Allogeneic Peripheral Stem Cell Transplantation Research Articles

Anti-MDA5 antibody-positive rapidly progressive interstitial lung disease after allogeneic hematopoietic cell transplantation successfully treated with triple immunosuppressive therapy

A 34-year-old man with KMT2A-MLLT1 acute myeloid leukemia in first complete remission underwent allogeneic peripheral blood stem cell transplantation from his HLA-matched sister after conditioning with busulfan/cyclophosphamide. He did not have severe graft-versus-host disease, but he developed interstitial pneumonia six months after transplantation when his oral cyclosporine A (CsA) dose was reduced to 10 mg/day. He was given prednisolone (PSL), which temporarily improved his respiratory condition, but he quickly deteriorated when PSL was reduced. Anti-MDA5 antibody was found to be positive after additional testing, and a three-drug combination of intravenous cyclophosphamide+PSL+CsA was initiated for anti-MDA5 antibody positive rapidly progressive interstitial lung disease, which was effective for interstitial pneumonia. He received a successful living-donor lung transplant from his younger brother and sister. We present a case of rapidly progressive anti-MDA5 antibody positive interstitial lung disease in which the patient's respiratory condition improved after triple therapy and subsequent living-donor lung transplantation.

The effect of granulocyte colony stimulating factor on genotoxicity in allogeneic peripheral blood stem cell transplantation donors: a prospective case-control study.

Every year, thousands of donors are exposed to granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization in hematopoietic stem cell transplantations (HSCT). Previous studies about the genotoxicity of G-CSF were inconclusive. In this study, the genotoxic effects of G-CSF in peripheral blood stem cell (PBSC) donors were evaluated prospectively by using three different validated and reliable methods for the first time in the literature to the best of our knowledge. Donors of PBSC transplantation (n=36), who received G-CSF were evaluated for genotoxicity by micronucleus test (MNT), nuclear division index (NDI), and comet assay (CA). Genotoxic effects are expected to cause an increase in MNT and CA values and decrease in NDI. Blood samples were collected at three timepoints (TP): before starting G-CSF (TP1), after G-CSF for five days (TP2), and one month after the last dose (TP3). Sixteen controls were included for baseline comparison of genotoxicity tests. CD34 cell counts and hemograms were also analyzed. MNT and CA parameters; comet and tail length, tail DNA%, and tail moment, showed no change in time whereas another CA parameter, Olive`s tail moment (OTM) was increased significantly at TP3 compared to both baseline and TP2 (p=0.002 and p=0.017, respectively). Nuclear division index decreased significantly at TP2 (p < 0.001), then increased above baseline at TP3 (p=0.004). Baseline comparison with controls showed higher MN frequency in donors without statistical significance (p=0.059). Whereas, CA results were significantly higher in controls. CD34 cell count showed moderate positive correlation with white blood cell count at TP2 (Pearson R=0.495, p=0.004). Our results showed the genotoxic effect of G-CSF in healthy donors, in two of the three tests performed, short-term effect in NDI, and long-lasting effect in OTM. So, this study provides novel information for the debate about the genotoxicity of G-CSF and supports the need for further studies with a larger sample size and longer follow-up.

Addition of Ruxolitinb to Corticosteroids As First-Line Therapy for High-Risk Acute Graft Versus Host Disease in Allogeneic Peripheral Blood Stem Cell Transplantation

