Peripheral Hematopoietic Stem Cell Transplantation Research Articles

Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT.

IntroductionThis study is to investigate the effect of late-onset hemorrhagic cystitis (LOHC) on progression-free survival (PFS) of patients after haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT).MethodsThis retrospective study enrolled 74 patients with hematological malignancies treated with a myeloablative conditioning regimen and haplo-PBSCT. The effect of LOHC on PFS was studied in terms of HC occurrence, grade, disease type, duration, onset time, gender, and age.ResultsThere were 28 patients with LOHC, and no case was with early-onset HC. The cumulative incidence of LOHC was 37.8% (95% CI: 26.9–48.7%). The 2-year expected PFS of 74 patients and 34 AML patients was not significantly different between LOHC patients and patients without HC (P > 0.05). Among 27 ALL patients, the 2-year expected PFS of LOHC patients was 75%, significantly higher than patients without HC (54.2%) (P < 0.05). The 2-year expected PFSs of patients with mild LOHC and severe LOHC were 69.8 and 77.8%, respectively (P > 0.05). Similarly, the onset time, duration, age, and gender of LOHC patients did not show significant effects on PFS (P > 0.05).ConclusionsAfter haplo-PBSCT, LOHC has a significant effect on the PFS of ALL patients. The HC grade, duration, onset time, gender, and age have no significant effect on PFS.

Age Is Not Important for Autologous Peripheral Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Introduction: High-dose melphalan followed by autologous hematopoietic cell transplantation (auto HSCT) has become the standard procedure for patients with symptomatic multiple myeloma (MM). Retrospective analyses suggest that the benefit of HDT extends to elderly myeloma patients, which is an important finding considering that the median age at diagnosis is 69 years (range: 65-74) for MM in United States, using 2010-2014 US SEER data. The aim of our study was to determine the effect of age on stem cell collection and engraftment in patients with MM.Materyal and Methods: From January 2010 through April 2016, data from 260 myeloma patients below the age of 65 were compared to 41 myeloma patients above 65 years of age who were eligible for auto HSCT according to geriatric assessment (GA), depending on the results of IMWG report in 2015. All these data were obtained from the Ankara University Faculty of Medicine Center for Therapeutic Apheresis and written informed consent was signed according to our institution regulations. Mostly bortezomib based regimens were given as induction therapy to our patients. Ninety two percent of the patients received only GCSF at a dose of 5 µg/kg BW twice-daily s.c. until stem cell procurement. Patients underwent further PBSC collections until we obtained the target dose >20 CD34+ cells/µL blood. A maximum of 3 collections were performed in the first mobilization; if the cell dose was not achieved, we submitted patients to a second mobilization.Results: Forty-one of 301 patients were above 65 years of age (median age 68, range 65-75) and 260 patients were below the age of 65 (median age 56, range 29-64). Baseline characteristics of the older and younger patient cohorts are summarized in Table-1. The median follow-up was 48.5 months (range 1-90) for age <65 years old patients and 46 months (range 1-90) for age ≥65 years old patients. Mobilization regimens for the younger patient population were G-CSF only (n:241), cyclophosphamide based (n:12) and +plerixafor (n:7). Mobilization in the older population was with cyclophosphamide based (n:4), G-CSF only (n:36) and +plerixafor (n=1) in whom poor mobilization had been predicted. The chemotherapy regimens were not statistically different between both age groups (chi square p value 0.37). There were no significant statistical differences in time from diagnosis to mobilization, number of prior therapies or disease status between both patient groups. The number of CD34-positive circulating cells before scheduled leukapheresis was mean 23.26 cells/μL in all patients (including patients who failed mobilization). Neutrophil engraftment was seen faster in elderly group (mean 10.4±3.1 vs. 11.5±1.8; p=0.008) but platelet engraftment was similar compared the younger patients with older ones (Table-2). In The probability of 5-year progression free survival (PFS) and overall survival (OS) in elderly patients with ISS-3 was 82.4%±12.1% and 48.5±16.5%. No statistical significance was observed for mean estimated 5-year OS in terms of patient age (<65 and ≥65 years; 82.5%±2.8% and 74.3%±8.7% p=0.29) (Figure-1). Less relapse was occurred in elderly cohort (17.5% vs. 35.4%) but the number of patients in this group does not provide enough statistical power to confirm whether the differences in PFS were statistically significant.Conclusion: To date, accepted approach for elderly patients with MM is not only improving survival, also their quality of life. Based on this single center study, auto-HSCT is safe and efficient in the treatment of elderly myeloma patients but no statistical difference was demonstrated in respect to age groups. [Display omitted] DisclosuresIlhan:Novartis: Consultancy.

