Abo不相容性和抗a / B异凝集素滴度对血液恶性肿瘤清髓处理后输血需求和无关脐带血移植的早期结果的影响

Abstract Background:ABO incompatibility is not considered a main contraindication to allogeneic hematopoietic stem cell transplantation (aHSCT). However, it has been associated with a number of immunohematological complications. The effects of ABO incompatibility on aHSCT remain controversial.The change of isoagglutinin titers and early clinical outcomes were analyzed after unrelated cord blood transplantation (UCBT) with ABO-incompatibility donor. Methods:252 patients with hematological malignant diseases and other hematological disorders who underwent unrelated UCBT from January 2019 to April 2020 were retrospectively analyzed in this research. Patients were studied in identical, major, minor and bidirectional mismatch groups. Immunoglobulin m (IgM) isoagglutinin titers were tested one day before the transplant (-1 day), 2 weeks post-transplant, 4 weeks post-transplant and 6 weeks post-transplant. R esults:76 match,71 major mismatch, 70 minor mismatch and 35 bidirectional unrelated UCBT were identified. The median neutrophil, PLT and red blood cell (RBC) recovery days were 18, 38 and 22, respectively. ABO mismatch did not influence the neutrophil, PLT and RBC engraftment. The median of RBC transfusion in 30 days were 5 units and PLT were 6 units. There were no statisitcal difference in 0-30 days RBC and PLT transfusion after UCBT. 31-100 days transfusion was similar to in 30 days transfusion. No patients developed pure red cell anemia (PRCA). -1day IgM titers ≥1:16 did not develop higher risk of grade II-IV aGVHD when compared with titers≤1:8 group. However, we detected a marginal higher PLT transfusion in 30 days after transplant at antibody titers ≥1:16 group when compared with titers≤1:8 (P=0.051). In the major and bidirectional groups, we found that group O IgM anti-donor antibodies were displayed a significant higher than the group B anti-A titer (p<0.001) in setting the time one day before the transplant, but no significant with group A. 2 weeks after the transplant, group B anti-A was still showed significant lower than the group O anti-A (p<0.001). 4 weeks after the UCBT, we observed a modest, but no statistical significant lower titers of group B anti-A antibodies as compared with O group (P=0.097). 6 weeks after the transplant, there were no statistical significant among group O, A and B. In the multivariable Cox regression model, transfusion of ≥5 RBC units in 30 days after UCBT (HR=1.727, 95%CI=1.020-2.926, P=0.042) and PLT engraftment ≥38 days (HR=1.964, 95%CI=1.134-3.401, P=0.016) were correlated to greater risk of grade severe aGVHD. Conclusion:This study showed that ABO mismatch did not influence the neutrophil, PLT and RBC recovery time.Group O IgM anti-donor isoagglutinins in recepients showed a higher titers than the group B in setting with the time (-1 days pre-transplant, 2 weeks post-transplant, 4 weeks post-transpant). Pre-transplant higher anti-donor isoagglutinins were associated with more PLT transfusion requirements after UCBT. More RBC transfusion (≥5 units) and longer PLT recovery time (≥38 days) showed a higher incidence of severe aGVHD. Disclosures No relevant conflicts of interest to declare.

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Impact Of ABO Incompatibility On Overall Survival After Unrelated Cord Blood Transplantation a Single Institute Experience In China

Blood ◽

10.1182/blood.v122.21.5535.5535 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5535-5535

Author(s):

Sun Zimin ◽

Ji Mengmeng ◽

Yao Wen ◽

Zheng Changcheng ◽

Tong Juan ◽

...

Keyword(s):

