Successful Result of 113 Patients for Refractory/Recurrent Leukemia By Allogeneic Hematopoietic Cell Transplantation and Prophylactic Immunotherapy

Abstract Objective: To retrospectively evaluate the results of allogeneic hematopoietic stem cell transplantation for Refractory/Recurrent leukemia. Methods: From July 2012 to May 2016, total 113 patients with Refractory/Recurrent leukemia were enrolled, including 31 cases of ALL, 73 cases of AML and 8 cases of CML-BP, 1 case of Prolymphocytic leukemia. The average leukemia burden was 51% (10-99) in bone marrow before conditioning. Myeloablative conditioning regimens consisted of 13 cases of BuCy, 47 cases of TBI/FLAG, 28 cases of TBI/Cy, and 16 cases of FLAG that followed by reduced-intensified BUCY, 9 cases of CLAG/BuCy. Transplant types included sibling HLA-identical allo-HSCT (n=22) and relative HLA-haploidentical HSCT (n=91). All patients received cyclosporine A, MMF and methotrexate for GVHD prophylaxis. Analyzed outcomes were hematological engraftment, incidence of acute and chronic GVHD, incidence of CMV/EBV infecton, incidence of relapse, and nonrelapse mortality (NRM), Overall survival (OS) and Disease-free survival (DFS). Results: The median mononuclear cells and CD34+ for transfusion were 8.83 (7.02-11.64) ×108/Kg and 2.91 (0.8-8.32) ×106/Kg. 111 patients achieved stable engraftment, 2 patients died of infection before engraftment. The median time of ANC≥0.5×109/L was 16 days(8-29) and the median time of platelet ≥20×109/L was 22 days (8-150). On day 28postallogeneic transplant, 110 patients were in complete remission of bone marrow, 1 patient was in hematologic relapse. Immunity residue were negative in 107 patients and positive in 4 patients. 62 patients developed acute GVHD, the accumulative incidence of aGVHD was (57.6±4.8)%, the accumulative incidence of II-IV grade aGVHD was (47.2±4.8)%, and the accumulative incidence of III-IV grade aGVHD was (25.2±4.1)%. 62 patients developed cGVHD (43 patients extensive, 19 patients limited), the accumulative incidence of cGVHD was (70.2±6.6)% and for extensive type, the accumulative incidence was (43.6±5.2)%. The accumulative incidence of CMV infection was (42.3±4.7)%, and the accumulative incidence of EBV infection was (4.5±2)%. 10 patients developed virus cystitis, and the accumulative incidence was (9.1±2.1)%. The median follow-up time post transplantation was 10 months (1-46), 35 patients occurred hematologic relapsed and the accumulative incidence of relapse was (39.7±5.9)%. For AML, ALL and CML-BP patients, the accumulative incidence of relapse were (33.8±6.9)%, (56.6±11.7)% and (25±15.3)%respectively (p>0.05). On median follow up (10 months), 49 patients died and 64 patients survived. The cause of death included relapse (28 cases), infection (6 cases), GVHD (11 cases) diffuse alveolar hemorrhage (2cases), radiation enteritis (1 case), and TMA (1 case).Among 64 survirors, two-year accumulative incidences of OS were (49.3±5.7)%, and two-year accumulative incidences of LFS were (45.1±5.4). The two-year accumulative incidences of OS for AML, ALL and CML-BP patients were ( 52.4±7.1)%, (28.1±9.7)%,and (87.5±11.7)%respectively (p>0.05). The two-year accumulative incidence of LFS for AML, ALL and CML-BP patients were (49.8±6.5)%, (24.7±9.1)%, and (70±18.2)%respectively (p>0.05). Incidence of relapse, OS and LFS were similar in different conditioning cohorts (p>0.05). There was no significant difference in the incidence of relapse, OS and LFS over two years among patients with C-Kit, FLT3, MLL and without such genes(p>0.05). There is significant difference in incidence of relapse, OS and LFS among patients with different leukemia burdens(p<0.01). Patients with leukemia burden at 10-19% has lower relapse rate but higher OS and LFS compared to patients with leukemia burden at 80%. Incidence of relapse, OS and LFS for the prophylactic immunotherapy cohort were 32.9%, 61.1% and 57.6% respectively, compared to 45.2%, 35.8% and 35% for non prophylactic immunotherapy cohort (p<0.01). Incidence of relapse , OS and LFS for the cGVHD cohort were 12.9%, 68.4% and 66.2% respectively, compared to 78.7%, 13.9% and 12.8% for non cGVHD(p<0.01). Incidence of relapse , OS and LFS for extensive cGVHD cohort were 12.3%, 62.1% and 61.8% respectively, compared to 58.8%, 31.4% and 31.2% for non extensive cGVHD(p<0.01) Conclusion: Our clinical results have shown that the salvaged HSCT is a promising modality for treatment of Refractory/Recurrent leukemia. Especially for Refractory/Recurrent AML and CML-BP. Disclosures No relevant conflicts of interest to declare.