Pilot Study of Safety and Efficacy of Chidamide in Allogenic Peripheral Hematopoietic Stem Cell Transplantation: Better Disease Control and Positively Lower Graft Versus Host Disease

IntroductionThe combination of busulfan (Bu) and fludarabine (Flu) is an effective and well-tolerated hematopoietic stem cell transplantation (HCT) conditioning regimen for patients with acute leukemia. However, relapse remains the main reason for treatment failure. Increasing intensity of conditioning therapy leads to not only better control of disease, but more treatment related mortality including graft versus host disease (GVHD). Song and Partow demonstrated that introducing histone deacetylase inhibitor (HDACi) vorinostat into busulfan/fludarabine/clofarabine (Bu/Flu/Clo) could augment disease control in vitro and in vivo, without increasing toxicity. Pavan and Choi showed vorinostat decrease GHVD while preserving graft versus leukmia effect. We conducted a clinical trial to evaluate the role of a selective HDACi chidamide in allogenic HCT.MethodsChidamide was given orally twice weekly at dose of 20 mg from day -7 to 2 weeks post transplantation. Busulfan was administered intravenously at fixed dose of 3.2 mg/kg for 4 days from day -6 to -3. Fludarabine and cytarabine were given intravenously at dose of 30 mg/m2 and 1g//m2 respectively for 5 days from day -6 to -2. GVHD prophylaxis was based on post-transplantation cyclophosphamide (50 mg/kg on day +3, +4) and cyclosporine started from day +5. The presence of minimal residual disease (MRD) was determined by multi-parameter flow cytometry.ResultsForty patients (24 AML, 6 MDS, 10 ALL) with median age 41 years (range 16-60) received an allogeneic matched sibling (n=34) or unrelated donor (n=6) HCT in CR1 (n=15), CR2 (n=6), with residual disease (n=10), or with active disease (n=9). Seventeen patients had adverse risk karyotype according to European LeukemiaNet risk stratification. Median time to ANC > 0.5 x 109/L and platelets > 20 x 109/L were 16 (range 9-36) and 18 days (11-44), respectively. Short-term (before recovery of ANC and platelets) adverse events included neutropenic fever (80%), reversible grade 2 elevation of liver enzyme (42.5%), and grade 2 mucositis (27.5%). Median follow-up time of the whole cohort was 11.5 months (3-24.7). All patients achieved CR and clearance of MRD by day +30 after HCT. All patients achieved 100% donor chimerism at 30 days following HCT. The incidence of grades II-IV and grade III-IV acute GVHD is 11% and 5% respectively. Only one patient died of aGVHD. Chronic extensive GVHD among 38 evaluable patients is 9%. Median follow-up time of the whole cohort is 11.5 month (3-24.7). Estimated progression free survival and overall survival at 1 year are 75% and 84.6% respectively (Figure1-A). Patients with MRD have inferior survival compere with patients without MRD (81.2% vs 68% p=0.336) (Figure 1-B).ConclusionShort-term results indicate introducing chidamide into allogeneic HCT could lead to better control of disease and possible lower GVHD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Infused Autograft Absolute Lymphocyte Count Predicts Superior Survival in Diffuse Large B Cell Lymphoma Patients Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation: A Matched Case-Control Study

Our group published a double phase III trial showing that patients infused with an autograft absolute lymphocyte count (A-ALC) ≥0.5×109 cells/kg experienced superior survival post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). Based on the results from our phase III study, as well as published retrospective studies, on April 1, 2017, our Bone Marrow Transplant Program changed our standard practice to collect an A-ALC ≥0.5×109 cells/kg in addition to stem cells for lymphoma patients undergoing APBHSCT. The primary objective of the present study was to continue to assess the prognostic ability of A-ALC by evaluating overall survival (OS) and progression-free survival (PFS) of diffuse large B cell lymphoma (DLBCL) patients who underwent APBHSCT after April 1, 2017, compared with matched control groups at a 1:1:1 ratio with DLBCL patients infused with an A-ALC <0.5×109 cells/kg and A-ALC ≥0.5×109 cells/kg before April 1, 2017. Using the GREEDY algorithm, 85 DLBCL patients (cases) infused with an A-ALC ≥0.5×109 cells/kg after April 1, 2017, were matched at a 1:1:1 ratio with control groups of DLBCL patients who underwent transplantation before April 1, 2017: patients infused with an A-ALC <0.5×109 cells/kg (control 1) and patients infused with an A-ALC ≥0.5×109 cells/kg (control 2) before April 1, 2017. Groups were matched in terms of sex, age, stage, lactate dehydrogenase (LDH) level, performance status, extranodal disease, International Prognostic Index (IPI), and disease status before APBHSCT (complete or partial response). Survival follow-up was truncated at 3 years from the date of transplantation. Cases, control 1, and control 2 were balanced as to age (P=.8), sex (P=.9), LDH (P=.6), performance status (P=.5), extranodal disease (P=.2), IPI (P=.6), and disease status before APBHSCT (P=.2). Cases and control 2 showed superior OS and PFS compared with control 1. Multivariate analysis including all patients continued to show A-ALC ≥0.5×109 cells/kg as an independent predictor for OS (hazard ratio [HR], 0.382; 95% confidence interval [CI], 0.241 to 0.605; P < .0001) and PFS (HR, 0.437; 95% CI, 0.279 to 0.629; P < .0001). Our matched case-control study supports the results of previously published retrospective studies and our phase III study showing that the infusion of A-ALC is a prognostic factor for survival in DLBCL patients undergoing APBHSCT. Our findings support the practice of collecting not only enough stem cells for hematologic engraftment, but also enough immune effector cells (ie, A-ALC) to improve clinical outcomes in DLBCL patients post-APBHSCT.