Cord Blood ◽

Clinical Outcomes ◽

Conflicts Of Interest ◽

Cord Blood Transplantation ◽

Disease Free Survival ◽

Pure Red Cell Aplasia ◽

Blood Transplantation ◽

Abo Incompatibility ◽

Transfusion Requirements ◽

The Impact

Abstract Umbilical cord blood transplantation (UCBT) has now become a more common treatment for patients with hematologic malignancies who lack matched related or unrelated donors. However, few reports have addressed the impact of ABO incompatibility on the clinical outcomes, such as engraftment, transfusion requirements and survival after UCBT. Therefore, we retrospectively analyzed the impact of ABO mismatching on the clinical outcomes of 121 patients, including 51 ABO-identical, 23 minor, 39 major, and 8 bidirectional ABO-incompatible recipients after UCBT. With a median follow-up of 11 months (range, 5-151 months), the disease-free survival (DFS) rates among the ABO-identical, minor, major, and bidirectional ABO-incompatible groups were 71.7%, 60.0%, 37.1%, and 71.4%, respectively (P=0.014), whereas the OS did not differ significantly among the four groups (76.1%, 65.0%, 48.6%, and 71.4%, respectively; P=0.078). The DFS (68.2%, 42.9%; P=0.009) and OS estimates (72.7%, 52.4%; P=0.031) of the ABO identical/minor incompatible group also differed significantly from the ABO major/bidirectional incompatible group. These results were confirmed in the multivariate analysis. No signiﬁcant differences in the engraftment times, transfusion requirements, graft-versus-host disease (GVHD), relapse, and non-relapse mortality (NRM) were noted among the groups. Severe immune hemolysis or pure red cell aplasia did not occur among these patients. These results indicate that ABO incompatibility somewhat affects the DFS and OS in UCBT, but further studies are still required. Disclosures: No relevant conflicts of interest to declare.

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Transplantation of Maternal Haploidentical TcRαβ-Depleted Stem Cells for Malignant Infantile Osteopetrosis – Optimal Timing and Rapid Hematological Recovery

Blood ◽

10.1182/blood.v124.21.5935.5935 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5935-5935

Author(s):

Cornelis J.H. Pronk ◽

Dominik Turkiewicz ◽

Josefina Dykes ◽

Jacek Toporski

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Cord Blood Transplantation ◽

Conditioning Regimen ◽

Mixed Chimerism ◽

Common Mutation ◽

Impaired Hearing ◽

Hematopoietic Stem ◽

Post Transplant

Abstract BACKGROUND: Osteopetrosis (OP), characterized by improper bone resorption is in most cases caused by dysfunctional, hematopoietic stem cell (HSC) derived osteoclasts. A number of genetic mutations are described to underlie OP and disease phenotypes varies from benign to very severe, rapidly progressive forms of OP. In most cases hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Especially in infantile malignant OP early HSCT is critical in means to recover allogeneic osteoclast function to inhibit and prevent otherwise mutilating disease progression. The use of an alternative donor is required in the absence of an HLA-identical healthy sibling. While donor search is time consuming, umbilical cord blood transplantation is usually related to higher transplant related morbidity/mortality. We present a case of infantile malignant autosomal recessive OP that illustrates the advantage of the use of haploidentical maternal TcRαβ+ cells depleted graft as an attractive curative approach. PATIENT: The boy, carrying a common mutation involving the TCIRG1 gene was diagnosed with OP at 3 months of age while showing signs of progressing anemia, hypogammaglobulemia, esotropia/exophthalmia with suspicion of blindness, impaired hearing and multiple skeletal malformations. Three weeks later conditioning regimen was initiated and consisted of ATG-F (30mg/kg), i.v. busulfan (TDM; AUC 90mg +/- 5mg/L*h) fludarabin (160mg/m2) and thiotepa (15mg/mg). Maternal G-CSF mobilized mononuclear cells were harvested from peripheral blood and TcRαβ+ cell were depleted from the graft (CliniMACS). The patient was transplanted with a single graft including 44.8x106 CD34+ cells/kg, 48.6x106 TcRγδ+ cells/kg and 0.0011x106 of residual TcRαβ+ cells/kg, followed by post-transplantation in vivo CD20-depletion (Rituximab 375mg/m2). Platelets (>50x109/L) and neutrophils (>0.5x109/L) recovery was reached day +14, respectively day +15 post-HSCT. Immunosuppression consisted of Cyclosporine A and Methylprednisolon and was discontinued 4, respectively 6 weeks post-HSCT without any signs of GvHD. There was no significant transplant related morbidity. OP characteristics did not show obvious progression following HSCT and at one year post-transplant the patient is in a stable general condition with good quality of life. He has decreased but stable hearing performance, deeply impaired vision (already before HSCT), normalization of the phenotypic facial and skeletal characteristics, normal bone marrow function as well as normal physical and mental development. T-cell chimerism showed convertion from initially mixed chimerism (up to 40% of autologous cell) to 100% donor chimersim at 1 year post transplant. CONCLUSION: We conclude that haploidentical HSCT with TcRαβ+ depleted graft is an encouraging approach in infantile malignant OP that enables 1) prompt HSCT with immediate available parental donor and 2) rapid and sustained hematological recovery. Disclosures No relevant conflicts of interest to declare.