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Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic Syndrome: Impact of Age and Conditioning

Blood ◽

10.1182/blood.v124.21.5939.5939 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5939-5939

Author(s):

Jörg Schmohl ◽

Spanier Lena ◽

Christiane Dorn ◽

Christoph Faul ◽

Wichard Vogel ◽

...

Keyword(s):

Cell Transplantation ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Progression Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Allogeneic Hct ◽

Significant Difference ◽

Group A ◽

Group B

Abstract Introduction: Myelodysplastic syndromes (MDS) are one of the main indications for allogeneic hematopoetic cell transplantation (HCT). With the introduction of reduced intensity conditioning regimens (RIC) this curative therapy is increasingly used in elderly (≥60 years) or comorbid patients (pts). Methods: Here we retrospectively analyzed data obtained in 81 consecutive adult MDS patients (f=32, m=49) that underwent allogeneic HCT using either myeloablative (MAC) regimens (Busulfan (Bu)/Cyclophosphamid (Cy) (n=13), Cy (n=1); Cy/Total Body Irradiation (TBI) 12Gray (n=6)) or RIC (FLAMSA/Fludarabin (Flu)/Bu (n=3); Flu/Bu (n=28); Flu/TBI (n=5); Flu/Thiotepa/Melphalan (Mel) (n=2); Flu/Treosulfan (n=12), FLAMSA/Bu/Cy (n=1), Flu/Cy/TBI (n=2), Flu/Mel (n=2)). For graft versus host disease (GVHD) prophylaxis, calcineurin inhibitor combined with mycophenolate mofetil (n=24) or methotrexate (n=41) and anti-thymocyte globulin (n=60) were used. Results: Median age at first diagnosis of patients was 53 years (range 21-72). Pts were grouped in 2 age categories: pts <60 years (group A, n=57) and >60 years (group B, n=24). Pts suffered from MDS/CMML 5q, n=2; CMML I, n=3; CMML II, n=2; RAEB I, n=21; RAEB II, n=21; RCMD, n=27; RCUD, n=2. Median IPSS score in group A and B was 1.4. 32% of group A and 35% of group B had an IPSS Score below 2. Mean HTC-CI in group A was 1.4, in group B 1.7. Grafts either from matched related (A, n=18, B, n=2), matched unrelated (MUD; A, n=25, B, n=13) or mismatched unrelated (MMUD; A, n=7, B, n=9) donors were used. Conditioning in group A was MAC (n=20) or RIC (n=31) whereas all patients in B received RIC. No significant age-associated influence was observed with regard to median survival (A, 44 months; B, 26 months; p=0.7) or estimated 3 year overall survival (OS) (A, 33%; B, 19%; p=0.3). Median observation time of patient alive was 40 months (range 3-168 month). Cumulative incidences of non-relapse mortality adjusted for relapse as competing risk showed no significant difference for group A and B. Progression free survival was not significantly different between the groups (A, 20 months; B 12 months; p=0.25). Kaplan-Mayer Analysis showed no difference in OS between risk groups; however, progression free survival was significantly lower in the group with IPSS >2 (7 vs 22 months, p=0.02). Within 100 days, neither in A nor B non-relapse mortality (NRM) was documented. The use of a MMUD appeared to have a negative but not significant influence in older pts on OS (3-year OS in A: MUD 75% vs. MMUD 25%, p=1.00; B: MUD 100% vs MMUD 0%, p=0.2). Incidence of GvHD ≥II was in 14% vs. 6% in A and B. Incidence of chronic GVHD was 42% in A (limited=12, extensive=12) and 37% in B (limited=4, extensive=5). Conclusion: RIC represents a promising treatment option in elderly MDS pts and allows for allogeneic HCT even in comorbid pts. Age had no negative impact on survival. Interestingly, IPSS score has an influence on progression free survival in patients. Disclosures No relevant conflicts of interest to declare.

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Allogeneic Stem Cell Transplantation (Allo-SCT) Following a Reduced-Intensity Conditioning (RIC) Regimen in Relapsed Peripheral T-Cell Lymphomas (PTCL): Results at 4 Year of Median Follow-up.

