCT. Interestingly, only one of six patients with high levels of PDGF receptor autoantibodies presented with an extensive chronic GvHD, while the remaining six patients had no clinical signs of chronic GvHD. Thus, there was no correlation between the quantitative detection of antibodies directed against the PDGF receptor and the presence or severity of chronic GvHD. Platelet-derived growth factor receptor autoantibodies could easily be detected in patient sera. Nevertheless, we did not observe any correlation between the presence of PDGF receptor autoantibodies and the severity of chronic GvHD in patients who underwent allogeneic PBSCT.