Long-term results of allogeneic peripheral blood hematopoietic stem cell transplantation for severe aplastic anemia

ObjectiveAplastic anemia (AA) is a life-threatening disorder and may be associated with significant morbidity and mortality Currently, the first treatment option is allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients younger than 40 years. Bone marrow is recommended as the stem cell source due to less graft versus host disease (GVHD) risk and better outcomes than peripheral blood (PB)-derived stem cell. The aim of this study is to share the data of AA patients who have underwent PB-derived allo-HSCT in our bone marrow transplantation center. MethodsTwenty-seven patients who underwent PB-derived allo-HSCT from human leukocyte antigen matched sibling donors were analyzed retrospectively. ResultsThe median follow-up time was 95.2 months (range, 4.8–235 months). The 10-year survival was 89 %. The median neutrophil and platelet engraftment time was 11 days (range, 9–16 days) and 13 days (range, 11–29 days), respectively. Primary platelet engraftment failure was observed in 1 patient (3.7 %). Acute and chronic GVHD observed in 2 (7.4 %) and 3 (11.1 %) patients, respectively. Neutropenic fever was observed in 13 (44.8 %) of patients until the engraftment after allo-HSCT. One patient died due to CMV infections, two died due to septic shock secondary to fungal infection. ConclusionAlthough there is no prospective data directly comparing BM with PB as stem cell source in AA, observational studies indicates better OS with BM. PB can be used in certain situations such as higher risk for graft failure and donor preference. This study demonstrated that PB-derived stem cell seems to be a reasonable alternative to BM.

Evans syndrome after Allogenic Peripheral Hematopoietic Stem Cell transplantation in a child with Severe Acquired Aplastic Anemia: case report and literature review

Evans syndrome after Allogenic Peripheral Hematopoietic Stem Cell transplantation in a child with Severe Acquired Aplastic Anemia: case report and literature review

Infused Autograft-Absolute Lymphocyte Count Predicts Superior Survival in Diffuse Large B-Cell Lymphoma Patients Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation: A Matched-Control Study

Introduction Day 15 absolute lymphocyte count (ALC-15) recovery after autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) is recognized as a prognostic factor for survival. ALC-15 recovery is directly dependent on the amount of collected and infused autograft-absolute lymphocyte count (A-ALC). Our group published a double-blind phase III study which showed that patients infused with an A-ALC ≥ 0.5 x 109 cells/kg experienced superior survival post-APBHSCT. Based on the results from our phase III study, on April 1, 2017, our Bone Marrow Transplant Program changed our standard clinical practice to collect an A-ALC ≥ 0.5 x 109 cells/kg in addition to stem cells for lymphoma patients undergoing APBHSCT. To continue to assess the prognostic ability of A-ALC, we evaluated the overall survival (OS) and progression-free survival (PFS) of diffuse large B-cell lymphoma (DLBCL) patients that underwent APBHSCT after April 1, 2017 compared with a matched-control group in a 1:1:1 ratio with DLBCL patients infused with an A-ALC &amp;lt; 0.5 x 109 cells/kg or an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1, 2017. Methods Eight-five consecutive DLBCL patients after our practice changed on April 1, 2017 received an A-ALC ≥ 0.5 x 109 cells/kg. For each DLBCL patient infused with an A-ALC ≥ 0.5 x 109 cells/kg after April 1, 2017, the set of potential controls was restricted to those DLBCL patients infused with an A-ALC &amp;lt; 0.5 x 109 cells/kg and an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1 2017 . Within this group of potential controls, the subjects were chosen who best matched for the cases in terms of clinical risk variables, including gender, age, stage, lactate dehydrogenase (LDH), performance status, extra-nodal disease, International prognostic index (IPI), and disease status prior to APBHSCT (complete or partial response), using the GREEDY algorithm. Cases were defined as DLBCL patients infused with an A-ALC ≥ 0.5 x 109 cells/kg starting from April 1 2017. Control 1 was defined as DLBCL patients infused with an A-ALC &amp;lt; 0.5 x 109 cells/kg prior to April 1 2017. Control 2 was defined as DLBCL patients infused with an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1 2017. We truncated the survival follow-up to 3 years starting from the date of transplant to match follow-up time between cases and controls. Both matched cases and control groups patients received BEAM conditioning. This retrospective study was approved by the Mayo Clinic Institutional Review Board according to the regulation of the Declaration of Helsinki. Results Cases, control 1 and control 2 were balanced to the clinical risk variables; age (p = 0.8); gender (p = 0.9); LDH (p = 0.6); stage (p = 0.3); performance status (p = 0.5); extra-nodal disease (p = 0.2); IPI (p = 0.6); and clinical status prior to transplant (p = 0.2). Figure 1A showed the OS and figure 1B the PFS. Both the cases and control 2 showed superior OS and PFS in comparison to control 1. Cases and control 2 showed overall similar OS and PFS. Multivariate analysis including all patients continue to depict the A-ALC ≥ 0.5 x 109 cells/kg as an independent predictor for OS (HR = 0.382, 95%CI=0.241-0.605, p &amp;lt; 0.0001) and PFS (HR = 0.437, 95%CI = 0.279-0.629, p &amp;lt;0.0001). Subgroup analysis, including all patients, shows superior OS and PFS for patients infused with an A-ALC ≥ 0.5 x 109 cells/kg for each of the following clinical variables: age [&amp;gt; 60 years: OS (p &amp;lt;0.0001); PFS (p &amp;lt;0.0001) or ≤ 60 years: OS (p &amp;lt;0.01); PFS (p , 0.02)]; extra-nodal disease [&amp;gt; 1: OS (p &amp;lt;0.008); PFS (p &amp;lt;0.01) or ≤1: OS (p &amp;lt; 0.001): PFS (p &amp;lt;0.0005)]; IPI [&amp;gt; 2: OS (p &amp;lt;0.01); PFS (p &amp;lt;0.02) or ≤ 2: OS (p &amp;lt;0.0008); PFS (p &amp;lt;0.0006)]; LDH [abnormal: OS (p &amp;lt;0.006); PFS (p &amp;lt;0.005) or normal: OS (p &amp;lt;0.002); PFS (p &amp;lt;0.002)]; performance status [&amp;gt; 1: OS (p &amp;lt;0.04); PFS (p &amp;lt;0.03) or ≤ 1: OS (p &amp;lt;0.0001); PFS (p &amp;lt;0.0001)]; stage [I/II: OS (p &amp;lt;0.006); PFS (p &amp;lt;0.006) or III/IV: OS (p &amp;lt;0.002); PFS (p &amp;lt;0.001)]; response prior to transplant [complete response: OS (p &amp;lt;0.0007); PFS (p &amp;lt;0.0001) or partial response: OS (p &amp;lt;0.01); PFS (p &amp;lt;0.02)]. Conclusion Our match-control study continues to support the results of our Phase III study showing that the infusion of A-ALC is a prognostic factor for survival of DLBCL patients undergoing APBHSCT. Our studies support the practice of not only collecting enough stem cells (i.e., CD34) for hematologic engraftment, but also enough immune effector cells (i.e., A-ALC) to improve clinical outcomes in DLBCL patients post-APBHSCT. Figure 1 Disclosures Ansell: Regeneron: Research Funding; Bristol Myers Squibb: Research Funding; Trillium: Research Funding; ADC Therapeutics: Research Funding; Takeda: Research Funding; AI Therapeutics: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding.