Blood ◽

10.1182/blood.v114.22.875.875 ◽

2009 ◽

Vol 114 (22) ◽

pp. 875-875

Author(s):

Anna Dodero ◽

Francesco Spina ◽

Franco Narni ◽

Francesca Patriarca ◽

Sergio Cortelazzo ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Disease Progression ◽

Cell Transplantation ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Multivariable Analysis ◽

Number Of Patients ◽

Significant Difference

Abstract Abstract 875 Conventional therapies and autologous stem cell transplantation lead to disappointing results in relapsed PTCL, therefore allo-SCT has been investigated in the last years. There are evidence supporting the existence of a “graft-versus-PTCL” effect, but the majority of the studies have a limited number of patients with a short follow-up. We conducted a retrospective analysis on 53 patients (pts) affected by relapsed/refractory PTCL who received a RIC regimen followed by allo-SCT. The main histopathological subtypes were PTCL-not otherwise specified (PTCL-NOS, n=24), anaplastic large-cell lymphoma (ALCL, n=11), and angioimmunoblastic (AILD, n=6). The remaining cases were rare subtypes (n=12). Median age was 47 years (range, 15-64 years). Patients were allografted from matched related siblings (n=34, 64%) or alternative donors (n=19, 36%). The majority of pts had chemosensitive disease (n=39, 74%), received allo-SCT more than 12 months from diagnosis (n=38, 72%) and were treated with only 1 or 2 lines of therapy before transplantation (n= 37, 70%). At last follow-up (median 49 months, range 6-118), 29 pts are alive (55%, 26 in CR) and 24 died [n=20 for disease progression, n=4 for non-relapse mortality (NRM)]. The majority of relapsing patients (20 of 25, 80%) died at median time of 7 months after allo-SCT. The crude cumulative incidence (CCI) of relapse was 32% and 50% at 6 months and at 4-year after allo-SCT. The CCI of relapse was influenced by status of disease [chemosensitive versus chemorefractory: 41% versus 77% at 4 years (p<0.001)] and number of lines [≤ 2 versus > 2: 40% versus 70% at 4 years (p<0.02)] received before allo-SCT and not by hystotype and time from diagnosis to allograft. The CCI of NRM were 4% and 10% at 6 months and 4-year, respectively; type of donor and previous auto had no significant impact on NRM. The CCI of acute (grade II-IV) and chronic GVHD were 21% and 44%, respectively. The 4-year OS and PFS were 50% (95% CI, 35% to 63%) and 47% (95% CI, 32% to 60%) for all the population, 62% (95% CI, 44% to 76%) and 15% (95% CI, 3% to 38%) as OS, 58% (95% CI, 40% to 72%) and 13% (95% CI, 1% to 41%)as PFS, for chemosensitive and chemorefractory pts, respectively. According to the histopathological subtypes, the OS and PFS were 42% and 40% for PTCL-NOS, 50% and 44% for ALCL, 67% and 80% for AILD, 58% and 48% for rare subtypes, respectively (p=ns). At multivariable analysis of OS and PFS, refractory disease prior to alloSCT and age more than 45 years were independent adverse prognostic factors [hazard ratio (HR)= 5.3, p<0.001, HR=4.8, p<0.003 for OS; HR=5.4, p<0.0007, HR=2.7, p<0.02 for PFS]. Six-teen pts received donor lymphocytes infusions (DLIs) for disease progression (n=12) or to accelerate immune reconstitution (n=4): 7 out of 12 responded to DLIs (n=3 CR, n=4 PR). In conclusion, our long-term data with a median 4-year follow-up shows that: i) only patients with chemosensitive had advantage from allo-SCT; ii) transplantation should be performed early because pts receiving less lines of therapy had a better outcome; iii) we did not observe a significant difference in outcome between the different histopathological subtypes; iv) response to DLI supports the notion of an immune mediated effect. Disclosures: No relevant conflicts of interest to declare.

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HLA-Haploidentical Hematopoietic Stem Cell Transplantation In An Infant with Malignant Infantile Osteopetorosis.

Blood ◽

10.1182/blood.v116.21.4585.4585 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4585-4585

Author(s):