PURPOSE Corticosteroids (2mg/kg/day) are commonly used as first-line treatment for acute graft versus host disease(aGVHD). However, steroid is effective in only about half of patients. Based on the promising efficacy of ruxolitinib as second-line therapy for aGVHD, we performed a randomized controlled study to assess the safety and efficacy of corticosteroids (2mg/kg/day) alone versus ruxolitinb combined with reduced dose of corticosteroids (1mg/kg/day) in patients with high-risk aGVHD after allogeneic peripheral blood stem cell transplantation. METHODS This multicenter, randomized, phase II controlled study (ClinicalTrials.gov, NCT04061876) enrolled patients with newly diagnosed aGVHD from 7 Chinese centers. Patients were randomly assigned at a ratio of 1:1 to methylprednisolone (2mg/kg/day) alone (steroids group) or ruxolitinib (5 mg/day) combined with methylprednisolone (1 mg/kg/day) (RUX/steroids combined group). The primary endpoint is the overall response rate on day 28, which is defined as an improvement of at least one stage in the severity of aGVHD in one organ without deterioration in any other organ or disappearance of any GVHD signs from all organs without requiring new systemic immunosuppressive treatment. The secondary objectives consist of response time, response duration, overall survival, disease-free survival, non-relapse mortality, failure-free survival. RESULTS From August 25 of 2019 to June 1 of 2022, 198 patients were enrolled and evaluated for response with a median follow-up of 601 days (Figure 1). The overall response rates at day 28 were 92.9% in the RUX/steroids combined group and 70.7% in the steroids group, respectively (P = 0.002; Figure 2A). Durable overall response at day 56 was significantly higher in the RUX/steroids combination group than in the steroids alone group (86% vs. 46%; odds ratio,7.69; P <0.001; Figure 2B) The incidences of adverse events were comparable between these two groups. For both groups, the most common grade 3 or worse adverse events were anaemia, thrombocytopenia and gamma-glutamyltransferase increased that were self-limiting. CONCLUSION Addition of ruxolitinb (5 mg/day) to methylprednisolone (1 mg/kg/day) represents an effective first-line therapy for newly diagnosed acute GVHD, which resulted in a high overall response rate and is well tolerated. These findings are an important contribution to the field, showing a safe strategy to incorporate ruxolitinb (5 mg/d) into the standard first line regimen for newly diagnosed acute GVHD internationally. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Time-Series Reconstruction of CBC Profile of Pediatric Cancer Patients for Two Years after Hematopoietic Stem Cell Transplantation Using Language Programming

In this single center and retrospective study, we analyzed every single patient totaling 249 patients who was admitted and undergone hematopoietic stem cell transplantation (HSCT) at our institution from year 2013 to 2019. Twenty three patients were excluded mainly due to returning home country after HSCT without further follow up at our institution. We re-analyzed the remaining 226 patients (169 alive patients and 57 expired patients) and re-constructed time-series laboratory data of white blood cell (WBC) count (Figure 1), hemoglobin, platelet, absolute neutrophil count (ANC), monocytes number, blood urea nitrogen, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, lactate dehydrogenase (LDH), cyclosporine level, and/or tacrolimus level for up to two years since their last HSCT. These large sets of data were visualized by custom-written codes using language programming. We performed subgroup analysis of these patients' laboratory data according to the tumor type, which was grouped into acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), other types of leukemia not aforementioned, lymphoma, solid tumor, aplastic anemia and other diseases including neurologic disease or immunodeficiency. We also compared these patients' laboratory data according to immunosuppressant used (cyclosporine versus tacrolimus), and hematopoietic stem cell transplantation procedures employed (allogeneic peripheral blood stem cell transplantation (PBSCT), autologous PBSCT or bone-marrow transplantation). In all patients analyzed who remain alive after HSCT (male 100 patients (59%), female 69 patients (41%), the median WBC engraftment time was 13 days with interquartile range (IQR) of 11-15 days). Both WBC and ANC steadily increased after engraftment up to 400 days since HSCT and reached plateau level at 7,000cells/uL for WBC and 3,000cells/uL for ANC. Hemoglobin and platelet showed faster recovery time since HSCT as hemoglobin level of 12 g/dL and platelet count of 200x10^9/L both reached at 300 days since HSCT. Patients underwent HSCT due to the occurrence of solid tumor generally showed shorter WBC engraftment time of 11 days with IQR of 10-12 days while those with hematologic malignancy showed relatively longer WBC engraftment time of 14 days with IQR of 12-16 days. In subgroup analysis of hematologic malignancy categorized into ALL, AML, other leukemia not aforementioned and lymphoma, no significant differences in engraftment time or general trend over two-year time-course of WBC, ANC, hemoglobin and platelet. In sharp contrast, 57 patients who have expired since HSCT showed WBC recovery after engraftment - the median WBC engraftment time was 13 days with IQR of 11-16 days - up to 3,000cells/uL but the WBC count did not increase thereafter in the following two years. The hemoglobin and platelet plateau for these expired patients were markedly lower than those alive as hemoglobin level was maintained around 9 g/dL (Figure 2) and platelet count ranged from 50 to 90x10^9/L since HSCT. HSCT is not the end but the beginning of return to normal daily activities for many patients and vigilant long-term care of these patients is crucial not only for the patients but also for their families. As analogous to Fenton growth chart being used for premature babies and their parents to visually aid their growth progression at outpatient clinic, we aimed at constructing time-series laboratory data of HSCT patients since transplantation to serve as reference curves for HSCT patients at our institution with hope that these reference curves as a visual aid may better assist and assure those patients and their families with successful recovery and for those without successful course, early intervention and further treatment may be better understood and accepted by the patients and their families. Figure 1. Time course of white blood cell count for each patient after HSCT. Each line is color-coded differently and represents a single patient. Red curve is the median of all patients with error bars denoting interquartile range. Shaded area also represents interquartile range. Figure 2. Time course of hemoglobin trend for two years after HSCT. Median average of 169 alive patients' data (red) was compared with that of 57 expired patients (blue). Error bars represent interquartile ranges. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Allogeneic Peripheral Blood Stem Cell Transplantation for Bone Marrow Failure Syndromes Using CD34+-Selected Progenitor Cells Co-Infused with a Reduced Number of Non-Mobilized T-Cells