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Telomere Length Plays No Role in Clinical Unit Dominance After Double-Unit Cord Blood Transplantation

Blood ◽

10.1182/blood.v120.21.4661.4661 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4661-4661

Author(s):

Beth Ashbridge ◽

Ahmet Zehir ◽

Lingbo Shen ◽

Juliet N Barker ◽

Malcolm A.S. AS Moore

Keyword(s):

Cord Blood ◽

Telomere Length ◽

Mononuclear Cells ◽

Conflicts Of Interest ◽

Cord Blood Transplantation ◽

Length Variation ◽

Alternative Source ◽

Hematopoietic Stem ◽

Post Transplant ◽

Percentage Loss

Abstract Abstract 4661 Background: Umbilical cord blood (CB) is an alternative source of allogeneic hematopoietic stem cells for transplantation and has the advantage of a reduced stringency of the required human leukocyte antigen-match. It is limited, however, by low total nucleated cell (TNC) dose and a low progenitor number in single CB units, thus restricting the use of CB transplantation (CBT) in larger children and adults. One strategy to augment engraftment is to combine 2 units from 2 different donors in a double-unit graft. We have previously shown that in most cases, one unit emerges as the sole source of hematopoiesis long-term, but as yet the mechanism of unit dominance remains unknown (Blood, 2010, 116(19):3999–4006). CB units are known to have an inherent biological variation in telomere length, the repeat sequence capping the ends of chromosomes. Telomere length variation and progressive shortening of telomere could later hematopoietic potential. Methods: We evaluated if telomere length has a role in unit dominance and how telomere length progresses over time post-transplant. We purified mononuclear cells from small aliquots of each unit of double-unit grafts and post-transplant peripheral blood (days +28, 100, 180 and 1 year) in 12 adult double-unit CBT recipients transplanted for hematologic malignancies at MSKCC. Average telomere length was measured using the TeloTTAGGG Telomere Length Assay (Roche) which utilizes Southern analysis of terminal restriction fragments (TRF) that are obtained by the digestion of isolated genomic DNA. Results: All 12 patients engrafted with one unit showing predominance. While there was a range of telomere length (5.57–12.09 kb) in the 24 units evaluated on the day of transplant, when comparing the telomere length of engrafting to non-engrafting units, there was no association between telomere length at day 0 and subsequent unit dominance. In 5 patients the engrafting unit had longer telomeres and in 7 patients the non-engrafting unit had longer telomeres. In serial assays, 7 of 12 patients demonstrated telomere length stabilization post-transplant in the dominant unit with a mean percentage loss of telomere length of 7.15% ± 2.33%. A second group (n = 5) demonstrated a decrease in telomere length with a mean percentage loss of 29.48% ± 5.12%. While this difference is significant (p = 0.0015) the clinical significance of this finding is uncertain. We are currently following these patients in order to correlate telomere length (stabilization versus decrease) with clinical outcomes. Conclusions: This data suggests that unit dominance is not influenced by telomere length. It is likely, based on emerging data from our laboratory as well as others, that unit dominance is immune mediated. However, the influence of telomere length on the quality of engraftment is of interest and analysis of this is ongoing with larger numbers of patients required to also consider the infused cell dose. It is notable that 7/12 patients had telomere length stabilization which correlates with the high levels of telomerase activity previously reported in the in vitro expansion of CB (Blood, 2004, 103(12):4440-8). Disclosures: No relevant conflicts of interest to declare.

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Graft-versus-host disease and donor-directed hemagglutinin titers after ABO-mismatched related and unrelated marrow allografts: evidence for a graft-versus-plasma cell effect

Blood ◽

10.1182/blood.v96.3.1150 ◽

2000 ◽

Vol 96 (3) ◽

pp. 1150-1156 ◽

Cited By ~ 94

Author(s):

Marco Mielcarek ◽

Wendy Leisenring ◽

Beverly Torok-Storb ◽

Rainer Storb

Keyword(s):

Plasma Cell ◽

Graft Versus Host Disease ◽

Plasma Cells ◽

High Dose ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Abo Incompatibility ◽