Taichi Omachi ◽

Hirohide Kawasaki ◽

Yukihiro Noda ◽

Kazunari Kaneko

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Hematopoietic Stem ◽

Bone Marrow Scintigraphy

Abstract Abstract 4585 Malignant infantile osteopetrosis is an autosomal recessive disease characterized by a lack of osteoclastic function with incidence of 1: 200,000 to 1: 300,000. In consequence of disturbed bone building and remodeling, affected patients have osteosclerosis, dense fragile bone, and a marked reduction in the bone marrow cavity. Clinical features, such as anemia, thrombocytopenia, hepatosplenomegaly, bone fractures, bone deformity, and cranial nerve entrapment, appear soon after birth or within the first years of life. In the natural course of the disease, only 30% of children can survive to more than six years old. Because osteoclasts are of hematopoietic origin, allogeneic stem cell transplantation is the only curable therapy. Recently, successful HLA-haploidentical hematopoietic stem cell transplantation (HSCT) has been reported for patients without HLA- matched donors. We also present an infant with malignant infantile osteopetrosis who underwent HLA-haploidentical HSCT. A four-month-old boy was referred to our hospital for splenomegaly and pancytopenia. A physical examination revealed failure to thrive, distention of anterior fontanel, and hepatosplenomegaly. Laboratory findings indicated thrombocytopenia and anemia, and elevated alkaline phosphatase. Osteoclasts were hyperplastic in bone marrow. Radiography showed homogeneous and sclerotic bones with absence of corticomedullary junction, and bone marrow scintigraphy showed no accumulation of bone marrow. Subsequently, TCIRG1 mutations are identified. All these findings are compatible with malignant infantile osteopetrosis and the diagnosis was made. We conducted HSCT to revive his osteoclastic function. However, he didn't have HLA-matched donors not only in relatives but also in the bone marrow bank and the cord blood bank of Japan. We attempted HLA-haploidentical bone marrow transplantation (BMT) from his father with written informed consent. The patient was prepared for BMT at 11 months of age by conditioning with busulfan (6 mg/kg × 4/day × 4 days), cyclophosphamide (360mg/m2 × 2 days) and antithymocyte globulin (2 mg/kg/day × 3 days). Prophylaxis for graft-versus-host disease (GVHD) included tacrolimus and short-term methotrexate. Bone marrow nuclear cells (1×109/kg) were collected from his father and transplanted without any manipulations. The engraftment of neutrophils was confirmed on day 9 after BMT. Acute GVHD was limited to the skin (grade I). At 2 months after BMT, neutrophil counts, platelet counts, and hemoglobin level were all within normal limits. Bone marrow scintigraphy revealed a significant uptake in bone marrow. There have been no chronic GVHD up to six months after BMT.HSCT for patients with osteopetrosis is challenging as it is reported that HLA-haploidentical HSCT has the high rate of acute and chronic GVHD. Fortunately, HLA-haploidentical BMT was successful in our patient. This might be due to our regimen for prophylaxis of rejection and GVHD. We used ATG in conjunction with tacrolimus: this regimen may be prophylactic not only for rejection but also for GVHD as previously reported (Schulz et al. Blood 2002; 99: 3458–3460). In conclusion, HLA-haploidentical family donors should be considered as the alternative hematopoietic stem cell source for patients with malignant infantile osteopetrosis in condition without HLA-matched donors. Disclosures: No relevant conflicts of interest to declare.

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Bone Marrow (BM) Versus Peripheral Blood Stem Cell (PBSC) For Haploidentical Transplantation With Nonmyeloblative (NMA) Conditioning Regimen and Post Infusion Cyclophosphamide

Blood ◽

10.1182/blood.v122.21.2119.2119 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2119-2119

Author(s):

Luca Castagna ◽

Roberto Crocchiolo ◽

Sabine Furst ◽

Stefania Bramanti ◽

Barbara Sarina ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Median Time ◽

Hematological Malignancies ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Haploidentical Transplantation ◽

Post Infusion

Abstract Introduction Transplantation from alternative donors has been used since several years for patients with hematological malignancies lacking of HLA identical donors. The Baltimora group pioneered the use of cyclophosphamide (Cy) after haploidentical unmanipulated (BM) stem cells infusion. BM was chosen to reduce the risk of acute and chronic graft versus host disease (GVHD). PBSC could replace BM, fastening engraftment and immunological reconstitution. However, the risk of GVHD could be higher. We retrospectively analyzed a cohort of patients from two institutions, receiving haploidentical transplantation with nonmyeloablative conditioning regimen (NMA) and PSBC or BM, with post-infusion Cy. Patients and Methods From April 2009 to April 2013, 72 patients with poor prognosis hematological malignancies received haploidentical transplantation. Conditioning regimens consisted of Cy 14.5 mg/kg d -5 and -6, fludarabine 30 mg/m2 d-6 to d-2, and low dose TBI (2 Gy) at d-1. GVHD prophylaxis consisted of Cy 50 mg/kg day +3 and +4, tacrolimus (FK, 1 mg total dose, in continuous infusion) until days +180 (Milan cohort) or cyclosporine (CsA, 3 mg/kg) (Marseille cohort) and MMF (15 mg/kg 3 per day) until day +35. FK, CsA and MMF were started at d +5. G-CSF was started at d +5 in all patients. Donors underwent bone marrow harvest under general anesthesia and a total of 4 x 10e8 nuclear cells per kg of recipient was targeted. Unmanipulated bone marrow was used as stem cell support at d0. In Marseille, donors were mobilized using 5 to 6 days of subcutaneous G-CSF (Neupogen®) (10 mcg/kg/day). A minimum of 4 x 10e6 CD34/kg was harvested. Results The median follow-up was 12 months (range: 1-48). For the population as a whole, the median time to ANC more than 0.5 x 10e9/L was 20 days (14-32) and the median time to transfusion-independent platelet (PLT) count was 29 days (14-52). Engraftment results in the two cohorts of patients (BM vs PBSC) were not significantly different [ANC 21 days (14-32) vs 20 days (14-27), and PLT 29 days (16-46) vs 27 days (14-52)]. Overall, aGVHD 2-4 incidence was 27% and cGVHD was 13%. No difference was founded in the two cohorts: aGVHD 2-4 24% vs 33% and cGVHD 11% vs 17%. The 1-year non relapse mortality was 18% overall, and it was not statistically different even if numerically lower in the PBSC group (22% vs 9%). Conclusion This retrospective study showed that there was not significant differences in terms of hematological reconstitution and both acute and chronic GVHD, using unmanipulated BM and PBSC after NMA conditioning regimen and post-infusion Cy. The 1-year NRM, even if not statistically different, was lower with PBSC. These data warrant confirmation with more patients and longer follow-up. Disclosures: No relevant conflicts of interest to declare.