Background Severe aplastic anemia (SAA) patients who fail immunosuppressive therapy (IST) may be candidates for curative allogeneic hematopoietic stem cell transplantation (HCT). Patients with SAA are often heavily transfused with underlying immune-mediated disease, which increases their risk for graft rejection when bone marrow (BM) is used as a graft source. Peripheral Blood Stem Cell (PBSC) grafts have been associated with better engraftment but at a cost of a higher incidence of graft-versus-host disease (GVHD). We developed a novel protocol combining high numbers of GCSF-mobilized CD34+ peripheral blood stem cells with a BM transplant-equivalent dose of T-cells (collected from donors before GCSF administration) to improve engraftment and decrease the risk of GVHD associated with a conventional, unmanipulated PBSC HCT. Methods In this phase II trial, eligible patients included those age 4-80 years with a diagnosis of SAA or other bone marrow failure (BMF) syndromes with ≥ 9/10 HLA-matched related (sibling/family) donors (MRD) or 10/10 matched unrelated donors (MUD). All patients received conditioning with cyclophosphamide (day -7 to -6), anti-thymocyte globulin (day -5 to -2), and fludarabine (day -5 to -1). For MUD patients, low dose total body irradiation (200 cGy) was added to the regimen on day -1. GVHD prophylaxis included cyclosporin (day -4 until at least day +30) and methotrexate (5 mg/m2 , day +1, +3 and +6). The primary outcome of the study was chronic GVHD at 1 year. Secondary outcomes included mortality, engraftment and chimerism, acute and chronic GVHD, immune reconstitution, and comparisons of MRD vs. MUD patients. Results Thirty-five patients (27 with MRD and 8 with MUD) were transplanted between February 2011 and December 2021. Patients had a median age of 30 (range 6-70) years, 46% were males and 54% were females, including 31 having SAA, 3 with SAA transformed to myelodysplastic syndrome (MDS), and one with MDS; 11 patients also had PNH clone pre-transplant. The median numbers of transplanted CD34+ and CD3+ T-cells were 8 ´ 106 cells/kg and 2 ´ 107 cells/kg, respectively. After HCT transplants, all patients had neutrophil recovery with a median 14 (10-32) days. Except for 2/35 (6%) patients having late graft failure, all other 33 (94%) patients achieved sustained engraftment. Platelet recovery was reached in 29 (83%) patients at a median 19 (13-321) days. A total of 97% of patients achieved >95% donor myeloid chimerism (median 14 days), and 94% of patients achieved >95% donor T-cell chimerism (median 30 days). Reactivation of CMV occurred in 21/29 (72%) patients at risk with none developing CMV disease. Full immune reconstitution occurred for most patients by 1-year post-transplant. With a median follow-up of 5 years, the estimated 200-day survival and overall survival were 89% and 85%, respectively. The cumulative incidence of acute grade II-IV GVHD was 23%, and 1-year chronic GVHD rate was 11%, which was significantly lower than our hypothesis that this regimen would lower the chronic GVHD rate to 50% (P < .001). The subgroups of patients with MRD and MUD were compared (Table 1): patients with MUD showed a slower time to achieve neutrophil recovery (P = .001) and platelet recovery (P = .03), and a slightly high graft failure incidence (2 cases), but most other outcomes were similar, compared to patients with MRD. Conclusion For patients with SAA and other BMF syndromes, transplanting high doses of mobilized CD34+ selected cells from MRD and MUD donors combined with a bone marrow transplant equivalent of non-mobilized donor T-cells (a partially T-cell depleted PBSC transplant) achieves rapid and durable donor engraftment and excellent survival. The cumulative incidence of both acute and chronic GVHD with this regimen was significantly lower than that historically reported with conventional PBSC transplants. Notably, low acute and chronic GVHD rates were also achieved in SAA patients with disease refractory to conventional IST who received a graft from a 10/10 HLA-matched MUD donor, although hematopoietic recovery was slightly delayed compared to recipients of a partially T-cell depleted graft from a MRD donor. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Renal Impairment Adversely Impacts Melphalan-Induced Severe GvHD- and GI Toxicity- Free Survival (MGTFS) in Patients Undergoing Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation

Renal Impairment Adversely Impacts Melphalan-Induced Severe GvHD- and GI Toxicity- Free Survival (MGTFS) in Patients Undergoing Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation

Immune reconstitution and survival of patients after allogeneic hematopoietic stem cell transplantation from older donors.

The impact of donor age on the immune reconstitution of patients with hematological malignancies who underwent hematopoietic cell transplantation (HCT) is unclear. We retrospectively compared the outcomes of 381 patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from 308 donors under 50years of age and 73 donors over 50years of age. IVIG was regularly supplemented for patients in the first 3 months post-HCT. The counts of CD8+CD45RA+ naïve T cells were significantly lower in patients of the older donor group than in the younger donor group in the first year after PBSCT (190.6 cells/μl vs. 239.6 cells/μl, p=.018). Patients in the older donor group had significantly fewer CD19+ B cells on day +270 (123.4 cells/μl vs. 183.5 cells/μl, p=.021) and day +365 (169 cells/μl vs. 271.1 cells/μl, p=.01) after PBSCT. Serum IgA (.76g/L vs. .97g/L, p<.001) and IgM levels (.75g/L vs. 1.04g/L, p<.001) were significantly lower in patients in the older donor group from day +60 to +365 after PBSCT. The EBV reactivation rate within the first 3 months after PBSCT was significantly higher in patients in the older donor group (48.6%vs. 38.3%, p=.034). However, the incidences of CMV reactivation, II-IV acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), 3-year relapse rate, 3-year transplant-related mortality (TRM) and 3-year overall survival (OS) were not significantly different between the two groups. In conclusion, donors ≥50years old were associated with inferior immune reconstitution and higher EBV reactivation in patients after PBSCT, but no change in OS.

High-Dose Busulfan-Fludarabine Conditioning and Low Alveolar Volume as Predictors of Pulmonary Complications after Allogeneic Peripheral Blood Stem Cell Transplantation in Children

