Gemtuzumab Ozogamicin After Allogeneic Stem Cell Transplantation for Acute Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1970-1970
Author(s):  
Takeshi Kobayashi ◽  
Naoki Shingai ◽  
Shuntaro Ikegawa ◽  
Yukie Takahashi ◽  
Jun Aoki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Conflicts Of Interest ◽  
Initial Response ◽  
Disease Recurrence ◽  
Gemtuzumab Ozogamicin ◽  
Hematopoietic Stem

Abstract Abstract 1970 Abstract Controversy abounds that anti-CD33 immunoconjugate, genutuzumab ozogamicin (GO) is really effective or not as a treatment for relapsed acute myeloid leukemia (AML). Consequently, GO is now commercially available in Japan, but not in USA or Europe. In this study, we have retrospectively analyzed the clinical impact of GO therapy as salvage or maintenance setting after allogeneic hematopoietic stem cell transplantation (allo-HSCT). During last 5 years, GO was given to 19 patients with AML as salvage therapy for disease recurrence (n = 15 patients) or maintenance therapy (n = 4 patients) after allo-HSCT in our institution. Clinical characteristics of these 19 patients are summarized (see Table): Median age was 44 years (range, 21–70 years). GO was basically administered at a dose of 3 mg/m2. The median cycle of GO therapy was 3 cycles (range, 1–12 cycles) and 3 cycles (range, 1–4 cycles) as salvage and maintenance therapy, respectively. GO was administered at a median of 205 days after allo-HSCT (range, 38–3,111 days) in the setting of salvage therapy, while as maintenance therapy, patients with high risk AML received GO as early as 29 days after allo-HSCT (range, 24–71 days). Two of 15 patients with recurrent disease achieved complete remission and 4 patients showed partial response (>50% decrease of bone marrow blast percentage). Thus, a total of 6 patients (40%) exhibited initial response to GO. However, 5 patients of them developed irreversible hepatic veno-occulusive disease (VOD) and eventually died at median of 146 days after GO therapy (range, 9–206 days). In view of 4 patients with maintenance therapy, 1 patient have faced to the subsequent disease relapse but no patients developed severe adverse effects including hepatic VOD and all patients are currently alive, albeit short follow-up. This small study demonstrates that GO offers an alternative tool for rescuing relapsed AML after allo-HSCT, but increases the risk of developing life-threatening hepatic VOD. Thus, further clarification is needed regarding which patients to treat with GO and at what dose of GO. Disclosures: No relevant conflicts of interest to declare.

Long-Term Clinical Outcome of Children with Acquired Aplastic Anemia in Brazil.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4216-4216
Author(s):  
Marlene Pereira Garanito ◽  
Vicente Odone Filho ◽  
Marcela Vieira dos Santos ◽  
Elvira Velloso ◽  
Frederico L. Dulley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Cell Transplantation ◽  
Survival Probability ◽  
Conflicts Of Interest ◽  
Time History ◽  
Hematopoietic Stem ◽  
Significant Difference