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Is Not Age, But Comorbidities. Allogeneic Hematopoietic Stem Cell Transplantation In Patients Older Than 50 Years In Argentina

Blood ◽

10.1182/blood.v122.21.5467.5467 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5467-5467

Author(s):

Mariano Berro ◽

Juan Garcia ◽

Ana Basquiera ◽

Maria Marta Rivas ◽

Maria Cecilia Foncuberta ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Disease Free Survival ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Transplant Outcome ◽

Significant Difference

Abstract Materials and Methods We retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplant (HSCT) in 9 centers from Argentina. We evaluated the following characteristics: sex, age, diagnosis, stage, comorbidities (according to the HCT-CI score), type of donor, histocompatibility, source, conditioning and immunosupression. We analyzed the incidence and severity of acute Graft-vs-Host disease (aGVHD) with Chi Square, Overall Survival (OS) and Disease Free Survival (DFS) with Kaplan Meier and Relapse, Non Relapse Mortality y chronic GVHD (cGVHD) with CI. For multivariate analysis (MA) we included variables that in univariate had a p<0.2, used Cox regression model for time dependant outcomes and logistic regression for dichotomic variables, considering significant a p<0.05. Results Patients characteristics are listed in table 1. Between January 1997 and July 2013, 137 transplants were performed in adults older than 50 years, with a median follow up 1.3 years. Acute GVHD incidence was 41% (19% were grade II and 7.3% III-IV). The only variable associated with aGVH clinically significant (G II-IV) was AML that was protective (14% vs 35%, p<0.01; significant in MA, HR 0.29; 95% CI 0.12-0.72). Chronic GVHD incidence was 25%, extensive in 9.4% and the only risk factor for this outcome was MPN (1-3 years 40%-NA vs 12-20%, p=<0.01). Global OS 1 and 3 years was 44 and 20%, DFS was 33 and 20%, Relapse was 35 and 41% and NRM was 36 and 43% respectively. Co-morbid patients showed a significant increase in NRM (HCT.CI 0 vs 1 vs ≥2, 1-3 years 17-24%, 40-46% and 45-67%, p=0.01; significant in MA, for HCT.CI 0 vs ≥1, HR 2.4, 95% CI 1.12-5.25), as well as male patients (1-3 years 36-47% vs 23-27%, p=0.03), MPN (1-3 years 43-65% vs 29.34%, p=0.01) and Cyclosporine based immunosuppressant regimen (CSA) vs tacrolimus (1-3 years 47-53% vs 25-36%, p=0.01). AML patients experienced a higher relapse rate (1-3 years 50-50% vs 28-32%, p<0.01) as well as Fludarabine-Busulfan conditioning (1-3 years 45-48% vs 31-32%, p=0.02). Finally patients without comorbidities (HCT.CI 0 vs ≥1) had higher OS (1-3 years 54-30% vs 36-16%, p=0.03) and DFS (1-3 years 43-31% vs 30-15%, p=0.05) as well as tacrolimus vs CSA base regimen that had higher OS (1-3 years 49-25% vs 31-13%, p=0.01) and DFS (1-3 year 41-26% vs 20-11%, p<0.01; significant in MA, HR 0.56, 95% CI 0.33-0.98). Age (older than 60 vs younger), type of donor, use of myeloablative conditioning regimen and source did not showed any significant difference in the outcome analyzed. Conclusion HSCT is a valid therapeutic option for older patients. In this retrospective analysis of patients older than 50 years, we found that the main risk factors that impact in transplant outcome are patients comorbidities and not age, whereas transplant related toxicities increase with the number of comorbidities and therefore decrease OS and DFS. Beyond the fact that certain disease experienced more aGHVD (AML) or cGVHD and higher NRL (MPN) the other factor significantly related in transplant outcome was the use of tacrolimus vs CSA. Disclosures: No relevant conflicts of interest to declare.