Long-Term Results of the Treatment of Persons with Hodgkin's Lymphoma in a Resource-Constrained Setting: Real-World Data from a Single Center

Background: Hodgkin's lymphoma (HL) is the model of curative care with radiation therapy, combination chemotherapy, staging approaches, peripheral blood stem cell transplantation, and immunotherapy. However, the value of the novel anti cancer drugs has been recently analyzed and questioned in view of the results in the real improvement of overall survival (OS). Material and methods: All consecutive patients seeking medical care after 1986 in our institution as a result of HL and followed for at least 3 months were entered in the study. A diagnosis of HL was based on the histological study of a pathology specimen, mainly a lymph node; the same pathologist analyzed all the specimens and defined the histological subtype. Clinical stage was defined according to the Ann Arbor classification. Bone marrow biopsies were done only in patients with clinical stages III or IV. Computed tomography (CT) scans were done in all cases, prior to starting the treatment. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans were performed since 2002. Between 1986 and 1997, patients were treated with MOPP, and after 1997 with ABVD as frontline therapy. For stages I and II, four cycles of chemotherapy were delivered and a computerized tomography (CT) scan was performed; if lymph node enlargement were present at this point in time, four additional cycles were given, whereas two additional cycles were given if the CT scan was negative. For stages III and IV, the CT scans were performed at the end of six cycles and two or four more cycles. Mediastinal radiotherapy was delivered only to persons with a positive FDG-PET scan at the end of the treatment. Patients showing activity after these treatments were considered as refractory and treated with four courses of ICE (ifosfamide, carboplatin and etoposide). Autologous or allogeneic peripheral blood hematopoietic stem cell transplants (HSCT) were given to refractory patients after achieving a complete remission (CR): High-dose melphalan (200mg/m2) was employed in autologous transplants, whereas cyclophosphamide, fludarabine and busulfan were employed in allogeneic transplants, all of them from HLA-identical siblings. After the completion of the treatment, patients were every two months for one year and every four months later on. No FDG-PET scans were done during the follow up, unless clinically indicated. Results: Among 91 patients with HL identified between 1986 and 2020, 88 were followed three months or more and were included in the analysis. There were 37 females and 51 males. The median age was 29years (range5-73years). There were 62 patients with nodular sclerosing HL (70%), 19 mixed cellularity (HL), 2 lymphocyte depleted HL, and one lymphocyte predominant HL; in 4 cases the histologic variant could not be defined. According to Ann Arbor classification, 5 patients were found in stage I, 48 in stage II, 19 in stage III and 16 in stage IV. Ten patients presented with a mediastinal mass larger than 10 cm. in the chest X-ray film. Three cases presented with relapsed disease. Patients have been followed for a median of 114 months (range4-402). 44 patients are alive, 10 have died and 34 were lost to follow-up. Median OS for all the patients has not been reached, being above 402 months, the OS at 310 months is 88% and at 402 months 77%. Median OS has not been reached and is above 94, 109, 90 and 98 months for stages I, II, III and IV, respectively (p=0.2). The 310-month OS was 83% for patients treated with MOPP and 88% for those treated with ABVD (HR:0.76, 95% CI 0.2-2.8; p=0.6).Sixteen patients (18%) were refractory to the treatment and 9 (10%) relapsed; they were treated with ICE followed by HSCT (autologous 15 patients and allogeneic 10 patients). Patients who underwent auto-HSCT had a median survival of 329.1 months and an OS of 92.3%, whereas those given allo-HSCT had a median survival of 59.3 months and an OS of 45.7% (HR0.2, 95%CI 0.04-1.3, p=0.057). The OS of patients given or not HSCT was 73.5% and 92.9% at 266 and 404 months, respectively (HR4.09, 95%CI 1.0-16.6, p=0.01). The OS was similar. The causes of death were breast carcinoma in 2 cases, liver carcinoma in one and uncontrolled lymphoma activity in the remaining. Conclusion: HL may be less aggressive in Mexican population than in Caucasians. Combined chemotherapy renders acceptable results, irrespective of clinical stage. Disclosures No relevant conflicts of interest to declare.