Abstract Abstract 4216 Introdution/ Backgound Acquired Aplastic Anemia (AAA) is a rare hematologic disorder characterized by pancytopenia and hypocelular bone marrow. The pathophysiology is immune mediated in most cases. Environmental exposures to drugs, viruses and toxins, are thought to trigger the aberrant immune response in some patients. However, 50 to 74 percent of cases are classified as idiopathic. The highest frequency occurs in young population (15 to 25 years) with a second peak at age of 65 to 69 years. Immunosuppressive therapy is the best treatment in children with AAA who do not have a suitable donor for allogeneic stem cell transplantation. Materials and methods We reviewed the medical records of patients diagnosed with severe (SAA) and very severe acquired aplastic anemia (vSAA) at the Department of Pediatrics, Instituto da Criança – Hospital das Clínicas, University of Sào Paulo, Brazil from December, 1992 to December, 2007. We analyzed the clinical characteristics of the patients at diagnosis and the response to immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT). Results In this study, 47 patients (27 boys and 20 girls), younger than 16 years, were diagnosed with vSAA (n= 21) or SAA (n=26). The median age was 7,71 years, ranging from 0.5 to 16 years and the average time history (beginning of signs and symptoms related to the disease and diagnosis) of the disease was 4,82 months, ranging from 0,25 to 48 months. Of the 47 patients, 45 had idiopathic AAA and 2 had hepatitis-associated. The median follow-up was 6,91 years for the patients treated with IST and 3,10 years for the patients who underwent to HSCT. One patient died before any treatment. For the eight patients who underwent to allogenic HLA-matched HSCT the 5-years-survival probability was 50%. For the 38 patients treated with IST, ten of them received cyclosporine and a short course of corticosteroids (CsA/CE) and 28 received antithymocyte globulin plus cyclosporine (ATG/CSA). The 5 years survival probability was 40% and 55%, respectively (p:0,0054). According to the severity of AAA, we did not show a significant difference in survival (p:0,32). Eight patients received second treatment after 1 year and 6 months (6 ATG from different species and CsA, 1 CsA and 1 thalidomide) and the probably of survival at 5 years was 60%. Among the 18 patients who responded to IST, four relapsed (22%). Two patients developed acute myeloid leukemia at 5 and 12 years after diagnosis. Conclusion Our results both for patients undergoing HSCT, as well as patients undergoing IST are lower in comparison to other hematological centers. Probably, this discrepancy is related to the prolonged time of disease when patients are admitted to our service. Unfortunately, the difficulty of access to specialized centers for diagnosis and early treatment in our country is a reality and this fact contributes to the delay to the beginning of treatment. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Stem Cell Transplantation Overcomes the Adverse Prognostic Impact of CD20 Expression In Both Adult and Pediatric Acute Lymphoblastic Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1681-1681
Author(s):  
Veronika Bachanova ◽  
Karamjeet Sandhu ◽  
Daniel J. Weisdorf ◽  
Michael Verneris ◽  
Michael J Burke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Disease Recurrence ◽  
Hematopoietic Stem ◽  
Cd20 Expression

Abstract Abstract 1681 The heterogeneous expression of CD20 antigen on leukemic blasts may harbor prognostic value and therapeutic potential. CD20 positivity (CD20+) has been recently associated with disease recurrence and shorter overall survival in adults with pre-B acute lymphoblastic leukemia (ALL). The influence of CD20 expression on outcomes following allogeneic donor hematopoietic stem cell transplantation (HCT) is not known. Results: We analyzed CD20 expression on pre-B ALL marrow blasts at diagnosis in 157 consecutive patients who underwent allogeneic HCT in first or second complete remission (CR) from 1999–2010. Thirty-two patients with no available flow cytometry data were excluded. Out of 125 evaluable patients, 52 (42%) were < 20 years of age; 73 (58%) were ≥20. All patients had high risk ALL and were in CR at HCT (57% in CR1, 43% in CR2). A majority of patients were Ph+ (60%) and received myeloablative conditioning (84%). Grafts were from sibling (36%), unrelated umbilical cord blood (UCB) (59%) and matched adult URD (5%). CD20+, defined as >20% expression on marrow blasts, was observed in 58 (46%) patients. 55% of children and 39% of adults were CD20+ and expression was similar in CR1 & CR2. Gender, donor source (sibling vs UCB), patient CMV serostatus, cytogenetics (Ph+ vs other), and conditioning (myeloablative vs reduced intensity) was similar in CD20+ and CD20- groups. Disease-free survival (DFS) at 3 years was 48% (95% CI 39–57%) for all patients; 42% (95% CI 30–54%) for CD20- patients, and 55% (95% CI 40–67%) for CD20+ patients (p=0.14). CD20+ expression did not significantly impact relapse rate or DFS in adults (Table) while in patients <20 years CD20+ expression was associated with a slightly favorable relapse rate. Similar overall survival (OS) and DFS was seen in both age groups, independent of CD20 expression. Treatment-related mortality was unaffected at 18% (95% CI 9–27%) and 19% (95% CI 9–29%) in CD20+ and CD20- cohorts, respectively (p= 1.00). In adjusted multivariate regression, the CD20+ group had a slightly but not significantly lower risk of relapse (RR 0.54 [0.27-1.09]; p=0.09), yet similar OS (RR 0.66 [0.38-1.14], p=0.13) and DFS (RR 0.67 [0.39-1.14], p=0.14) compared to the CD20- group. Conclusion: Pre-B ALL with a CD20+ immunophenotype reportedly confers higher risk of disease recurrence and unfavorable OS with conventional chemotherapy. Our data demonstrates that the poor prognosis associated with CD20+ ALL blasts is overcome by allogeneic HCT. In addition, post-HCT survival is promising in both adults and children, independent of CD20 expression. CD20 targeting monoclonal antibodies may further improve these outcomes. Disclosures: No relevant conflicts of interest to declare.