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Comparison of the DONOR Lymphocyte Infusion and Second Allogeneic STEM-CELL Transplantation in the Treatment of First Hematological Relapse after Allogeneic STEM-CELL Transplantation in Adults with ACUTE Leukemia

Blood ◽

10.1182/blood-2019-121599 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5698-5698

Author(s):

Haluk Demiroglu ◽

Elifcan Aladag ◽

Nelson J. Chao ◽

Yahya Buyukasik ◽

Hakan Goker

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Acute Leukemia ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Donor Lymphocyte Infusion ◽

Hematopoietic Stem ◽

Significant Difference

Purpose: Relapse after allogeneic hematopoietic bone marrow transplantation (AHSCT) in acute leukemia is a poor prognosis indicator. Although there is no definite opinion about the optimal treatment chemotherapy, second allogeneic hematopoietic stem cell transplantation (AHSCT2) or donor lymphocyte infusion (DLI) are among the treatment options. Relapse after allogeneic transplantation remains unfortunately quite common and we frequently face difficult management decisions. The decision to offer either option is based on several factors, including donor availability, remission status, presence of disabling comorbidities, and center or physician preference. The aim of this study was to investigate the effect of AHBMT2 or DLI on survival in relapsed transplant patients suffers from acute leukemia. Method:We here in report a retrospective analysis of single-center experience with AHBMT2 and DLI to treat patients relapsing from acute leukemia after a first AHBMT from 2003 to 2018.We enrolled the study 20 patients who underwent DLI and 6 patients who underwent AHBMT2. Result:There was no significant difference in OS between the groups afterward intervention (p:0,9) The 2-year survival rate was 33% in the AHBMT2 group and 43% in the DLI group. After intervention, chronic GVHD was observed only in DLI group. Conclusion: DLI can be considered after relapse as a safer and less toxic method than AHBMT2. Disclosures No relevant conflicts of interest to declare.

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Should We Hold the Point of allogeneic Hematopoietic Stem Cell Transplantation for Paroxysmal Nocturnal Haemoglobinuria in Eculizumab Era?

Blood ◽

10.1182/blood.v124.21.5165.5165 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5165-5165

Author(s):

Feng Chen ◽

Wu Depei ◽

Aining Sun ◽

XiaoWen Tang ◽

Chengcheng Fu ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Cumulative Incidence ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Hematopoietic Stem

Abstract PNH is a rare haematological disorder due to the clonal expansion of abnormal haemotopoietic stem cells ,carrying a mutation in the PIG-A gene. Eculizumab ,as a humanised anti-complement component (C5), has proven highly effective in controlling intravascular haemolysis, and is expected to result in a remarkable improvement of survival. Should Eculizumab thus be offered as first treatment to all PNH patients? Allogeneic hematopoietic stem cell transplantation is still the only curative treatment for PNH by eradicating the abnormal PNH clone, leading to definitive survival improvement and QOL benefits. Methods We assessed the long-term clinical and hematologic results in 13 PNH patients who received Allogeneic hematopoietic stem cell transplantation in our centre between Jan 2010 and Apr 2014. The patients were aged 13 to 54 (median 24 years). Eight donors were HLA -haploidentical and 5 were HLA-identical (3 siblings and 2 unrelated donors). Results Eleven patients received a myeloablative conditioning consisting of busulfan and cyclophosphamide and 2 were given a reduced intensity conditioning consisting of fludarabine, busulfan and ALG (2 HLA-identical sibling donor). All patients achieved sustained engraftment with a median time of 11 days (range 11-26) to reach 0.5 ×109/L neutrophils and 15 days (range 12-126) to reach 20 ×109/L platelets. The overall cumulative incidence of grade II-IV acute GvHD was 15.4% and 2 patients showed limited chronic GvHD in evaluable 12 patients (cumulative incidence 16.7%).Transplant-related mortality for all patients was 15.4% (1 due to TMA and 1 due to severe pulmonary infection). As of Aug 1,2014, 11 patients are alive with complete hematologic recovery and no evidence of PNH following a median follow-up of 13 months. The 3-year Kaplan-Meier probability of disease-free survival was 80.2±12.8%. No thromboembolic event nor recurrence of the disease were reported following transplant. Conclusions The findings of this study confirm that most patients with PNH may be definitively cured with allogeneic hematopoietic stem cell transplantation. Disclosures No relevant conflicts of interest to declare.