Transfusion Requirements ◽

Gradual Disappearance

Abstract The gradual disappearance of host antidonor isohemagglutinins after major ABO-mismatched hematopoietic stem cell (HSC) allografts has been attributed to the gradual destruction of host plasma cells by graft-versus-host effects. To corroborate this hypothesis, we retrospectively analyzed results from 383 major or major/minor ABO-mismatched unrelated and related HSC allografts performed between 1983 and 1998. All patients were conditioned by high-dose pretransplant therapy and given methotrexate/cyclosporine for graft-versus-host disease (GvHD) prophylaxis. Of the 383 patients, 155 had HLA-matched related and 228 had unrelated grafts. We asked whether unrelated recipients experienced a more rapid disappearance of isohemagglutinins than related recipients, and whether, within the groups of related and unrelated recipients, the titer disappeared faster in patients with GvHD than in those without GvHD. The median time to reach undetectable antidonor IgG and IgM titers was significantly shorter in unrelated recipients (46 versus 61 days; P = .016). In addition, related recipients with GvHD had a 2.2-fold increased likelihood (1.12-4.39,95% CI; P = .02) of reaching undetectable titers within 100 days than patients without GvHD. The persistence of antidonor isohemagglutinins led to significantly increased red blood cell (RBC) transfusion requirements in the ABO-mismatched related patients compared with ABO-matched counterparts. However, time to neutrophil and platelet engraftment, incidence of GvHD, and survival were not influenced by ABO incompatibility. In conclusion, our results corroborate the hypothesis that the rate of disappearance of antidonor isohemagglutinins after ABO-mismatched allogeneic HSC grafts is influenced by the degree of genetic disparity between donor and recipient, suggesting a graft-versus-plasma cell effect.

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HHV-6 Encephalitis in Pediatric Unrelated Umbilical Cord Blood Transplantation: Role for Ganciclovir Prophylaxis?

Blood ◽

10.1182/blood.v114.22.4667.4667 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4667-4667

Author(s):

Frankie Wai Tsoi Cheng ◽

Vincent Lee ◽

Wing Kwan Leung ◽

Paul Kay Sheung Chan ◽

Ting Fan Leung ◽

...

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Conflicts Of Interest ◽

Rare Complication ◽

Cord Blood Transplantation ◽

The Other ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Before And After

Abstract Abstract 4667 Background The role of ganciclovir as HHV-6 prophylaxis in unrelated hematopoietic stem cell transplant (HSCT) setting remains controversial. Methods We performed a 8-year retrospective review of patients received unrelated HSCT from January 2000 to September 2008. From January 2002, ganciclovir prophylaxis 5mg/kg twice daily for 7 days for all unrelated HSCT before transplant was adopted. The other transplant policies including antibacterial, antifungal, antiviral and graft-versus-host disease control policies remained unchange in that period. The prevalence of HHV-6 encephalitis was studied before and after the change in policy. Result Fifty-four unrelated HSCT were performed from January, 2000 to September, 2008. Total four cases (7.4%) of HHV-6 encephalitis were diagnosed. Two cases out of 16 cases (12.5%) diagnosed before adoption of the policy; 2 cases out of 38 cases (5.3%) diagnosed afterward. All of them were unrelated umbilical cord blood (UCB) transplant recipients. Two cases had significant residual neurological deficit and refractory seizure. The other two cases died of other transplant-related mortalities. Conclusion We conclude that HHV-6 encephalitis is still a rare complication of unrelated HSCT and may be more common in unrelated UCB transplantation. Routine use of ganciclovir as HHV-6 prophylaxis in all unrelated HSCT recipients may not be justified. Disclosures: No relevant conflicts of interest to declare.

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A Randomized Comparison of Standard Weekly Epoetin Alfa to Every-3-Week Epoetin Alfa and Every-3-Week Darbepoetin Alfa: A Study of the Mayo Clinic Cancer Research Consortium (MCCRC).

Blood ◽

10.1182/blood.v114.22.3008.3008 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3008-3008 ◽

Cited By ~ 1

Author(s):

David P Steensma ◽

Shaker R. Dakhil ◽

Paul J Novotny ◽

Jeff A Sloan ◽

David B Johnson ◽

...

Keyword(s):