The Effect of KIRs Expression Profile in Donor/Recipient Pairs in HLA-Identical Sibling Hematopoietic Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4017-4017
Author(s):  
Xiaoai Wei ◽  
XiaoWen Tang ◽  
Yufeng Feng ◽  
Ziling Zhu ◽  
Jun He ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Expression Profile ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
Matched Group

Abstract Abstract 4017 Objective: We investigated the distribution characteristics of KIRs expression profile in donor/recipient pairs with acute leukemia (AL) receiving HLA-identical sibling hematopoietic stem cell transplantation (sib-HSCT). We further explored the effect of KIRs expression profile in donor/recipient pairs on clinical outcome, including dynamics of donor T cell and NK cell engraftment. Methods: The genotypes of donor/recipient KIRs were determinated by polymerase chain reaction- sequence specific primer (PCR-SSP) for 80 pairs of donor/recipient receiving HLA-identical sibling hematopoietic stem cell transplantation. The multiple short tandem repeat (STR) PCR was used to evaluate the status of engraftment of donor T cells and NK cells at +14 days, 21 days, 28 days, 60 days and 90 days after transplantation in 24 cases. Results: 1. In 80 pairs of donor/recipient: (i) the KIRs were completely identical in 57.5% of donor/recipient pairs; (ii) the donors' KIRs contained the recipients' in 13.75% pairs; (iii) the recipients' KIRs contained the donors' in 17.5% of pairs; (iv) the KIRs were completely different in 11.25% pairs. The graft versus host (GVH) direction KIR-matched group was 75%. The percentage of group donor B/X and group donor A/A was 50%, respectively. 2. Comparing the patients from GVH direction KIR-matched and mismatched group, the incidence of acute (a) GVHD was 60% and 30%, respectively (P =0.0222), and 2-year OS was 62.96% and 94.12%, respectively (P =0.0492). Particularly, grade III-IV aGVHD rate of KIR-matched group was higher than that of non-KIR matched group(15% vs 0%). 3. Donor B/X group had a higher 2-year OS and 2-year relapse-free survival (RFS) compared with donor A/A group (89.23% vs 49.57%, P =0.0159, and 90% vs 59.71%, P =0.0239, respectively). Patients with three or less aKIRs had a lower 2-year OS (58.9% vs 92.44%, P =0.0338) and a lower RFS (65.14% vs 92.59%, P =0.0398), compared with patients with more aKIR. 4. Sequential monitoring of chimerism status of donor NK-cells in 24 cases revealed that on day+14, the percentage of full donor NK cells chimerism was higher in non-KIR matched patients than that of KIR matched patients (85.7% vs 52.9%, P =0.0456). Conclusions: Donor KIR genotype appears to have a direct impact on aGVHD, OS and RFS. Therefore, donor KIR genotype should be evaluated as an outcome predictor of the HLA-identical sib-HSCT. Disclosures: No relevant conflicts of interest to declare.