This study was conducted to investigate risk factors and predictors of infectious and noninfectious pulmonary complications (PCs) after allogeneic hematopoietic stem cell transplantation in children. We conducted a retrospective analysis of the post-transplantation PCs of 240 patients who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) between 2009 and 2018. Transplantation-related variables, pretransplantation baseline spirometry, body plethysmography, and CO diffusing capacity were analyzed for association with the development of infectious PCs (IPCs) and noninfectious PCs (NIPCs). Compared with the control group, the PC group had statistically significantly lower overall survival (50.6% versus 77.8%; P < .001), higher disease-related mortality (26.6% versus 54.4%; P < .001), and higher nonrelapse mortality (31.6% versus 5.9%; P < .001). A greater number of patients received pretransplantation conditioning with high-dose busulfan (520 mg/m2; Bu 520) and fludarabine (160 mg/m2; Flu 160) in both the IPC and NIPC groups. In the multivariate Cox hazard regression analysis, Bu 520 significantly increased the risk of NIPCs (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.13 to 3.49; P=.016), and Flu 160 was a predictor of IPCs (HR, 1.99; 95% CI, 1.13 to 3.49; P=.016). The Bu 520+Flu 160 regimen was associated with a statistically significant increase in the risk of NIPC (HR, 1.92; 95% CI, 1.09 to 3.37; P=.023). In a multivariate analysis using pretransplantation baseline lung function, alveolar volume (VA) grades 3 and 4 and lung function score (LFS) VA categories III and IV were associated with increased risk for both IPCs and NIPCs. Our data identify receipt of the high-dose Bu-Flu conditioning regimen as an independent risk factor for NIPCs after allo-PBSCT. Impaired CO diffusing capacity before transplantation, especially VA reduction, contributes to the risk of post-transplantation pulmonary complications, and pretransplantation risk can be estimated by grading the degree of insufficiency of VA and LFS VA.

Risk factors and survival of refractory cytomegalovirus reactivation after allogeneic peripheral blood stem cell transplantation

Refractory cytomegalovirus reactivation (RCR) after allo-hematopoietic stem cell transplantation (HSCT) is associated with poor outcomes. Current studies for the risk factors and survival of patients with post-transplantation RCR remain limited. 163 patients with Cytomegalovirus (CMV) reactivation undergoing allo-HSCT in Jiangsu Province hospital from Jan 2013 to Dec 2020 were analyzed retrospectively. Multivariate analysis revealed that highest CMV viremia>1×104copies/mL (hazard ratio [HR] 16.895, 95% confidence interval [CI] 3.394-84.109, P=0.001) and platelet count at Day 90 of more than 87.3×109/L (HR 0.381, 95% CI 0.154-0.945, P=0.037) were independent risk factors affecting RCR. As for prognosis of patients with CMV reactivation, results showed that patients with RCR had higher risk of non-relapse mortality (NRM) (39.5% vs. 22.5%, P=0.045), and RCR was an independent risk factor for NRM (HR 2.216, 95% CI 1.137-4.317, P=0.019). There was no significance between patients with or without RCR in terms of overall survival (OS) (50.7% vs. 55.6%, P=0.281) and relapse-free survival (RFS) (43.6% vs. 52.0%, P=0.179). The landmark analysis showed that patients with RCR had higher NRM (P=0.01), worse OS (P=0.02), and RFS (P =0.01) within 100 days after transplantation. Patients with hemorrhagic cystitis (40.9% vs. 64.5%, P =0.028) and who developed viremia>1×105copies/mL (43.4% vs. 58.4%, P=0.033) were associated with worse OS. Factors such as higher viral load, thrombocytopenia, and ATG used in conditioning therapy increased the incidence of RCR. Patients with RCR had worse NRM, OS, and RFS within 100 days after transplantation.

CT-282 Case Report: Successful Management of Severe Veno-Occlusive Disease after Allogeneic Stem Cell Transplantation Using a Transjugular Intrahepatic Portosystemic Shunt