Primary Endpoint ◽

Darbepoetin Alfa ◽

Conflicts Of Interest ◽

Fixed Dose ◽

Weekly Schedule ◽

Epoetin Alfa ◽

Transfusion Requirements ◽

Significant Difference ◽

Distress Scale ◽

Rbc Transfusion

Abstract Abstract 3008 Poster Board II-984 Introduction: The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients (pts) with cancer chemotherapy-associated anemia (CAA). Extended-interval ESA dosing (i.e., administration less than once weekly) is a common practice with DA, which is FDA approved for dosing once every 3 weeks (q3wks); a previous study of the North Central Cancer Treatment Group suggested that EA can also be given less often than the FDA-approved once weekly schedule (Steensma DP et al, J Clin Onc 2006; 24:1079). The present study compared 2 different q3wks extended-interval EA regimens with weekly fixed-dose EA and with q3wks DA in pts with CAA. Patients and Methods: Eligible pts were receiving chemotherapy for a non-myeloid malignancy and had Hb <10.5 g/dL, ferritin >20 ng/mL, weight >40 kg and <150 kg, and ECOG performance score £2. Pts were randomized 1:1:1:1 to receive EA 40,000 Units subcutaneously (SC) once weekly (40K arm), EA 80,000 Units SC q3wks (80K arm), EA 120,000 Units SC q3wks (120K arm), or DA 500 mcg SC q3wks (DA arm), for 15 weeks. EA and DA were held for Hb >12 g/dL and restarted at a lower dose when Hb fell to '11.5 g/dL. All pts received ferrous sulfate 325 mg orally once daily, if tolerated. Quality of life (QOL) was measured using the Symptom Distress Scale (SDS), Brief Fatigue Inventory (BFI), FACT-An, and Linear Analogue Self Assessment (LASA) tools. The primary endpoint was the proportion of pts achieving Hb≥11.5 g/dL or increment of Hb>2.0 g/dL from baseline. Secondary endpoints included RBC transfusion requirements, adverse events (AEs), and QOL. Results: 239 pts (236 evaluable) enrolled at 10 MCCRC sites between Feb. 2007 and Dec. 2008; 62% of pts completed all study interventions. The median age of enrolled pts was 66 years; 42.4% were men, 91.5% had solid tumors, 26.7% had severe anemia (Hb <9.5 g/dL), and 44.9% were receiving platinum-containing regimens. Baseline characteristics were balanced between study arms, with the exception of gender (39% female for 40K, 60% for 80K, 43% for 120K, 26% for DA). There were no significant differences between treatment arms in the proportion of pts achieving a Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; p>0.41 for all comparisons), but the median Hb increment from baseline was higher in the 40K and DA arms compared to the 2 extended dosing EA arms (40K-2.8 g/dL, 80K-2.0 g/dL, 120K-2.1 g/dL, DA-2.6 g/dL; p=0.005 for 40K vs 80K). Hb response was achieved more quickly in the weekly EA arm, but the difference was not significant (40K-32 days, 80K-50 days, 120K-49 days, DA-49 days; p>0.13). The proportion of patients transfused was similar between arms (40K-27.9%, 80K-33.3%, 120K-22.4%, DA-29.8%; p>0.49). There were no significant differences in QOL changes. Deaths were also similar between arms (40K-5 pts, 80K-7 pts, 120K-7 pts, DA-1 pt, p>0.10) and were primarily due to disease progression. AEs and serious AEs were comparable between study groups; grade 3/4 AEs were observed in 22% of pts in the 40K arm, 22% on 80K, 17% on 120K, and 13% on DA; p>0.56. The median total dose of EA used was highest in the 120K arm (40K-265,000 U; 80K-240,000 U; 120K-360,000 U; p=0.0009 for 40K vs 120K), while pts on the 40K arm were more likely to omit a dose due to a high Hb (40K-63.9% of pts omitted at least one dose; 80K-30.0%; 120K-34.5%; DA-43.6%, p<0.0001 for 40K vs 80K). Conclusion: Although there was no significant difference in the proportion of responding pts (the primary endpoint), Hb increments from baseline were moderately higher with the 2 FDA-approved regimens – weekly EA 40,000 Units, and q3wk DA 500 mcg – than with the extended dosing regimens. This study was supported by a grant from Centocor Ortho Biotech, Inc. to the MCCRC. Disclosures: No relevant conflicts of interest to declare.

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Vaccine Response In Recipients of HLA Mismatched Unrelated Double Unit Cord Blood Transplantation (CBT).

Blood ◽

10.1182/blood.v116.21.1247.1247 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1247-1247 ◽

Cited By ~ 1

Author(s):

Trudy N Small ◽

Christine Scura Iovino ◽

Michelle Abboud ◽

Marissa Lubin ◽

Esperanza Papadopoulos ◽

...