Combination of Mitoxantrone,Ara-C and Homoharringtonine In Treatment of Refractory and Relapsed Acute Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4294-4294
Author(s):  
Jianda Hu ◽  
Tingbo Liu ◽  
Chunxia Cai ◽  
Xinji Chen ◽  
Buyuan Chen
Keyword(s):  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract Abstract 4294 Advances in effective chemotherapy have improved clinical outcomes in acute leukemia in recent years. 5-year survival rate approaches 50–60% for acute myeloid leukemia (AML). However, the prognosis remains poor for patients who are relapsed or refractory to first-line therapy. Drug resistance and early disease recurrence are major contributing factors in the limited survival of patients with AML. The strategy for treating these patients is through reinduction chemotherapy followed by allogeneic stem cell transplantation. New combinations of different agents were employed in refractory patients to overcome drug resistance. The current study is to evaluate the efficacy of a MAH regimen comprising Mitoxantrone,Ara-C and Homoharringtonine in refractory or relapsed AML. 37 patients aged 14–65 years with refractory or relapsed AML (15 refractory AML patients, 22 relapsed AML patients) were treated with the MAH regimen(Mitoxantrone 10mg qd, iv.gtt, for 2□‘3 days;Ara-C 100mg bid, iv.gtt, for 5□‘7 days; Homoharringtonine 4mg qd iv.gtt, for 5□‘7 days). Chemotherapy duration lasted for 5 or 7days depended on bone marrow cellurarity. 15 (40.5%)and 1 (2.7%) patients achieved complete remission (CR) and partial remission (PR) respectively. The overall response rate was 43.2%. There was no relation between remission duration and previous chemotherapy. All patients who achieved CR received a consolidation and intensification therapy. The median overall survival (OS) for all patients was 97 days (range 18–487 d). For the patients who were in CR or PR,the median relapse-free survival(RFS) was 147 days(range 4 to 341 d). All patients experienced profound myelosuppression. The most common observed side effect of the regimen was infection because of grade ‡W neutropenia, which could be observed in 33 patients(89.1%). 4 patients died in aplasia due to severe infection and brain hemorrhage. In patients achieving remission, the median time to reach absolute neutrophil count (ANC) more than 0.5×109/l was (16.0±6.4)d. Platelet levels of more than 20×109/l were achieved in a median time of (12.7±6.2)d. Nonhematological side effects, consisting mainly of gastrointestinal toxicity(21/37,56.8%) and transient liver ALT and AST increase (4/37), were generally mild to moderate and tolerated. To a conclusion, MAH regimen can be employed in treatment of the refractory or relapsed AML patients who were not responded to other regimen. It is effective and is good tolerant.It could provide some refractory patients the chance to receive hematopoietic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Haploidentical Mismatched Allogeneic Versus Autologous Hematopoietic STEM CELL Transplantation in Adult Patients with ACUTE Myeloid Leukemia (AML) in First Complete Remission (CR1): A Pair-Matched Analysis From the Acute Leukemia Working Party of EBMT.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3093-3093
Author(s):  
Norbert C. Gorin ◽  
Myriam Labopin ◽  
Fabio Ciceri ◽  
Andrea Velardi ◽  
Stella Santarone ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Adult Patients ◽  
Matched Pair ◽  
Hematopoietic Stem ◽  
First Choice ◽  
Alternative Donor ◽  
Family Donor

Abstract Abstract 3093 In the absence of a matched family donor, adult patients with AML in CR1 are nowadays usually offered, as a first choice, an allogeneic transplant from an alternative donor (haplomismatched donor or cord blood cells), but there has been thus far no demonstration that outcome when using an alternative donor would be superior to outcome following an autologous stem cell transplantation (ASCT). Between January 2000 and December 2010, 113 AML patients transplanted in CR1 with an haplo-mismatched family donor and 4444 patients autografted were reported to the EBMT registry. For the purpose of this analysis, we performed a matched pair analysis (113 haplo/226 autos) using age and interval from diagnosis to transplant as matching factors. The median follow up was 18 months (range, 1–128). Patients allografted were transplanted more recently (median year of transplant: 2008 vs 2004, p<10e-4), and they received more frequently total body irradiation in the pretransplant regimen (58% vs 17%). Engraftment following an haplo- mismatched transplant occurred in 93% of cases vs 99% after ASCT and recovery of ANC>500/mm3 was slightly delayed (15 days vs 13 days, p<10e-4). The outcome at two years, following an haplo mismatched transplant versus an ASCT was: LFS 44±5% vs 54±4% (p=0.008); OS 44±6 % vs 68±4% (p<10e-4); Non Relapse Mortality (NRM) 37±5% vs 2±2 ( p<10e-4) and Relapse Incidence (RI) 19±4% vs 43±4% (p<10e-4). Following an haplo mismatched transplantation the incidence of chronic extensive GVHD was 24+/− 6%. By multivariate analysis adjusted on year of transplantation, source of stem cells and TBI, the RI was no longer statistically different between the 2 groups, NRM was higher following haplo (HR=11.8; p<0.0001) and LFS was better following ASCT (HR=0.52; p=0.004). Though this study did not account for cytogenetics and molecular markers (data collection is ongoing), these results suggest that outcome following ASCT in CR1 may be better compared to outcome following a haplo-mismatched transplantation. Recent developments in both transplant approaches may change the results in the near future and may justify a randomized prospective study. Disclosures: No relevant conflicts of interest to declare.