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (VOD/SOS), of the liver is a complication of allogeneic bone marrow or peripheral stem cell transplantation and is known to be an unpredictable, life-threatening complication with high mortality. We report here a case of a 24-year-old male patient who was diagnosed in 2019 at Gustave Roussy institute with AML. The patient was treated with the AML protocol 3+7 in December 2019 with a complete cytologic response and a positive MRD. Leukemia relapse was observed in September 2020, treated by gemtuzumab ozogomycin and cytarabine with a negative MRD. A successful allogeneic bone marrow transplantation from an HLA-matched pheno-identical related donor was conducted on December 22, 2020, using a myeloablative conditioning regimen. The patient was always controlled by a daily blood test and controlled blood transfusions, and a weekly repeated Doppler ultrasound examination did not indicate a high-risk profile of VOD. However, 12 days post transplant, the patient's condition deteriorated with the appearance of abdominal ascites, weight gain of 6 kg (per base 76 kg), and liver cytolysis with ASAT 72 UI/L, ALAT 86 UI/L, and normal bilirubin. Worsening cytolysis was observed, with ASAT 659 UI/L, ALAT 557 UI/L, and normal bilirubin. A Doppler ultrasound found 5 positive criteria of VOD (hepatomegaly, portal dilation, enlargement of the gall bladder wall, splenomegaly, ascites, decrease in the diameter of the subhepatic veins). Defibrotide was initiated. The patient's condition worsened and was refractory to medical therapy. Transjugular intrahepatic portosystemic shunting (TIPS) was performed 13 days after transplantation without technical complications in any case. The median hepatic venous pressure gradient prior to the procedure was 20 mmHg with a drop to 12 mmHg. An abdominal CT scan showed an under hepatic hematoma with hemorrhagic syndrome. Ascites puncture with abdominal drain installation was done. In summary, following TIPS, the patient showed clinical improvement, and VOD resolved subsequently with a complete remission post allogeneic transplant.

CT-098 Impact of T-Cell Dose on Outcome of T Cell–Replete HLA-Mismatched Allogeneic Peripheral Blood Stem Cell Transplantation

The outcome of allogeneic hematopoietic cell transplantation (HCST) relies on both disease-related factors and transplant-related factors including the conditioning regimen and immunotherapy exploiting the graft-versus-tumor (GVT) effect. CD3+ T cells are the main player in the GVT process, but an increased dose of these cells results in an increased risk of acute graft-versus-host disease (GVHD). We aimed to study whether the T-cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes in our patient population. This is a retrospective chart review study including patients over 18 years of age, diagnosed with AML, ALL, or MDS, who underwent PBSC mismatched allogeneic transplant, including haploidentical, one-antigen mismatched related, or 2-alleles mismatched related transplants at the King Hussein Cancer Center's bone marrow transplant program between January 2010 and December 2020. We calculated the median CD3 cell dose and divided all patients into 2 groups (Low and High dose groups) and then measured the cumulative incidence of acute GVHD, chronic GVHD, and 1- and 2-year overall survival (OS). Thirty-five patients were stratified according to the median CD3+ cell dose into the Low CD3 group, which included 18 (51%) patients with a mean dose of 13.7×107/kg (range: 2.8-19.7), and the High CD3 group, which included 17 (49%) patients with a mean dose of 29.7×107/kg (range: 19.8-93.1) (P-value: 0.000). The cumulative incidence of acute GVHD was 60% (n=12) in the Low CD3 group and 40% (n=8) in the High CD3 group (P-value: 0.24). The cumulative incidence of chronic GVHD was 64% (n=9) in the Low CD3 group and 35% (n=5) in the High CD3 group (P-value: 0.26). The overall survival for the cohort (n=35) at 12 months was 60.9% and reached 49.6% at 24 months. The 12-month OS for the Low and High CD3 groups was 66.7% and 52.9%, respectively. The 24-month OS for the Low and High CD3 groups was 66.7% and 33.1%, respectively (P-value: 0.084). Although the study showed a trend toward better OS in the Low CD3+ dose group, the difference was not statistically significant.

Poster: CT-098 Impact of T-Cell Dose on Outcome of T Cell–Replete HLA-Mismatched Allogeneic Peripheral Blood Stem Cell Transplantation

Poster: CT-098 Impact of T-Cell Dose on Outcome of T Cell–Replete HLA-Mismatched Allogeneic Peripheral Blood Stem Cell Transplantation

Toxic leukoencephalopathy with axonal spheroids caused by chemotherapeutic drugs other than methotrexate