Clinical Significance of Serum Immunoglobulin Level after Peri- pheral Blood Haploidentical Hematopoietic Stem Cell Transplantation in Patients with Hematologic Malignancies

To investigate the clinical significance of post-transplantation serum immunoglobulin level in the outcome of patients with hemalologic malignancies treated by haploidentical peripheral hematopoietic stem cell transplanta-tion(Haplo-HSCT). The clinical data of 157 patients treated by haplo-HSCT were analyzed retrospectively. The overall survival rate (OS), graft versus host disease (GVHD) incidence, infection incidence, serum immunoglobulin level, the relationship of immunoglobulin levels with OS and transplant complications were analyzed. The 2-year OS rate was 59.2%(95%CI:51.6%-66.9%), 2-year relapse mortality was 11.5%(95%CI: 6.4%-16.6%), and non-relapse mortality was 29.3%(95%CI:21.7%-36.9%). The cumulative incidence of III-IV aGVHD was 16.6%(95%CI:10.8%-22.9%); the cumulative incidence of extensive cGVHD was 21.7%(95%CI:15.3%-28.6%); the cumulative incidence of severe bacterial infection within 1 year was 59.2%(95%CI:51.6%-66.2%); the cumulative incidence of invasive fungal infection was 47.1%(95%CI:38.9%-54.8%). The occurrence of extensive cGVHD after haplo-HSCT related with the gender match of donor-recipient and bacterial infection. The levels of IgG in patients with 0-II aGVHD and patients with III-IV aGVHD for 1 month after haplo-HSCT were (6.96±2.47) and (4.27±2.42) g/L （P=0.003）, IgG levels at 3 months afte haplo-HSCT were (8.71±4.47) and (6.65±2.95) g/L (P=0.038); IgG levels at 1 month after haplo-HSCT showed predictive value for III-IV aGVHD susceptibility(P=0.003); for patients with IgG<4 g/L at any time after haplo-HSCT, the incidence of extensive cGVHD was significantly increased (35.5% vs 18.3%) (P=0.037), the incidence of fungal infection within 1 year after haplo-HSCT was significantly increased(71.0% vs 41.3%) (P=0.003), and the 2-year survival rate was reduced significantly (P=0.035). Haplo-HSCT is effective for the treatment of hematologic malignancies. Patients with lower IgG at 1 month after haplo-HSCT are more likely to develop III-IV aGVHD, and IgG levels at 1 month after haplo-HSCT can predict its susceptibility to a certain extent. Patients with severe hypoimmunoglobulinemia (IgG<4 g/L) after haplo-HSCT are more likely to develop extensive cGVHD, fungal infection and show worse survival prognosis.

Long-term results of allogeneic peripheral blood hematopoietic stem cell transplantation for severe aplastic anemia

Abstract Objective Aplastic anemia (AA) is a life-threatening disorder and may be associated with significant morbidity and mortality Currently, the first treatment option is allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients younger than 40 years. Bone marrow is recommended as the stem cell source due to less graft versus host disease (GVHD) risk and better outcomes than peripheral blood (PB)-derived stem cell. The aim of this study is to share the data of AA patients who have underwent PB-derived allo-HSCT in our bone marrow transplantation center. Methods Twenty-seven patients who underwent PB-derived allo-HSCT from human leukocyte antigen matched sibling donors were analyzed retrospectively. Results The median follow-up time was 95.2 months (range, 4.8–235 months). The 10-year survival was 89 %. The median neutrophil and platelet engraftment time was 11 days (range, 9–16 days) and 13 days (range, 11–29 days), respectively. Primary platelet engraftment failure was observed in 1 patient (3.7 %). Acute and chronic GVHD observed in 2 (7.4 %) and 3 (11.1 %) patients, respectively. Neutropenic fever was observed in 13 (44.8 %) of patients until the engraftment after allo-HSCT. One patient died due to CMV infections, two died due to septic shock secondary to fungal infection. Conclusion Although there is no prospective data directly comparing BM with PB as stem cell source in AA, observational studies indicates better OS with BM. PB can be used in certain situations such as higher risk for graft failure and donor preference. This study demonstrated that PB-derived stem cell seems to be a reasonable alternative to BM.

Efficacy of autologous versus allogeneic peripheral blood hematopoietic stem cell transplantation in non-high-risk acute myeloid leukemia patients in first complete remission

Efficacy of autologous versus allogeneic peripheral blood hematopoietic stem cell transplantation in non-high-risk acute myeloid leukemia patients in first complete remission

Influencing Factors and Prevation of Infection in Leukemia Patients after Allogeneic Peripheral Blood Stem Cell Transplantation

To explore the influencing factors and countermeasures of infection in leukemia patients after allogeneic peripheral blood hematopoietic stem cell transplantation. A total of 126 patients with leukemia admitted in our hospital from August 2016 to March 2018 were selected. The number of infected patients after transplantation was recorded, and the causes of infection were analyzed. Among the 126 patients, 43 were positive for infection, and the infection rate was 34.13%. A total of 89 pathogens were detected, of which bacteria accounted for 64.05%; virus accounted for 22.47%, and fungi accounted for 13.48%. The patient's age, donor type, pre-transplant infection, prophylactic use of antibiotics and aGVHD all were factors influencing the patient's infection (P＜0.05). The follow-up results showed that the incidence of infection in the intervention group significantly decreased after intervention with prevention program (P＜0.05). After reasonable nursing intervention, the incidence of infection in the intervention group after follow-up for 12 months was lower than that in the control group (P＜0.05). Pre-transplant infection and prophylactic use of antibiotics are factors influencing the infection after allogeneic hematopoietic stem cell transplantation. The incidence of infection can be reduced by reasonable infection prevention.

