Allogeneic HSCTs Research Articles

Monitoring and Management of Cytomegalovirus Reactivations After Allogeneic Hematopoietic Stem Cell Transplantation in Children: Experience from a Single Pediatric Center

Background: CMV reactivation represents a frequent complication after HSCT. The aim of this study was to describe the incidence of CMV reactivation in a pediatric HSCT cohort and analyze the potential impact of recipient/donor-related or transplant-related factors on this complication. Furthermore, we analyzed the management of CMV reactivation in order to purpose criteria for pre-emptive therapy. Methods: Allogeneic HSCTs, performed at IRCCS Istituto Gaslini between 2012 and 2022, were included in this analysis. CMV–DNAemia was regularly monitored. Risk stratification was based on donor/recipient serological status and additional potential risk factors were considered: haploidentical transplant; any HSCT subsequent to the first; acute and chronic GvHD; steroids; and other immunosuppressive therapies. We described also the approach for pre-emptive therapy during the period 2012–2019. Results: A total of 214 allogeneic HSCTs were performed in 189 patients. In total, 100 (46.7%) HSCTs were complicated by at least one reactivation. CMV reactivation was significantly associated with high serological risk and steroid treatment. Pre-emptive therapy was administered in 59/69 (85.5%) HSCTs during 2012–2019. In the presence of predefined risk conditions, therapy was started at a median viremia of 2050 copies/mL. No difference was observed in OS between patients with CMV reactivation versus patients who did not present this complication. Conclusions: These results suggest the potential effectiveness of the approach used in providing pre-emptive therapy based on viral load monitoring and individualized risk factors.

The prophylactic application of low-dose rabbit antithymocyte globulin in matched siblings HSCT with high-risk factors for graft-versus-host disease

Relapse and graft-versus-host disease (GVHD) are currently the predominant causes of mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The contentious use of antithymocyte globulin (ATG) for preventing GVHD in matched sibling HSCT scenarios has been a topic of significant debate. A retrospective analysis was conducted on matched sibling HSCT cases with high-risk factors for GVHD in our center from January 2018 to June 2023. Our assessment revealed that the group administered with ATG exhibited a 30 % incidence of acute GVHD (aGVHD), in contrast to 81.8 % in the non-ATG cohort (P = 0.037) among matched sibling HSCT cases with high GVHD risk factors. Furthermore, chronic GVHD (cGVHD) occurred in 20 % of the ATG group and 72.7 % of the non-ATG group (P = 0.03). Notably, the administration of ATG did not significantly impact disease relapse (p = 0.149), infection rates (p = 0.64), granulocyte recovery time (p = 0.15), platelet recovery time (p = 0.12), overall survival (p = 0.889), or disease-free survival time (p = 0.787). The use of rabbit antithymocyte globulin (r-ATG) at a 5 mg/kg dosage demonstrated a notable reduction in aGVHD and cGVHD incidences within sibling matched HSCT cases with high-risk factors for GVHD, without increasing rates of disease recurrence or infections. These findings highlight the potential benefit of using low-dose r-ATG in high-risk of GVHD sibling matched allogeneic HSCTs, although further validation with a larger cohort is necessary.

Current incidence, severity, and management of veno-occlusive disease/sinusoidal obstruction syndrome in adult allogeneic HSCT recipients: an EBMT Transplant Complications Working Party study

The current incidence, diagnostic policy, management, and outcome of VOD/SOS at EBMT centers were studied. All centers that had performed allogeneic HSCTs in adult patients within one defined year were invited to the study. Seventy-one centers participated with a total of 2886 allogeneic transplantations and 93 cases of VOD/SOS in 2018. The cumulative incidence of VOD/SOS at day 21 was 1.8% and at day 100 2.4%. Of 67 cases with detailed data, 52 were classical and 15 (22%) late onset (>day 21). According to the EBMT criteria, 65/67 patients had at least two VOD/SOS risk factors. The severity grades were: mild 0, moderate 3, severe 29, very severe 35. Fifty-four patients were treated with defibrotide. VOD/SOS resolved in 58% of the patients, 3/3 with moderate, 22/28 with severe, and 12/33 with very severe grade (p < 0.001). By day 100, 57% of the patients were alive; 3/3 with moderate, 22/29 with severe, and 13/35 with very severe VOD/SOS (p = 0.002). In conclusion, the incidence of VOD/SOS was low. Severe and very severe grades dominated. Very severe grade predicted poor outcome compared to severe grade further supporting the concept of early diagnosis and treatment to avoid a dismal outcome.