BackgroundThe objective of this report is to share the clinicopathological features of chemotherapy-induced toxic leukoencephalopathy, which is a rare and under-recognized disease, clinically characterized by rapidly progressive cognitive loss that often leads to sudden death.Case presentationA 64-year-old woman and a 63-year-old man, who had both suffered from a rapid deterioration of consciousness, were autopsied under the clinical impressions of either the central nervous system graft versus host disease (CNS-GVHD), infectious encephalitis, or autoimmune encephalitis. Both patients had been treated with multiple chemotherapy regimens, including adriamycin, cytarabine arabinoside, daunorubicin, fludarabine, azacitidine, and allogeneic peripheral blood stem cell transplantation to treat hematological malignancies (acute myelogenous leukemia and myelodysplastic syndrome). Neuropathological findings at autopsy revealed rarefaction and vacuolar changes of the white matter with axonal spheroids, reactive gliosis, and foamy macrophage infiltration, predominantly in the visual pathways of the occipital and temporal lobes. Damaged axons exhibited immunoreactivity to beta-amyloid, consistent with axonopathy. However, there was no lymphocyte infiltration that suggested CNS-GVHD or any type of encephalitis.ConclusionThe neuropathology found in the presented cases had the characteristic features of toxic leukoencephalopathy (chemobrain). Our cases showed that toxic leukoencephalopathy can also be caused by chemotherapy drugs other than methotrexate.

Allogeneic peripheral blood haematopoietic stem cell transplantation for the treatment of dogs with high-grade B-cell lymphoma.

Autologous peripheral blood haematopoietic stem cell transplantation (HCT) cures 33%-40% of dogs with high-grade B-cell lymphoma. We hypothesized, based on human allogeneic bone marrow transplantation literature, that transplanting dogs using canine donor leukocyte-matched CD34+ cells would lead to fewer relapses and increased cure rates. We retrospectively reviewed medical records of dogs diagnosed with high-grade B-cell lymphoma who received an identical allogeneic HCT. A total of 15 dogs transplanted at four facilities were identified. Five of fifteen dogs relapsed before transplant. The mean number of donor CD34+ cells/kg harvested and infused into recipient dogs was 8.0 × 106 /kg (range: 2.08 × 106 /kg-2.9 × 107 /kg). The median disease-free interval and overall survival of all dogs was 1095 days (range: 9-2920 days) and 1115 days (range: 9-2920 days), respectively. Two of five dogs, not in remission at transplant, died in the hospital. The median disease-free interval and overall survival of the remaining three dogs was 25 days (range: 15-250 days) and 1100 days (range: 66-1902 days), respectively. The median disease-free interval and overall survival of the 10 dogs who had not relapsed was 1235 days (range: 19-2920 days) and 1235 days (range: 19-2920 days), respectively. One dog died soon after discharge of presumed gastric-dilatation-volvulus. Eight of nine remaining dogs lived >4yrs post-alloHCT, leading to a cure rate of 89%. Acute graft versus host disease was seen in three dogs. These results suggest that allogeneic HCT can cure ~50% more dogs than those treated with autologous HCT.

Pancreatic atrophy and recovery after allogeneic hematopoietic cell transplantation.

Pancreatic atrophy after allogeneic hematopoietic cell transplantation (HCT) is one of the symptoms associated with chronic graft-versus-host disease (GVHD). Although pancreatic atrophy has been considered to cause exocrine insufficiency and weight loss, it is not yet clear what kinds of recipients can be expected to recover their body weight (BW) or pancreatic thickness. In addition, the effect of pancreatic atrophy on the prognosis has not been clarified. We retrospectively analyzed 170 recipients who received allogeneic bone marrow transplantation or peripheral blood stem cell transplantation, and evaluated them using the CT scan images obtained closest to 1, 2, 3, and 4years after HCT. Fifty-five recipients (32.4%) demonstrated pancreatic atrophy, and 11 (20%) of them recovered their pancreatic thickness. While recipients without pancreatic atrophy gradually recovered their BW (P < 0.001), those with atrophy did not (P = 0.12). Moderate and severe chronic GVHD tended to be slightly more common in the atrophy group (47.3% vs 38.3%), whereas the pancreatic thickness tended to recover in these recipients (30.8% vs 10.3%). HCT from a female donor to a male recipient showed superior pancreatic recovery compared to other donor and recipient sex combinations. Pancreatic atrophy treated as a significantly associated with inferior survival (HR 4.91, P < 0.001) and an increased risk of non-relapse mortality (HR 8.75, P < 0.001). These results suggest that it is important to monitor pancreatic thickness after HCT. Further prospective investigations are warranted to clarify the significance of pancreatic atrophy on clinical outcomes.