Femoral Head Necrosis In Three Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5489-5489
Author(s):  
Gang Zhao ◽  
Zhi Li ◽  
Jiahua Ding ◽  
Jun Wang ◽  
Zhengping Yu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Femoral Head ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Femoral Head Necrosis ◽  
Hematopoietic Stem

Abstract Femoral head necrosis (FHN) is one of common complications after hematopoietic stem cell transplantation (HSCT). It impacts on patients' normal life with severe pain. To investigate FHN after allogeneic HSCT, We performed retrospective analyses. Since 2003, our department has conducted 98 cases of allogeneic hematopoietic stem cell transplantation for patients with hematologic diseases. Chemotherapy regimens and transplant conditioning regimen before transplantation were steroid-free. FHN occurred in 3 out of 98 cases. The 3 patients were treated with steroid for preventing graft versus host disease (GVHD) after transplantation. However, all the three patients suffered from GVHD, which was cured with steroidal medication subsequently. Then, symptoms of FHN come out and were significantly improved after conservative treatment in all the three patients. The occurrence of FHN might be associated with GVHD and corticosteroids prescription. Early prevention might be helpful in reducing the incidence and improving outcomes. Disclosures: No relevant conflicts of interest to declare.

Evaluation of Blood Group Conversion Following ABO-Incompatible Hematopoietic Stem Cell Transplantation (HCT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1557-1557 ◽  
Author(s):  
Esther HL Chan ◽  
Thiow Christofer ◽  
Susan TT Lim ◽  
Lip Kun Tan ◽  
Michelle Poon
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Blood Group ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
Body Tissues ◽  
Group Data

Abstract Title: Evaluation of blood group conversion following ABO-incompatible Hematopoietic Stem Cell Transplantation (HCT). Background: While there have been a number of reports concerning the influence of AB0 incompatibility on hematopoietic transplantation (HCT) outcomes, data evaluating post-HCT blood group conversions following ABO incompatible transplants remains extremely limited. Methods: We performed a single centre retrospective analysis of 97 patients undergoing major or minor or bidirectional ABO-mismatched bone marrow (BM), peripheral blood (PB), and cord blood (CB) hematopoietic stem cell transplantation (HCT) between January2005 – April 2014, in whom engraftment had occurred and blood group data was available. The aim of the study was to analyse the red cell ABO phenotype (forward grouping) and levels of anti-A/B antibodies (reverse grouping) in these patients following the ABO-mismatched transplants. Results: 97 patients transplanted between January 2004 and April 2014 were included in the analysis. There were 40 (41%) matched sibling, 32 (33%) matched unrelated and 25 (26%) CB transplants. Indications for HSCT included both haematological malignancies (n=87) and benign conditions (n=10). Of these donor recipient pairs, there were 44 (45%) minor, 39 (40%) major and 14 (15%) bidirectional ABO mismatches. All patients had achieved full donor type chimerism at the time of analysis. Analysis of post –HCT blood group conversion was performed in each of the three groups. Amongst the major mismatch patients (n=39), all had conversion of RBC phenotype to donor ABO phenotype and loss of their host derived anti-donor ABO antibodies. Interestingly, in the minor mismatch patients who were tested (n=44), all the patients had conversion of their RBC phenotype, but 43 out of 44 patients failed to produce recipient directed anti-ABO antibodies. Similarly in the bidirectional mismatch group, all 14 patients converted to donor ABO phenotype, but none produced recipient directed anti-ABO antibodies. Conclusion: In one of the largest study looking at this issue, our study demonstrated the lack of a development of recipient directed anti A/B antibodies despite complete donor chimerism in the majority (1 out of 58) of patients undergoing minor or bidirectional ABO-mismatched HSCT. We postulate that this phenomenon may be due to the donor B cell tolerance against host ABO antigen due to the presence of host A and B antigens within other body tissues. Disclosures No relevant conflicts of interest to declare.

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