Improved Overall Survival of Patients Treated with Abatacept in Combination with a Calcineurin Inhibitor and Methotrexate Following 7/8 HLA-Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation: Analysis of the Center for International Blood and Marrow Transplant Research Database

Improved Overall Survival of Patients Treated with Abatacept in Combination with a Calcineurin Inhibitor and Methotrexate Following 7/8 HLA-Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation: Analysis of the Center for International Blood and Marrow Transplant Research Database

The Impact of Foundation of the National Turkish Donor Registry, Turkok on Donor Matching Kinetics

Purpose: Turkish Stem Cell Coordination Center (TURKOK) was established by the Turkish Ministry of Health in April 2015 in order to facilitate unrelated hematopoietic stem cell (HSC) transplantation in Turkey. The donor recruitment task has been linked to the Turkish Crescent's (National Blood Product Provider) nationwide distributed branches. As of July 2017, more than 300.000 volunteer donors are registered into the database. As of July 2017 they have facilitated more than 300 HSCTs. Transplant Registry Istanbul (TRIS) and Transplant Registry Ankara (TRAN) are two University affiliated donor search - co-ordination centers, which are officially responsible for the search, matching and organization of the delivery for unrelated donor HSC in Turkey. The foundation of TURKOK should have theoretically decreased our time spent to find a suitable matched donor. The aim of this study is to compare the time frames between admission, confirmation, work-up, and infusion of HSC between TURKOK and other WMDA or NMDP facilitated International Volunteer Donor Registries.Subjects & Methods: In 2015 1000 allogeneic HSCTs were peformed in Turkey and only 18% were from MUDs. This is a single center analysis of a dedicated active HSCT center, which is performing >70 allogeneic HSCTs per year and utilizing alternative donor sources >50%. Patient charts were reviewed retrospectively and 51 patients who admitted to our center within 2015-2017 for various high risk hematological malignancies (mostşy acute leukemia, in which allogeneic HSCT was indicated, were identified for this study. Patients were divided into two groups: (1) Patients who had received HSC from matched unrelated donors (MUD-T) (10/10-9/10) facilitated by TURKOK (N=36) ; (2) 15 patients who had received HSC from International Registries facilitated by TRIS or TRAN (MUD-I) . The duration between application and finding a suitable match (tAM), duration between matching and confirmation (tMC) and time from application to HSC transplantation (tATX) were calculated for each of these two groups. The time duration between admission and donor identification and admission to HSCT were not distributed normally. The mean values were compared between two groups by Mann-Whitney U test. p < 0.05 was considered statistically significant.Results: In 51 HSC recipients the overall median durations for tAM, tMC and tATX were 71 (range, 1-172), 33 (range, 1-181) and 97 (range, 13-172), respectively. In MUD-I overall median durations for tAM, tMC and tATX were 90 (range, 1-170), 40.5 (range, 1-181) and 98 (range, 13-172), whereas in MUD-T the timelines for tAM, tMC and tATX were 37 (range, 4-172), 17 (range, 6-151) and 96 (range, 73-128), respectively. The p values for comparative analysis betwen MUD-I and MUD-T for tAM, tMC and tATX were p=0.005, p=0.007 and p>0.05, respectively.Conclusion: In this relative limited size of HSC recipients from MUDs we observed accelerated kinetics for tAM and tMC, which means having a National Registry have a positive impact on finding an available match and confirmation process. On the other hand this improvement did not translate into rapid HSCT. The tATX between MUD-I and MUD-T are not significant. TURKOK has to establish and improve the organization of confirmed donor for collection of HSCs. The decreased timeline from application to confirmation is encouraging, but the time spent from confirmation to work/up and collection are still high. As TURKOK is a recently established donor bank, there is room for improvement. DisclosuresNo relevant conflicts of interest to declare.