Outcome of peripheral blood allogeneic hematopoietic stem cell transplantation as a treatment option in patients with severe aplastic anemia between 40 and 50 years

The frontline treatment for patients younger than 40 years with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-identical sibling donor. However, in patients with severe AA who are older than 40 years, allogeneic HSCT has been found to be associated with increased treatment-related mortality and toxicity, even when matched sibling donors are used. We report our institutional experience with allogeneic HSCT in patients with severe AA between 40 and 50 years. A total of 19 patients with severe AA were included in the study. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan–Meier method. The mean age of patients at the time of transplant was 43.79 years, and 57.9% were male. The mortality rate was 36.8%, attributed to infection (10.5%), relapse (15.8%), and renal failure (5.3%) in all cases. Acute graft-versus-host disease (GVHD) occurred in five patients (26.3%), and chronic GVHD occurred in two patients (10.5%). The 5-year OS was 62% and the 5-year DFS was 52%. We found that the patient's age, platelet level prior to transplantation, and the number of CD3 cells infused for each transplant were independent prognostic factors for OS, and the age and sex of the patient, graft rejection, and platelet level prior to transplantation were significant prognostic factors associated with DFS. We recommend that immunosuppressive therapy be considered as a first-line treatment in patients with severe AA who are older than 40 years. Allogeneic HSCT can be considered a valid alternative option in patients whose suppression therapy fails.

Outcome of donor lymphocyte infusion for fall in chimerism after hematopoietic stem cell transplant

Achievement of complete donor chimerism after an allogeneic hematopoietic stem cell transplant is necessary for elimination of underlying malignant disease. A decline in donor chimerism may herald an impending relapse and therefore, early recognition and intervention plays an important role in such cases. A 32 year old male patient diagnosed as a case of Philadelphia positive mixed phenotypic acute leukaemia underwent peripheral blood hematopoietic stem cell transplant (HSCT) with his sibling as donor. During follow-up, a fall in donor chimerism was observed from 91.86% on day +37 to 88.83% on day +57 and 85.34% on day +77. Donor Lymphocyte Infusion (DLI) was harvested via apheresis. A dose of 1 × 106 per kg was infused and the rest was cryopreserved in aliquots of escalating doses. On day +102, he presented with biopsy proven acute mucocutaneous GVHD grade 2 which was managed conservatively and donor chimerism of 57.99%. On day +126, a repeat donor chimerism was performed which showed 100% chimerism. He continues to do well at day +161. Timely use of DLI can improve donor chimerism in patients with Philadelphia positive acute leukaemia who tend to relapse after HSCT.

Clinical and Pathological Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

To explore the clinical manifestation, pathological features and treatment regimen of blastic plasmacytoid dendritic cell neoplasm (BPDCN). The clinical and pathologic features, diagnosis, treatment and prognosis of 5 BPDCN patients were analyzed retrospectively. 5 patients had skin lesions, and bone marrow involvement. The immunohistochemical staining showed that the CD56 expression was observed in 5 patients, CD4 and CD123 in 4 patients, and CD43 expressed in 3 patients. After initial treatment, 3 patients achieved complete remission and 1 patient did not. One patient showed disease progression after partial remission for 1 month. Two young patients underwent sibling allo-PBHSCT, and then achieved long-term survival. BPDCN often presents skin lesions as the first symptom, moreover, soft tissues, lymph nodes and bone marrow were involved, which suggested the disease progresses. There is currently no uniform treatment protocol for this disease. Active allogeneic peripheral blood hematopoietic stem cell transplantation in the CR1 phase for appropriate patients may increase their chances for long-term survival.

Clinical Analysis of Dasatinib and Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

To investigate the clinical efficacy, related side-effectt and long-term survival condition of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) patients treated with second generation TKI dasatinib and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Clinical data of 19 newly diagnosed as Ph+ ALL patients treated by dasatinib, chemotherapy and allo-HSCT from January 2012 to September 2018 were collectd and analyzed. There were 10 males and 9 females with median age of 29 years old. 14 patients were BCR/ABL P190 positive while 5 with BCR/ABL P210 positive. Three patients had complex karyotype, and 3 cases were confirmed to have central nervous system leukemia. All the patients received treatment with the induction chemotherapy regimen of VDCLP and consolidation regimens such as HD-MTX and MAE. 11 patients (57.9%) received dasatinib during induction chemotherapy, 3 patients (15.8%) received dasatinib after remission and 5 patients (26.3%) received dasatinib to replace imatinib. Side-effect appeared in 3 patients including rash, edema and nausea. All the patients got morphological remission and 7 patients(63.6%) got MMR after 4 weeks of induction chemotheraphy. 17 patients (89.5%) got MMR and 15 patients(78.9%) got CMR before allo-HSCT. All the patients received related bone marrow and peripheral hematopoietic stem cell transplantation from related donors, the median time of WBC and platelet engraftment were 12 d and 14 d after transplantation, respectively. The incidence rate of aGVHD and cGVHD were 42.1% and 57.9% respectivety. 13 patients received therapy of dasatinib after HSCT but 7 patients discontinued because of severe headache, vomiting and serious effusions. All the patients were followed-up for the median time of 42 months, the 3-year and 5-year OS both were 94.4%, and 3-year and 5-year RFS of 81.9% and 71.6%, respectively. First-line administration of dasatinib and chemotherapy followed by allo-HSCT for treatment of Ph+ALL is effective and patients can well-tolerate, the patients long-tern survival maybe superior to that of the patients treated with first generation TKI.