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Pre-Emptive Therapy with IFN-α-2b for Acute Leukemia Patients with High Risk of Relapsing Tendency Post Allo-HSCT

Blood ◽

10.1182/blood.v128.22.2250.2250 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2250-2250

Author(s):

XiaoWen Tang ◽

Xiaoji Lin ◽

Aijing Wang ◽

Feng Chen ◽

Xiao Ma ◽

...

Keyword(s):

Survival Rate ◽

High Risk ◽

Acute Leukemia ◽

Median Time ◽

Conflicts Of Interest ◽

Disease Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Donor Chimerism ◽

Significant Difference

Abstract Objective: To determine the efficacy and safety of IFN-α-2b pre-emptive therapy for acute leukemia(AL) patients with relapsing tendencies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospectively analyzed 986 acute leukemia patients undergoing allo-HSCT from Jan ,2006 to Mar ,2014 in our hospital. After allo-HSCT, 986 AL patients were periodically monitored the minimal residual disease(MRD) including: bone marrow smear, leukemia-associated immunophenotype (LAIP), leukemia specific or related fusion genes, and donor chimerism through multi-parameter detection to evaluate disease status. Patients were given IFN- a -2b 3 million units / day by subcutaneous injection for preemptive treatment once a relapse tendency was detected, such as: increasing proportion of blast in bone marrowbetween 3-5%, or MRD>1.0×10-3, or leukemia specific fusion gene transfrom negative to positive, or dynamic incressing copy number of WT1 more than 200 copies/104 abl, or decreasing of donor chimerism(≤ 90%). There were 98 patients who presented increasing tendency of MRD and were enrolled in this study. Among them, 31 patients received IFN-α-2b pre-emptive therapy, and 67 patients received non-IFN-α-2b therapy such as: withdraw immunosupressant, traditional DLI or DC-CIK immunotherapy. Results: There were no significant differences in disease characteristics between two groups. For the 31 patients who received IFN-α-2b pre-emptive therapy(IFN group), the median time of IFN-αtreatment was 60 days (range: 5-720 days), Twenty five patients had responsed to the treatment without progressing to hematological relapse (response rate 80.6%). 2 patients developed to hematological relapse again after temporary response; 3 patients had no response and eventually progressed to hematological relapse. Regarding 67patients who received non-IFN-α-2b therapy(non IFN group), 22 patients responsed to the treatment (RR 32.8%), 45 patients failed to the treatment and progressed to hematological relapse at a median time of 35 (range: 6-940) days, There was significant difference of RR between two group(P=0.000) . 31 patients of IFN group tolerate well and no patient terminated therapy due to side effects. During the treatment of IFN, 18 patients(58.1%) developed GVHD: 6 patients (19.4%) with aGVHD and 14 (45.2%) with limited cGVHD . The median follow-up time was 21 (4.5-78.5) months. 22 of 31 cases of IFN group maintained disease-free survival. The 5-year overall survival rate (OS) and the leukemia-free survival rate (LFS) of IFN group were 47.0%±13.9% and 38.7%±13.1% respectively. However, the 5-yr OS and LFS of non IFN group were 14.5%±10.7% and12.5%±9.4% respectively.The difference were significantly (P=0.000,P=0.002 respectively). Patients with GVHD had significantly better response than patients without GVHD (88.9% vs 53.8%, P=0.043, P <0.05). Conclusion: IFN-α-2b pre-emptive therapy can effectively prevent high-risk patients with relapsing tendencies for disease progression post allo-HSCT. Further large-scale investigation is warranted. Disclosures No relevant conflicts of interest to declare.

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The Platelet Millionaire: A Rare Cause of Thrombocytosis in an Adolescent

Blood ◽

10.1182/blood-2019-129278 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5391-5391

Author(s):

Ritika Walia ◽

Theresa Sepulveda ◽

Sharon Wretzel ◽

Philip H Brandt

Keyword(s):