The impact of chimerism on DNA-based human identification from skin surface cells of post-allogenic hematopoietic stem cell transplantation (HCST) patients

The use of biological traces recovered from touched or handled items increased with the advance of the forensic analysis system. Thus, DNA profiles obtained from touch DNA became a useful tool in forensic investigation. However, a chimeric person with more than one chromosomal population can be challenging for a forensic analyst. We investigated the genetic profile in blood, buccal swab, and skin swabs from twenty-four recipients aged 21–63 years who underwent a matched sibling allogeneic hematopoietic stem cell transplantation with no sign of skin graft versus host disease. Autosomal short tandem repeats genotyping was performed to evaluate chimerism status at 15 loci along with gender marker Amelogenin. According to our results, donor chimerism was detected in all recipient's blood samples, while in buccal swabs, five recipients showed no presence of donor-derived cells in their genotype. Epithelial cells swabbed from hand fingertips were not devoid of donor-derived cells since all recipients showed high chimerism (39.69%–96.66%) in their genotypes. A significant change in chimerism was seen among various types of biological samples (p<0.05). No correlations were observed between chimerism and recipient age, gender, or time after transplant (p> 0.05). The loci D21S11, D8S1179, and FGA were the most informative, whereas D13S317, Vwa, and TOPX were the least informative STR markers. We concluded that touch DNA from a person who has undergone a successful allogeneic HSCTs should not be considered as reliable evidence for human identifications. Therefore, necessary precautions must be taken to avoid false identification and miscarriage of justice.

Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCRαβ/CD19 Depletion in Nijmegen Breakage Syndrome.

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to malignancies. HSCT appears to cure immunodeficiency, but remains challenging due to limited experience in long-term risks of transplant-associated toxicity and malignancies. Twenty NBS patients received 22 allogeneic HSCTs with TCRαβ/CD19+ graft depletion with fludarabine 150mg/m2, cyclophosphamide 20-40mg/kg and thymoglobulin 5mg/kg based conditioning regimens (CRs). Twelve patients additionally received low-dose busulfan 4mg/kg (Bu group) and 10 patients (including 2 recipients of a second HSCT) treosulfan (Treo group) 30g/m2. Overall and event-free survival were 0.75 vs 1 (p =0.16) and 0.47 vs 0.89 (p =0.1) in the Bu and Treo groups, respectively. In the Bu group, four patients developed graft rejection, and three died: two died of de novo and relapsed lymphomas and one died of adenoviral hepatitis. The four living patients exhibited split chimerism with predominantly recipient myeloid cells and predominantly donor T and B lymphocytes. In Treo group, one patient developed rhabdomyosarcoma. There was no difference in the incidence of GVHD, viral reactivation, or early toxicity between either group. Low-dose Bu-containing CR in NBS leads to increased graft failure and low donor myeloid chimerism. Treo-CR followed by TCRαβ/CD19-depleted HSCT demonstrates a low level of early transplant-associated toxicity and enhanced graft function with stable donor chimerism.

High incidence of BK virus-associated hemorrhagic cystitis in children after second or third allogeneic hematopoietic stem cell transplantation.

BKV-HC is a serious complication of allogeneic HSCT. To characterize the incidence, risk factors, and clinical outcomes of post-HSCT BKV-HC, we retrospectively analyzed 112 patients who underwent one or more allogeneic HSCTs at our hospital between 2001 and 2017. Twenty underwent second or third HSCT thereafter. Ten patients developed BKV-HC at a median of 30days after HSCT. The 100-day cumulative incidences of grade 0-4 and grade 2-4 BKV-HC were 7.8% and 6.2%, respectively. HSCTs performed in 2011-2017 associated with significantly higher 100-day cumulative incidence of grade 2-4 BKV-HC (14.0%) than HSCTs performed in 2001-2010 (1.3%, P=0.004). On multivariate analysis, second or third HSCT was the only independent significant risk factor for development of grade 2-4 BKV-HC (P=0.015). Serial PCR monitoring of urine and blood BKV load did not predict BKV-HC. The recent increase in the incidence of BKV-HC may reflect recent innovations in transplant technologies that facilitate second or third HSCT, which are known to cause prolonged immune deficiency. If safe and effective treatment or prophylaxis becomes available, it could be used to target the high-risk patients for BKV-HC.

Risk of osteoporosis and pathologic fractures in cancer patients who underwent hematopoietic stem cell transplantation: a nationwide retrospective cohort study.