Protective Effects of Cytomegalovirus DNA Copies ≧1000/mL for AML Patients in Complete Remission After Single Cord Blood Transplantation.

IntroductionCurrent consensus recommends a protective effect of cytomegalovirus (CMV) infection on relapse after peripheral blood or bone marrow hematopoietic stem cell transplantation. However, in cord blood transplantation (CBT), studies of CMV infection, especially CMV viral load, on relapse are limited.Patients and MethodsWct e retrospectively analyzed the effect of CMV infection on 3-year outcomes in 249 AML patients according to CMV DNA load (DNA copies <1000/mL and DNA copies ≧1000/mL) within 100 days after CBT. Furthermore, eight-colour flow cytometry was used to detect peripheral blood lymphocyte subsets in 38 patients who received CBT in the last year, and 10 healthy volunteers were included as controls.ResultsThe results showed that CMV DNA load did not affect the cumulative incidence of relapse in the whole study population. However, in patients with complete remission status before transplantation, the high CMV DNA load group showed a significantly reduction of relapse than the low CMV DNA load group (3.9% vs 14.6%, p=0.012, respectively), which was confirmed by multivariate analysis (HR 0.23; 95% CI, 0.07–0.73, p = 0.012). Surprisingly, high or low CMV DNA load did not significantly affect non-relapse mortality or overall survival (18.0% vs 17.0%, p=0.777 and 79.0% vs 74.6%, p=0.781, respectively). Besides, the absolute number of CD8+ T cells were increased in the high CMV DNA load group compared with the low DNA load group 1 month after CBT (0.20×109/L vs 0.10×109/L, p=0.021, respectively).ConclusionDNA copies ≧1000/mL for AML patients in complete remission was associated with a lower incidence of relapse after CBT, which might partly result from the expansion of CMV-related CD8+ T cells.

Rabbit ATG/ATLG in preventing graft-versus-host disease after allogeneic stem cell transplantation: consensus-based recommendations by an international expert panel

This collaborative initiative aimed to provide recommendations on the use of polyclonal antithymocyte globulin (ATG) or anti-T lymphocyte globulin (ATLG) for the prevention of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). A comprehensive review of articles released up to October, 2018 was performed as a source of scientific evidence. Fourteen clinically relevant key questions to the domains indication, administration, and post-transplant management were developed and recommendations were produced using the Delphi technique involving a Panel of 14 experts. ATG/ATLG was strongly recommended as part of myeloablative conditioning regimen prior to matched or mismatched unrelated bone marrow or peripheral blood allogeneic HSCT in malignant diseases to prevent severe acute and chronic GvHD. ATG/ATLG was also recommended prior to HLA-identical sibling peripheral HSCT with good but lesser bulk of evidence. In reduced intensity or nonmyeloablative conditioning regimens, ATG/ATLG was deemed appropriate to reduce the incidence of acute and chronic GvHD, but a higher risk of relapse should be taken into account. Recommendations regarding dose, application, and premedication were also provided as well as post-transplant infectious prophylaxis and vaccination. Overall, these recommendations can be used for a proper and safe application of polyclonal ATG/ATLG to prevent GvHD after allogeneic HSCT.

Improvement of Survival in JMML By Induction Regimen of Decitabine + Cytarabine + Fludarabine before Hematopoietic Stem Cell Transplantation: Study of 33 Cases in Single Center