Keyword(s):

Hepatitis B ◽

B Cell ◽

Conflicts Of Interest ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Optimal Schedule ◽

High Dose ◽

Vaccine Response ◽

Post Transplant ◽

History Of

Abstract Abstract 1247 The use of CBT has increased steadily over the last decade, with recent studies showing long-term progression-free survival similar to that of unrelated volunteer donor transplant recipients. The ability of CBT survivors to respond to post-transplant immunizations may differ from other allogeneic transplant populations due to the lack of transfer of memory T- and B-cells with the graft. Limited data have been reported on vaccine responses following this treatment modality. We, therefore, analyzed responses to immunizations in 23 double-unit CB recipients (17 adults, 6 children) transplanted at our center from 10/05-12/08. Patients were transplanted at a median age of 34 years (range 7–61) for the treatment of acute leukemia (n=13), or lymphoma/CLL (n=8/2). They received high-dose myeloablative (n=11), reduced intensity myeloablative (n=5), or non-myeloablative (n=7) conditioning according to diagnosis, age, prior therapy, and co-morbidities. GVHD prophylaxis consisted of a calcineurin inhibitor and mycophenolate mofetil. No patient received ATG. The study patients had sustained engraftment with a 5/6 (n=12) or 4/6 (n=11) HLA-matched unit. Seven recipients received rituximab (median 4 doses, range: 4–8) as planned post-transplant therapy for B-cell malignancies (n=6) or treatment of an autoimmune hemolytic anemia (n=1). Eleven patients had a history of grade II-IV acute GVHD and 5 had ongoing late acute or chronic GVHD prior to vaccination. Criteria for vaccination were: CD4 cell count of at least 200 cells/ul, PHA of greater than 60% lower limit of normal and serum IgG level >500 mg/dl at least 6 weeks following the last dose of IVIG. The median time to vaccination was 1.26 years post-CBT; this time was significantly longer in patients treated with Rituximab compared to those who were not (1.6 years versus 1.2 years, p=0.02), due to delayed normalization of B-cell numbers in the former group (449 days vs 108 days, p=0.004).Pre-vaccination titers obtained at a median of 1 year post-CBT demonstrated that over 85% of patients lacked protection against Pneumococcus, H. influenzae, and Pertussis, and at least 50% lacked immunity against tetanus, measles, and mumps. Seroconversion or >3- fold rise in titer was observed in response to tetanus, diphtheria, H. influenzae, and Pneumococcus in 90% (18/20), 81% (13/16), 80% (16/20)and 90% (18/20) of patients and was not significantly different in patients with or without a history of acute or chronic GVHD. Whereas 90% (5/6) of patients without a history of GVHD responded to a series of Hepatitis B immunizations, only 22% (2/9) of those with prior acute and/or chronic GVHD did so (p=0.03). No patient was protected against pertussis following a single TDaP (n=14) and only 1 of 5 patients responded to the protein conjugated meningococcal vaccine. Immunization with a live attenuated vaccine was initiated in 7 seronegative patients, including all 6 children, at a median of 2.25 years (range 1.5–3.6) post-CBT (MMR, n=7, Varivax, n=3). Seroconversion against measles, mumps, rubella, or chickenpox was observed in 3/7, 2/7, 6/7, and 1/3 patients, respectively. There were no serious reactions to any vaccine. These data suggest that CBT recipients are capable of responding to tetanus, diphtheria, H. Influenza and pneumococcal vaccines similar to other transplant groups. Nonetheless, the sub-optimal response to pathogens associated with outbreaks in the community (Hepatitis B, Pertussis, meningococcus, measles, mumps, varicella) highlight the need to obtain pre- and post-vaccination titers to document response, as well as define the optimal schedule of post-transplant immunizations specifically in this transplant population. Disclosures: No relevant conflicts of interest to declare.

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DynaChip Anti-HLA Antibody Analysis In Sera of Patients Following Allo-HSCT From HLA-Mismatched Unrelated Donors.

Blood ◽

10.1182/blood.v116.21.4575.4575 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4575-4575

Author(s):

Miroslaw Markiewicz ◽

Urszula Siekiera ◽

Tomasz Kruzel ◽

Monika Dzierzak-Mietla ◽

Patrycja Zielinska ◽

...