BackgroundLong-term data on post-hematopoietic stem cell transplantation (HSCT) osteoporosis and fracture are limited. This study evaluated the long-term risk of osteoporosis and fracture in cancer patients who underwent HSCT.ResultsThe incidence density rate of osteoporosis was 12.5 per 1000 person-years in the HSCT group, which was significantly higher than that in the non-HSCT group (5.65 per 1000 person-years) after adjustment for associated factors and consideration of competing risk factors (adjusted subhazard ratio, 1.48; 95% confidence interval, 1.06–2.07). The incidence density rate of fracture was 4.89 per 1000 person-years in the HSCT group, and the risk of fracture was 1.40 times higher in the HSCT group than in the non-HSCT group (95% confidence interval, 0.83–2.40). The vertebra was the most common site of fracture after HSCT (68.4%). The risk of osteoporosis and fracture significantly increased in post-HSCT patients with both hematological malignancies and solid tumors. Both autologous and allogeneic HSCTs increased the risk of osteoporosis, whereas only autologous HSCT recipients had an increased risk of fracture.Materials and MethodsThis nationwide retrospective cohort study analyzed data from Taiwan's National Health Insurance Research Database. We identified an HSCT group comprising 1040 cancer patients who underwent HSCT during 2000–2008 and a non-HSCT group comprising 4160 propensity score-matched cancer patients who did not undergo HSCT. All patients were followed up until the occurrence of osteoporosis; fracture; December 31, 2011; or withdrawal from the insurance program.ConclusionsHSCT recipients have an increased risk of osteoporosis.

Upper Gastrointestinal Acute Graft-Versus-Host Disease Adds Minimal Prognostic Value When Present in Isolation or in Addition to Grade I or Other Grade II-Defining GvHD Manifestations

The clinical syndrome of acute upper gastrointestinal graft-versus-host disease (UGI aGvHD) is historically seen in 13% of MRD transplants and in 31% of recipients developing acute GvHD (aGvHD). UGI aGvHD is classified as a Grade II manifestation in the modified consensus criteria and often treated with systemic immunosuppressive therapy. We undertook a review of the CIBMTR database to assess prognostic implications of and outcomes after UGI aGvHD both in isolation and when present with other manifestations of aGvHD.Methods: 8567 adult recipients of myeloablative allogeneic HSCTs receiving T-cell replete PBSC or bone marrow grafts from siblings, well- or partially-matched unrelated donors for AML, ALL, CML or MDS between 2000 and 2012 were analyzed. The primary outcome was survival; secondary outcomes were DFS, TRM, relapse, and cGvHD. Isolated UGI aGvHD: we performed individual pairwise comparisons between recipients with isolated UGI (iUGI) aGvHD and those with no aGvHD, Grade I, Grade II or Grades III/IV aGvHD without UGI symptoms. UGI aGvHD in Addition to Other aGvHD Manifestations: we performed pairwise comparisons between recipients with aGvHD of the same grade, with and without UGI involvement. Recipients with Grade II aGvHD were reclassified for analysis based on non-UGI manifestations. Diagnoses of UGI aGvHD did not require biopsy confirmation. Analyzed covariates included age, race, KPS score, malignancy, disease stage, time from diagnosis to transplant, graft source, HLA-matching, sex match, CMV status, GvHD prophylaxis, and year of transplant. Analyses were adjusted for effect of transplant center on outcomes. Given the number of comparisons, a p value <0.01 determined significance. Recipients without aGvHD included those experiencing early death; Kaplan-Meier and incidence curves were analyzed from time of aGvHD onset.Results: 251 centers contributed. Median age of recipients was 42 years (range, 18-72). 49% of recipients received stem cells from HLA-matched siblings, 38% from well-matched and 13% from partially-matched unrelated donors. 20% of donor/recipient pairs were female->male. 71% received PBSCs. Isolated UGI aGvHD: 229 individuals had iUGI aGvHD. MRD recipients with iUGI aGvHD had the same prognoses for OS, DFS, TRM, relapse and chronic GvHD as recipients with Grades 0, I or II aGvHD without UGI symptoms in pairwise comparisons. URD recipients with iUGI aGvHD had decreased TRM and trended towards improved OS and DFS compared to recipients with Grade II aGvHD without UGI involvement (HR 2.70, p=0.0021; HR 1.59, p=0.0166; HR 1.52, p=0.0294; Table, Figure 1). Outcomes of URD recipients with iUGI aGvHD were similar to those with Grades 0 or I aGvHD in pairwise comparisons. UGI aGvHD in Addition to Other aGvHD Manifestations: UGI involvement added no significant prognostic information to analyzed outcomes when present in addition to Grades I or II aGvHD of skin or hepatic/lower GI origin (Figure 2). If UGI symptoms were removed from grading, 229 recipients would be reclassified as No aGvHD; 196 recipients would be reclassified as Grade I. The percentage of recipients with Grades 0/I GvHD would increase from 55.7% to 60.1%.Conclusions: The presence of isolated UGI aGvHD imparted limited prognostic information after MRD or URD transplantation in terms of OS, DFS, TRM, relapse or chronic GvHD when compared to recipients without aGvHD or those with Grade I or II manifestations other than UGI. Defining isolated UGI aGvHD as a Grade II entity is not supported by this analysis. The presence of UGI aGvHD in addition to other Grade I or Grade II manifestations within a given recipient likewise had minimal prognostic impact on clinical outcomes after MRD or URD HSCT. Inclusion of UGI symptoms in the current aGvHD grading schema warrants re-evaluation in light of the results of this analysis. [Display omitted] [Display omitted] [Display omitted] DisclosuresAlousi:Therakos, Inc: Research Funding.