OBJECTIVE: Pre-transplant chemotherapy can control progression of primary disease, alleviate disease and improve disease-free survival after transplantation in juvenile granulocyte leukemia (JMML).Methylation abnormalities play an important role in the development of JMML. This study was to explore the effectiveness of induction regimen including decitabine ,cytarabine and fludarabine before transplantation and to explore the affection to transplantation in JMML. METHODS: A retrospective analysis of the remission and survival of 33 children with JMML before and after stem cell transplantation in the Department of Pediatrics of Nanfang Hospital from 2014.2 to 2019.7. There were fourteen girls and 19 boys, median diagnosis age 23 months(2m-10 years old). Median white blood cell count,median hemoglobin level,median platelet count( WBC) was 29.3G/L (6.29-158.66G/L); 83g /L(41-113g/L,); 27.17G / L(4-431G / L) respectively. Median Hemoglobin F level was 34.16%( 1.56-78%). Median spleen level under the costal margin was 5cm(0-13.3cm); Median liver under the costal margin was 3.9 cm(0 -8.9 cm) .There were 26 cases with the pulmonary involvement (26/33, 78.8%). The original blast cells in bone marrow were 0-8.8%, with a median of 4.5%.Mutant genes including: 2 cases of KAS, 9 cases of NF1, 2 cases of NRAS, 16 cases of PTPN11, and 4 cases without common JMML gene .The first course of treatment after diagnosis is 20 mg/m2 × 5 days of decitabine. The second course of treatment is DA: decitabine 20 mg/m2 × 5 days + cytarabine 100 mg/m2 × 5 days or A-3V regimen: Ara-C 100 mg/m2/d CIV×7 days+Etoposide 100 mg/m2/d ×5 days+Vincristine 1.5 mg/m2/d ×1 day. The third course of treatment is decitabine 20 mg/m2 × 5 days,then FLAG regimen: Fludarabine 30mg / m2 × 5 days, Ara-C 1 g / m2 × 5 days, G-CSF 5μg / Kg × 6 days. Single drug of decitabine 20 mg/m2 × 5 days was adminstered 1-3 times per monthly during the period of waiting for transplantation. Comprehensive assessment was performed before transplantation. Survival outcomes were analyzed by Kaplan-Meier curves. RESULTS: At least 3 courses of chemotherapy were completed in 33 cases, including 1-5 courses of decitabine.The bone marrow was evaluated in 31 patients before transplantation: 12 patients got complete remission(CR) and 19 patients got partial remission(PR) .Peripheral blood evaluation: 23 cases achieved WBC CR; 17 cases achieved platelet CR, 6 cases achieved platelet PR, 7 cases had no improvement. Eighteen cases of spleen were evaluated, of which only 3 cases were CR, 13 cases were PR, and 2 cases did not improve. Overall assessment, only 1 case achieved CR before transplantation, 1 case did not improve, and 31 cases achieved PR .Allogeneic hematopoietic stem cell transplantation was performed in 33 cases, including 3 cases of nonrelated peripheral blood hematopoietic stem cell transplantation(PB HSCT), 30 cases of complementary transplantation (haploid identical PB HSCT plus non-related cord blood transplantation). The median follow-up time after transplantation was 22m(3-63m).There was no death in the period of chemotherapy before transplantation. Four patients relapsed after transplantation, and One patient died of transplantation related death. Three years EFS was 80.6%. Conclusion: Pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine is safe, effective and feasible. The response rate of treatment is 97.0%, although the complete remission rate before transplantation is low, most of them are partial remission, but the disease-free survival after non-related HSCT or complementary transplantation could reached to 80.6%. These results indicated that pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine was benefit to improved the survival of children with JMML after HSCT. Figure 1 Disclosures No relevant conflicts of interest to declare.

Tocilizumab for Prophylaxis of Cytokine Release Syndrome after Outpatient-Based Haploidentical T-Cell Replete Peripheral Blood Stem Cell Transplantation

Introduction Cytokine release syndrome (CRS) is a common and potentially severe toxicity associated with haploidentical peripheral blood hematopoietic stem cell transplantation (Haplo-HSCT). CRS is characterized by immune activation and a high level of circulating inflammatory cytokines, particularly interleukin-6 (IL-6). While tocilizumab, an IL-6 receptor-targeted monoclonal antibody has been effectively used to treat CRS in the context of immunotherapy, it has not been evaluated during the acute Haplo-HSCT period. We hypothesized that prophylactic tocilizumab can prevent CRS after Haplo-HSCT. We report the results of a pilot trial to evaluate its use. Methods Patients ≥18 years undergoing Haplo-HSCT of peripheral blood in a single center with any underlying diagnosis were included. The conditioning was myeloablative and was administered as follows: cyclophosphamide 350 mg / m2 and fludarabine 25 mg / m2 (days -5-3) or rabbit antithymocyte globulin (2.5 mg / kg days -4, -3), plus melphalan 200 mg / m2 PO (days -2-1). Prophylaxis of graft versus host disease (GVHD) consisted of cyclophosphamide (50 mg / kg / day, days +3 and +4), cyclosporine and mycophenolate mofetil on day +5. The cells were infused on day 0. Tocilizumab was administered on day -1 in a single dose of 4 mg / kg IV. CRS was rated according to Lee et al. The primary outcome included the incidence and severity of CRS, the adverse effects associated with tocilizumab, hospitalization and graft rates and the incidence of GVHD. Results Ten patients have enrolled, with an average age of 26 years (range 19-32). The underlying diagnoses were acute lymphoblastic leukemia (n = 7), acute myeloid leukemia (n = 1) and non-Hodgkin lymphoma (n = 2). There were no infusion reactions associated with tocilizumab. Six patients (60%) developed CRS, all grades 1-2, with a median day of onset on day +2 (range 1-3) and a median fever duration of 2 days (range 2-3), often accompanied by nausea, diarrhea, dehydration and transaminitis. All patients were hospitalized; hospitalization was not related to CRS in three patients. 4 patients are alive without relapse (40%), 2 patients alive with relapse (20%), 3 patients died due to transplant-related mortality (30%), one patient dies from relapse (10%). No graft failure occurred and mixed chimerism was observed in a patient. Acute GVHD with steroid response has been diagnosed in 2 cases (20%, grade I / II). The median follow-up is 8.3 months (range 0-20). Conclusion What we observe about the prophylactic use of tocilizumab for Haplo-HSCT of peripheral blood is that its administration is feasible, Grades 1-2 CRS was observed in 60% of patients, grades 3-4 were not observed, however the use of tocilizumab did not prevent hospitalizations. More feasibility data is required before starting a definitive randomized trial to evaluate the use of tocilizumab for Haplo-HSCT peripheral blood. Disclosures Gomez-Almaguer: Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. OffLabel Disclosure: Tocilizumab for Prophylaxis of Cytokine Release Syndrome