Keyword(s):

Conflicts Of Interest ◽

Hla Class I ◽

Class I ◽

Hla Antibodies ◽

Hematopoietic Stem ◽

Post Transplant ◽

Study Results ◽

Reactive Groups ◽

Unrelated Donors ◽

Class Ii Antigens

Abstract Abstract 4575 Introduction: Anti-HLA antibodies constitute potentially important factor that may influence outcomes of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT). The rationale of this study was to detect presence of anti-HLA antibodies in recipients of allo-HSCT from HLA-mismatched unrelated donors. Patients and Methods: Anti-HLA-A,B,C,DR,DQ,DP antibodies were identified in sera collected from 46 recipients of allo-HSCT from HLA-mismatched unrelated donors. Sera were collected between 1 month and 5.5 years after allo-HSCT, and additionally before allo-HSCT in 17 pts. We have used microchips spotted with purified HLA class I and HLA class II antigens to allow binding of anti-HLA antibodies present in tested sera to the surface of the microchip, pre-optimised reagents and DynaChip Processor (Dynal Invitrogen Corporation) for assay processing, data acquisition and analysis. Results: Antibodies against HLA class I, II or I and II were detected in 15%, 11% and 35% of pts whereas no antibodies were detected in 39% of patients. Antibodies were directed against HLA-A, B, C, DR and DQ in 37%, 46%, 35%, 48% and 35% of pts, respectively. Pre-transplant anti-HLA antibodies have been detected in 7 pts (41%) out of 17 tested before allo-HSCT. In this group percent of Panel Reactive Antibodies (% PRA) increased following allo-HSCT in 3 pts and decreased in 4. In 5 out of 10 remaining pts without pre-transplant antibodies, %PRA increased post-transplant. DynaChip software allowed to define specificities of HLA-A,B,C,DR and DQ antibodies on low and high resolution levels. The specificity of antigens that masked results of antibody identification has been also defined in 2 pts. At this stage we did not define exactly whether detected anti-HLA antibodies were donor-specific. Cross-reactive groups (CREG's) analysis has been also used to compare antibodies’ reactivity. Anti-HLA-DP antibodies were not detected in the examined group of transplanted patients. Conclusions: Presented preliminary study results indicate, that anti-HLA antibodies can appear post-transplant in mismatched allo-HSCT recipients. Further analysis aiming to evaluate their influence on transplant outcomes is ongoing. We intend to extend the search for anti-HLA antibodies with use of Luminex LabScreen method. Disclosures: No relevant conflicts of interest to declare.

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A Brief Use of Imatinib Immediately Before Hematopoietic Stem Cell Transplantation (HSCT) in Children with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL). Results of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph+ALL04

Blood ◽

10.1182/blood.v118.21.2554.2554 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2554-2554

Author(s):

Atsushi Manabe ◽

Hirohide Kawasaki ◽

Motoaki Chin ◽

Atsushi Sato ◽

Kimikazu Matsumoto ◽

...

Keyword(s):

Survival Rate ◽

Medical Information ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Cord Blood Transplantation ◽

High Dose ◽

Induction Phase ◽

Study Group ◽

Pediatric Leukemia ◽

Hematopoietic Stem

Abstract Abstract 2554 Aims: Children with Ph+ALL generally have a poor prognosis when treated with chemotherapy alone. The timing and duration of the use of imatinib has not been determined. We investigated a role of imatinib immediately before HSCT. Methods: All the patients with ALL were screened for diagnosis of Ph+ALL using RT-PCR. Children with Ph+ALL were enrolled on JPLSG Ph+ALL04 Study within 1 week of initiation of treatment for ALL. Treatment regimen consisted of 5 therapeutic phases: Induction phase (5-drug induction), Intensification phase (high-dose cytarabine and BFM Ib), Re-induction phase (4-drug re-induction), 2 weeks of Imatinib monotherapy phase (23 weeks after diagnosis), and HSCT phase (Etoposide+CY+TBI conditioning). Before and after each phase, minimal residual disease (MRD), the amount of BCR-ABL transcripts, was measured with the real-time PCR method (cut-off 50 copies/microgram RNA). The study was registered in UMIN-CTR (Medical Information, University hospital Medical Information Network - Clinical Trials Registry): UMIN ID C000000290. Results: During the period 2004–08, 42 patients were registered in the Ph+ALL04 study. Out of 42 patients, 37 patients (88%) achieved CR and 7 of 37 patients also achieved MRD-negative after induction phase. There were 13 patients who had no MRD at the beginning of imatinib monotherapy phase, and 14 patients were MRD-negative after imatinib phase, consequently, 14 patients were MRD-negative at the time of HSCT. Six patients relapsed before HSCT. In total, 31 patients received HSCT in 1st CR. All the patients had engraftment and no patients died because of complications of HSCT. Five patients relapsed after HSCT and 4 of the 5 patients were MRD-negative before HSCT and the other patient had detectable MRD although it was less than 50 copies. Twenty-six patients continue to be in 1st CR and MRD-negative for median of 3 years after diagnosis. The 3-year event-free survival rate and over-all survival rate for all the patients was 57% and 80%, respectively (figure 1). Five patients did not achieve CR after induction phase and they were treated with imatinib-contained chemotherapy. Four of the 5 patients achieved CR. All of the 4 patients received cord blood transplantation and remains in continued CR. Interpretation: The chemotherapy we employed was based on the previous high-risk regimen of TCCSG (Tokyo Children's Cancer Study Group) L-99-15 Study. The chemotherapy was intensive enough to induce MRD-negative in 13 at the time of imatinib phase and 31 of 42 patients were in CR at the time of HSCT (around 25–28 weeks after diagnosis). We planned to assess the efficacy of imatinib immediately before HSCT but it was not possible because of the low amount of MRD in most patients at the beginning of imatinib phase. Conclusion: Although EFS and OS was excellent in this study, 88% of induction rate appeared unsatisfactory and relapse occurred before HSCT in 6 out of 37 patients who achieved CR after induction phase. Earlier and longer use of imatinib may improve EFS in children with Ph+ALL and HSCT may be omitted in a subset of patients who achieve an early and deep remission status. Disclosures: No relevant conflicts of interest to declare.