Absence of High-Dose Consolidation Courses and Low Numbers of Allogeneic HSCTs Did Not Affect Overall Optimistic Results in B-Cell Precursor Ph-Negative Adult ALL Patients Treated By Non-Intensive but Non-Interruptive ALL-2009 Protocol: Data of the Russian ALL Study Group

IntroductionIt is postulated that the improvement in the overall treatment outcome in adult Ph-negative ALL came from the implementation of more aggressive pediatric-like protocols and higher portion of allogeneic HSCT. Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the opposite approaches: less intensive but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933.Patients and MethodsThe ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks prd/dexa with 3 instead of 4 dauno/vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks-continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications- with 1 day HD MTX and with 1 d HD ARA-C, both with L-asp and 3 ds dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11),L>100). No central MRD monitoring was performed.Since Apr 2009 till June 2015 20 centers had recruited 168 BCP-Ph-negative ALL pts with a median age 28 years (15-54), 84f/84 m. Full cytogenetics was available in 67,3% (n=113), 43,4% of them (n=49) had normal karyotype (NK), 10% (n=9%) had no mitosis, 47,6% (n=54) - different abnormalities (hypoploid-1, hyperploid-12, t(11q23)/MLL-8, del11q23-2, t(1;19)-2, t(12;21)-1;others-28). 26,7% of pts (n=45) were in the standard risk (SR) group (WBC <30, EGIL BII-III, LDH < 2N; no late CR; t(4;11)-negative), 56,5% (n=95) - in the high risk (HR) group (WBC >30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive), 28 patients (n=16,8%) were not qualified by the risk. The analysis was performed in June 2015. 158 pts were available for analysis.ResultsCR rate in 158 available for analysis pts was 87,7% (n=139), induction death occurred in 9,1% (n=14), resistance was registered in 3,2% (n=5). The majority of CR pts (87,8%) achieved it after prephase (12,2%, n=17) and the 1st phase of induction (75,6%, n=105). Late responders constituted 12,2% (n=17). Allogeneic BMT was performed only in 9 of 144 patients who survived induction (6,2%).Totally 31 pts (22,3%) had relapsed. At 60 mo OS for the whole group constituted - 50%, DFS - 51.3%. In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d, PRD resistance) age (>30 y) became statistically significant for OS, DFS and relapse probability (RP) (pic.1), abnormal karyotype - for DFS (30% vs 68%, p=0,04) and RP (42% vs 19%, p= 0,04). In a multivariate analysis no common risk factors were significant.ConclusionsOur data demonstrate that the proposed treatment approach is rather effective. We believe that constant non-interruptive treatment without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that it should be very strict compliance of the pts to the protocol. All pts, mostly from the region hospitals who refused prolonged and constant treatment (~5%), relapsed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Acute graft‐versus‐host disease in pediatric allogeneic hematopoietic stem cell transplantation. Single‐center experience during 10 yr