Bone Marrow ◽

Bone Marrow Biopsy ◽

Primary Care Physicians ◽

Conflicts Of Interest ◽

Abdominal Ultrasound ◽

Cell Transplant ◽

Peripheral Smear ◽

Hematopoietic Stem ◽

Marrow Fibrosis

Objectives: Primary myelofibrosis is rare in pediatrics, often manifesting as persistent idiopathic thrombocytosis.Transitions from pediatric to adult medical care can be complicated by workup requiring invasive procedures. J.M., an 18-year-old healthy male, presented for excessive gingival bleeding after wisdom tooth extraction. Workup revealed persistent thrombocytosis to 1,165K, prompting a referral to hematology-oncology. A peripheral smear was notable for many platelets but normal RBC morphology. He had splenomegaly on abdominal ultrasound and a decreased von-Willebrand's activity to antigen ratio, suggesting acquired vWD. A bone marrow biopsy was advised; however, J.M. became lost to follow up for over 9 months owing to self-reported anxiety about the procedure. He remained asymptomatic in this interim until he re-presented to clinic for easy bruising, with no other evidence of bleeding at the time. The biopsy was pursued, revealing hypercellular marrow for age with left shifted granulocytic and erythroid maturation, abnormal megakaryocytes, and 3% blasts. This was consistent with primary early myelofibrosis (PMF), positive for MF-1, CALR, and TP53 mutations and negative for JAK2 and BCR-ABL. He was transitioned to adult hematology, maintained on baby aspirin, and referred for potential allogeneic hematopoietic stem cell transplant (HSCT). PMF is characterized by marrow fibrosis due to secretion of fibroblast growth factor by clonally proliferative megakaryocytes. It is a disease of adulthood, with 67 years being the median age at diagnosis. Only 100 cases have been reported in children, most of which are secondary to AML, ALL or other malignancies.1 Most patients present with complications of extramedullary hematopoiesis or bleeding.2 Diagnosis is suggested by a leukoerythroblastic picture on peripheral smear and confirmed with a bone marrow biopsy "dry tap" revealing marrow fibrosis.3 Prognosis in pediatric PMF is difficult to predict but outcomes tend to be worse;4 TP53 mutation is rare and based on limited adult studies may portend a poorer prognosis.5 Our young patient with this rare mutation was therefore referred for HSCT evaluation. Further complicating this case was J.M.'s anxiety, which delayed definitive diagnosis by biopsy. He only agreed to it when, at the med-peds clinic, the concept of local pain management was discussed. Anticipation of upcoming procedures by primary care physicians and close follow-up is especially important for patients transitioning from pediatric to adult providers. Disclosures No relevant conflicts of interest to declare.

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Busulfan/etoposide--initial experience with a new preparatory regimen for autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia

Blood ◽

10.1182/blood.v81.2.319.319 ◽

1993 ◽

Vol 81 (2) ◽

pp. 319-323 ◽

Cited By ~ 47

Author(s):

NJ Chao ◽

AS Stein ◽

GD Long ◽

RS Negrin ◽

MD Amylon ◽

...

Keyword(s):

Bone Marrow ◽

Complete Remission ◽

Median Time ◽

Relapse Rate ◽

Disease Free Survival ◽

Autologous Bone Marrow ◽

Free Survival ◽

Acute Nonlymphoblastic Leukemia ◽

Disease Free

Abstract Current intensive chemotherapy for acute nonlymphoblastic leukemia (ANLL) results in a complete remission in the majority of patients. Unfortunately, the duration of remission is short and most of the patients will experience a relapse of their underlying disease. Autologous bone marrow (BM) transplantation is being explored as a treatment modality designed to improve relapse-free survival. We have conducted a phase II trial exploring the combination of busulfan (16 mg/kg) and etoposide (60 mg/kg) in an attempt to improve antitumor efficacy using this novel preparative regimen. To date, 50 patients (48 with ANLL and 2 patients with biphenotypic acute leukemia) have been treated. The first 20 patients received unmanipulated BM; 28 patients subsequently received 4-hydroperoxycyclophosphamide (4–HC) (60 micrograms/mL)-purged bone marrow, and 2 patients with biphenotypic acute leukemia received both 4–HC (60 micrograms/mL) and etoposide (5 micrograms/mL)-purged BM. Thirty-four patients were in first complete remission (CR1), 12 patients in second complete remission (CR2), and 4 patients in relapse. The median time from first complete remission to BM harvest was 3 months (range, 0.8 to 4) compared with median time of 2 months (range, 1.5 to 5.0) for patients in second complete remission. The median time from harvest to transplant was 1 month for both groups (range, 0.4 to 36). A median of 0.7 x 10(8) (range, 0.2 to 1.4) mononuclear cells were infused. Patients achieved an absolute neutrophil count of > or = 500/microL at a median of 26 days (range, 13 to 96), an untransfused platelet count > or = 20,000/microL at a median of 56 days (range, 15 to 278) and a sustained hematocrit > or = 30% at a median of 50 days (range, 19 to 116). Twenty-six patients are alive and in continued CR. Follow-up of the surviving patients ranged from 6 months to 66 months with a median follow-up of 31 months. Patients receiving purged BM have an actuarial disease-free survival of 57% with a relapse rate of 28% compared with patients receiving unpurged BM whose actuarial disease-free survival is 32% with a relapse rate of 62% (P = .06 for relapse rate). The most significant extramedullary toxicities for this regimen are hepatic and cutaneous (including mucositis). The BU/VP-16 regimen is associated with a significant proportion of patients surviving disease free, especially in the group receiving purged BM. Whether this regimen offers a substantial improvement in disease-free survival over currently used regimens will require a prospective randomized study.

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