339 - Impact of CD34+ Graft Cell Dose on Outcomes after Allogeneic Peripheral Blood Stem Cell Transplantation: A Systemic Review and Meta-Analysis

339 - Impact of CD34+ Graft Cell Dose on Outcomes after Allogeneic Peripheral Blood Stem Cell Transplantation: A Systemic Review and Meta-Analysis

LBA7 - A Case Report of Severe Hemolytic Reaction Secondary to Anti-Jka Treated with Rituximab and Steroids after Allogeneic Peripheral Blood Stem Cell Transplantation

LBA7 - A Case Report of Severe Hemolytic Reaction Secondary to Anti-Jka Treated with Rituximab and Steroids after Allogeneic Peripheral Blood Stem Cell Transplantation

Relapsed acute myeloid leukemia presenting as conjunctival myeloid sarcoma: a case report

BackgroundConjunctival myeloid sarcoma (MS) as an isolated presentation of acute myeloid leukemia (AML) relapse is rare. Here, we report a case of unilateral conjunctival MS revealed as a sign of AML relapse.Case presentationA 50-year-old man with a history of AML in remission visited our clinic presenting with a left conjunctival injection persisting for 1 month. Diffuse subconjunctival thickening with conjunctival vascular engorgement was observed. Ultrasound biomicroscopy revealed a hyper-reflective, thickened conjunctiva in his left eye. During the incisional biopsy, the lesion was strongly attached to the underlying sclera; histopathologic examination revealed infiltration of leukemic blasts. The relapse of AML was confirmed by a successive bone marrow biopsy. The ocular lesion disappeared after allogeneic peripheral blood stem cell transplantation (PBSCT) and concomitant salvage radiotherapy on the left eye. The patient has remained in remission for 3 years after allogeneic PBSCT.ConclusionsIncidental conjunctival lesions can indicate AML relapse in patients treated earlier for AML. An ophthalmologist may have a role in the early detection of AML when a patient presents with an atypical conjunctival lesion.

A retrospective single-center analysis of G-CSF-mobilized donor lymphocyte infusion in hematologic malignancies after unmanipulated allogenic PBSCT.

To explore the efficacy and safety of G-SCF-mobilized donor lymphocyte infusion (DLI) for treatment of relapse of hematologic malignancies after allogeneic peripheral blood stem cell transplantation, we performed a retrospective analysis in a cohort of patients with morphologic (n = 36) or molecular (n = 22) relapse post transplantation. The 3-year post-DLI survival rates for therapeutic and preemptive DLI recipients were 16.7% and 33.3%, respectively. The occurrence of DLI-associated acute graft-versus-host disease predicted longer survival, whereas diagnosis of T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early relapse after transplant (< 6months) predicted shorter survival after therapeutic DLI. Cumulative incidence of progression to hematologic relapse and non-relapse mortality after preemptive DLI were 46.8% and 29.1%, respectively. Active disease prior to transplant and early molecular relapse after transplant (< 4months) were the strongest predictors of non-relapse mortality after preemptive DLI. In conclusion, although therapeutic DLI had limited efficacy against T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early post-transplant relapse, patients who developed DLI-associated acute graft-versus-host disease would benefit from this procedure in the setting of G-SCF-mobilized DLI. Furthermore, preemptive DLI could protect half of patients from hematologic relapse after transplantation with acceptable toxicity.

Value of the Assessment of Interleukin 6 level in Allogenic T-cell Replete Haploidentical peripheral blood haematopioetic stem cell transplantation using post-transplant cyclophosphamide as a predictor for the occurrence of acute Graft versus Host Disease

Value of the Assessment of Interleukin 6 level in Allogenic T-cell Replete Haploidentical peripheral blood haematopioetic stem cell transplantation using post-transplant cyclophosphamide as a predictor for the occurrence of acute Graft versus Host Disease