a-GvHD may complicate allogeneic HSCT. In this retrospective single-center study, we evaluated incidence and risk factors of a-GvHD in 197 consecutive allogeneic pediatric HSCTs applying Glucksberg and NIH a-GvHD classifications. Among 179 eligible transplants, the cumulative incidence of grade 0-I a-GvHD was 48% and grade II-IV was 52%. None of the considered variables significantly influenced the incidence of grade II-IV a-GvHD. Malignancy and myeloablation were associated with an increased risk of classic a-GvHD (p < 0.01). Seventy-two percentage of children are alive, with a significant difference in OS and TRM between grade 0 and I vs. grade II and IV a-GvHD; this observation was reproduced in the non-malignant setting, while only a disparity in TRM was evidenced in children with malignancy. In our experience, the incidence of a-GvHD was similar, regardless of donor type. Myeloablation and malignant disease represented the only risk factors for classic a-GvHD. Our results highlight the need for a better prevention of this complication in the non-malignant setting.

Controversies in BMT for Lymphoma

In this supplement the authors have outlined some of the important recent advances and areas for future investigation that will shape our current and future treatments of DLBCL.With a better understanding of the biology of this distinct yet heterogeneous group of diseases, we will more precisely classify the disease that each patient has and develop specific treatments to improve the results of both initial and salvage therapy. Improved classification schemas and therapeutic interventions based on specific disease biology should then lead to more effective application of both autologous and allogeneic HSCTs for these patients. It is hoped that these approaches, coupled with maintenance therapies such as those that have prolonged survival after autologous HSCT for multiple myeloma, will enhance the curability of DLBCL as well.

Improved Survival in Patients with Refractory Cytopenias (Low Risk Myelodysplastic Syndrome - MDS) Treated with Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants (allo TCD-HSCTs),

Abstract 3831 Background:Controversy exists regarding optimal treatment for pts with MDS with low blast percentages. Benefits of early transplant versus transplant-related morbidity and mortality have been debated. With increased time to transplant, MDS pts are more likely to undergo increased numbers of blood transfusions, experience more cytopenias, and are at risk of disease progression. Transplant offers a cure for MDS, and advances in supportive care during and after transplantation have afforded better outcomes and increased numbers of older pts to undergo transplant. Depletion of mature T cells from allogeneic HSCTs decreases the incidence of GvHD and its associated morbidity and mortality. This study therefore evaluated outcomes of pts with refractory cytopenias with less than 5% marrow blasts, who underwent T-cell depleted HSCTs from matched or mismatched, related or unrelated donors at a single center. Patients and Methods:Between February 1982 and May 2010, 44 pts with refractory cytopenias(marrow blasts <5%) underwent alloTCD-HSCTs at MSKCC. Thirty pts had de novo MDS, 8 therapy-related, and 6 post aplastic anemia. Median age was 37 yrs (range 9.5–63.5). The MDS subtypes by WHO criteria were: refractory anemia (10), refractory anemia/cytopenia with ringed sideroblasts (2), and refractory cytopenia with multilineage dysplasia (32). Prognosis and risk categories at diagnosis in pts with de novo and post aplastic anemia were determined using 3 scoring systems. Prognosis by IPSS was: low risk (2), intermediate risk-1 (32), intermediate risk-2 (2), unknown (2 – no cytogenetic studies); by WPSS criteria: very low (1), low (12), intermediate (16), high (7), unknown (2); and by MDACC criteria in 34 pts: category-1 (lower risk) (6), category-2 (27), category 3-(1). All pts were severely cytopenic and/or transfusion or cytokine-dependent before alloTCD-HSCT. The median time from diagnosis to transplant was 0.6 years (range 0.11–7.87). Pts were conditioned for transplant with regimens that either included high dose TBI plus chemotherapy (26) or chemotherapy only but including IV busulfan (18). Anti-thymocyte globulin was given for rejection prophylaxis to 40 pts. HSCT donors were: siblings (24) or unrelated donors (20); 12 of the 44 donors were mismatched. Stem cell source was bone marrow (22) or GCSF-primed peripheral blood (22). T cells were removed ex-vivo from the bone marrow grafts with soybean lectin agglutinin and rosetting with sheep red blood cell (sRBC) and from the peripheral blood stem cell grafts by positive selection with a CD34 antibody (Isolex) followed by sRBC rosetting. No posttransplant immunosuppression was given. Results:Forty-one of the 43 pts evaluable for engraftment recovered ANC >500cells/uL at a median of 11d (range: 9–22). Two pts had primary graft failure, and 3 had secondary graft failure. Four of these pts underwent second transplants. Acute GvHD, grade 1–2, developed in 3 pts. Three additional pts developed grade 3 GvHD, 2 after DLI given for refractory opportunistic infections and 1 after a second unmodified transplant for graft failure. Chronic GvHD occurred in 3 pts, one of whom had received a second unmodified transplant for graft failure. As of May 2011, 16 pts have expired. Causes of death included: GvHD (5, including post DLI), infections (5), graft failure/poor graft function (3), regiment-related toxicity (2), and late death due to lung cancer (1). Twenty-eight pts are alive and doing well with a median survival of 2.8 years (range: 0.5–21.43). The 2-year and 5-year survivals are: 70.1% and 63.3%. Younger recipient age (<50), favorable MDACC score, chemotherapy only preparative regimen, and recent transplants (≥ 2000) indicated a better survival but differences did not reach statistical significance. Survival was not associated with etiology, HLA matching, source of stem cells, IPSS, or WPSS in this series of patients. Conclusion:Treatment of MDS pts with refractory cytopenias with alloTCD-HSCTs from matched and mismatched related and unrelated donors cures >60% of pts beyond 5 years, with a low incidence of acute and chronic GvHD. These findings support early transplant in the treatment of MDS with refractory cytopenias, especially in younger pts. Disclosures:Small:Pfizer, Inc: Equity Ownership, family member employed by Pfizer, Inc.