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The Favorable Results of Allo-HSCT in TKI-Resistant CML,

Blood ◽

10.1182/blood.v118.21.4145.4145 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4145-4145

Author(s):

Miroslaw Markiewicz ◽

Monika Dzierzak-Mietla ◽

Katarzyna Wisniewska-Piaty ◽

Andrzej Frankiewicz ◽

Anna Koclega ◽

...

Keyword(s):

Conflicts Of Interest ◽

Therapeutic Option ◽

Hemorrhagic Cystitis ◽

Chronic Gvhd ◽

Hla Antigens ◽

Mixed Chimerism ◽

Hematopoietic Stem ◽

Post Transplant ◽

Advanced Phase ◽

Tki Treatment

Abstract Abstract 4145 Introduction: Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML). However, for patients who fail TKI or progress to advanced phase disease, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only therapeutic option. The rationale of this study was to evaluate results of allo-HSCT in CML patients who have failed TKI treatment. Patients and Methods: 48 CML pts aged 33 (19–52) years who failed previous treatment with TKI (imatinib-37 pts, imatinib+dasatinib-5, imatinib+dasatinib+nilotinib- 3, dasatinib-2, imatinib+nilotinib-1) received allo-HSCT from HLA-matched siblings (15) or from 10/10 (21) and 9/10 (12) HLA-antigens-Matched Unrelated Donors (MUD) in Hematology and BMT Center in Katowice, Poland, from 10.2002 to 03.2011. The myeloablative preparative regimen consisted of treosulfan 3×14 g/m2 plus fludarabine 5×30 mg/m2 (30 pts) or busulfan 4×4 mg/kg plus cyclophosphamide 4×30 mg/kg (18 pts). Standard GVHD prophylaxis consisted of cyclosporine-A, methotrexate and pre-transplant ATG or thymoglobulin in allo-HSCT from MUD. Source of cells was bone marrow (27 pts) or peripheral blood (21 pts) with median 2.6 or 6.7 x10(6)CD34+cells/kg, respectively. Results: All pts engrafted. 100% donor chimerism has been achieved in 40 (83.3%) pts, 97–99% in 4 pts, progressing mixed chimerism was observed in 4 pts. The 5-year estimated overall survival rate was 79%. 9 pts died 9 (1–21) months following allo-HSCT due to infection (5), GVHD (3) or relapse (1). Bio-molecular relapse or progressing mixed chimerism was observed in 6 pts and was treated with 3 to 5 donor lymphocyte infusions (3 pts), post-transplant imatinib (3 pts) or nilotinib (1 pt). Acute GVHD grade I, II, III and IV was observed in 15, 13, 2 and 1 pt (serious aGVHD grade III-IV in 3 pts (6.25%) only); limited and extensive chronic GVHD in 17 (35.4%) and 9 (18.75%) pts, respectively. Other complications in survivors included CMV reactivation (12), hemorrhagic cystitis (3), H. zoster (2), P. jiroveci (1) and cataract requiring surgery (1). 39 pts (81.25%) are alive 44 (3–92) months post-transplant. Conclusions: Allo-HSCT with myeloablative treo/flu or bu/cy conditioning is a feasible and effective curative therapy in TKI-resistant CML. The alternative therapy with allo-HSCT may overcome TKI resistance, providing long-term remission or cure from CML in patients who failed TKI treatment. Disclosures: No relevant conflicts of interest to declare.

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