The EBMT activity survey 2007 with focus on allogeneic HSCT for AML and novel cellular therapies

The 2007 report describes the current status of HSCT activity in Europe, highlights the increasing role of allogeneic HSCT in treatment of AML and gives the first quantitative information on novel cellular therapies. In 2007, there were 25 563 first HSCTs, 10 072 allogeneic (39%), 15 491 autologous (61%) and 3606 additional transplants reported from 613 centers in 42 countries. The main indications were leukemias (8061 (32%; 89% allogeneic)); lymphomas (14 627 (57%; 89% autologous)), solid tumors (1488 (6%; 96% autologous)) and nonmalignant disorders (1302 (5%; 91% allogeneic)). Peripheral blood was the main source of stem cells for autologous HSCT (98%) and the predominant source for allogeneic HSCT (71%). Among allogeneic HSCTs, the number of unrelated donor grafts equaled the number of HLA-identical sibling donor grafts for the first time (47% each). AML was the most frequent indication for allogeneic HSCT (32% of all allogeneic HSCTs), with an increase of 247 (8%). Information on novel cellular therapies was collected for the first time; there were 212 mesenchymal SCTs and 212 HSCTs for nonhematopoietic use. The indications for the latter were cardiovascular disorders (97; 46%), neurological disorders (94; 44%) and tissue repair (21; 10%). These data illustrate the expanding role of cellular therapies.

Fever and neutropenia in pediatric hematopoietic stem cell transplant patients.

The objective of this study was to identify patterns of fever and neutropenia in pediatric patients undergoing initial hospitalization for hematopoietic stem cell transplantation. A retrospective review of 75 HSCTs over a 4-year period at a single institution was performed, of which 68% were allogeneic and 32% were autologous. Stem cell sources included bone marrow (29%), PBSC (52%) and umbilical cord blood (16%). Fever occurred in 74 (98%) of the episodes. Unexplained fever (FUO) occurred in 43%. Bacteremia without an anatomic focus occurred in 29%, while CVC associated infections occurred in 17%. In 49% of transplants at least one blood culture was positive. The incidence of bacteremia was higher in allogeneic HSCTs (58%) than in autologous transplants (29%). Gram-positive bacteria accounted for 71% of the isolates. Lower rates of bacteremia were observed in patients receiving oral fluoroquinolone prophylaxis. The median duration of fever was 12.5 days and time to engraftment 14 days. Regression analysis demonstrated that duration of fever was strongly associated with time to engraftment, and that time to engraftment was associated with source of cells and number of CD34+ cells/kg administered. Recipients of autologous PBSC had the shortest durations of fever and time to engraftment, while recipients of allogeneic umbilical cord blood had the longest. Bone Marrow Transplantation (2000) 25, 59-65.