Allogeneic Stem Cell Transplantation for CML in Accelerate or Blastic Phase

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1220-1220 ◽  
Author(s):  
Elena V Morozova ◽  
Tatjana Zabelina ◽  
Francis Ayuk ◽  
Christine Wolschke ◽  
Thomas Stübig ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Blastic Phase ◽  
Cd34 Cells ◽  
Cell Source ◽  
Reduced Intensity

Abstract Patients with advanced chronic myeloid leukemia (CML) in accelerate (AC) or blastic phase (BC) have a dismal prognosis despite the use of tyrosine kinase inhibitors (TKI). Here we report our experience for allogeneic stem cell transplantation (ASCT) in advanced and phase of CML. Between July 1990 and May 2012 88 patients with a median age of 36 years (range 7-76) received allogeneic stem cell transplantation from related (n=34) or unrelated (n=54) donors , including 19 HLA-mismatched donors after myeloablative (n=54) or reduced intensity (n= 34) conditioning. Stem cell source was bone marrow (n=37) or peripheral blood stem cells (n=51). GvHD prophylaxis consisted of calcineurin inhibitor plus short course MTX or MMF. Most of the patient received additional ATG as GvHD prophylaxis (84%).The majority of patient (75%) received TKIs before ASCT. 50% received one TKI, 8 received 2 TKIs and 2 received 3 TKI before ASCT. At time of transplantation 34 patient achieved a second or subsequent chronic phase, 28 were in accelerate and 25 in blastic phase. Overall the median number of blasts at time of ASCT was 18.75% (range 5-58%) and the time from diagnosis to transplantation was 27 months (range 3-296). No primary graft failure was observed. The incidence of acute graft versus host disease (GvHD) grade II to IV was 43% and of severe grade III/IV GvHD was 28%. Forty-two percent of the patient experienced chronic GvHD. The non-relapse mortality (NRM) at 1 and 5 years was 22% (95% CI; 14-30%) and 23% (95%CI: 13-33%), respectively. In a multivariate analysis (MVA) only higher number of transplanted CD34+ cells were associated with a lower risk of NRM (HR 0.850, 95%CI: 0.729-0.992, p=0.04). The cumulative incidence of relapse at 5 years was 43% (95% CI: 31-55%). In a MVA age > 40 years (HR 2.272, 95%CI: 1.112-4.645, p=0.024) and Reduced intensity conditioning (HR 2.034, 95%CI: 0.998-4.144, p=0.051) were significant factors for higher risk of relapse. After a median follow-up of 91 months (r., 52-133) the estimated 5 and 10 year overall survival was 44% (95% CI: 32-56) and 40% (95% CI: 28-52%), respectively. In an univariate analysis overall survival was significantly influenced by stem cell source, gender, CD34 transplanted cell number and blastic phase at time of transplantation. However, the only significant factor for improved survival in a MVA was a higher number of transplanted CD34+ cells (HR 0.916, 95%CI: 0.844-0.916, p=0.038). Disclosures No relevant conflicts of interest to declare.

Reduced-Intensity Cord Blood Transplantation in Adult Patients for the Recurrence after Allogeneic Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5346-5346
Author(s):  
Sachiko Seo ◽  
Naoyuki Uchida ◽  
Hisashi Yamamoto ◽  
Naofumi Matsuno ◽  
Yoshiko Matsuhashi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Stem Cell Source ◽  
Cell Source ◽  
Conditioning Regimens ◽  
Reduced Intensity

Abstract Backgrounds: For more than 10 years, umbilical cord blood has become an alternative stem cell source for the patients with hematological malignancies requiring allogeneic stem cell transplantation. Cord blood transplantation (CBT) can be performed more quickly than other stem cell transplantation, since cord blood units are preserved in the deep freeze and 1–3 HLA mismatched donors are acceptable. Considering these advantage, we examined the feasibility of cord blood transplantation using reduced-intensity regimens (RI-CBT) for adult relapsed patients after allogeneic tranplantation. Patients/methods: We reviewed medical records of 26 patients who received RI-CBT at Toranomon Hospital between November 2003 and June 2006. Median age of the patients was 36 years (range, 20–66). Underlying diseases were acute leukemia (n=17), myelodysplastic syndrome (n=4) and lymphoma (n=5). The stem cell source of the first transplantation were bone marrow from sibling donor (n=2), bone marrow from unrelated (n=5) donor, peripheral blood stem cell from sibling donor (n=5) and unrelated cord blood (n=14). Conditioning regimens comprised fludarabine 125–180 mg/m2 in several combination with melphalan 80–140 mg/m2, Busulfan 8–16mg/kg and total body irradiation (TBI) (4–8 Gy). Graft-versus-host disease (GVHD) prophylaxis was cyclosporine (n=5) or tacrolimus (n=21). Median number of total nucleated cells and CD34+ cells was 2.56×106 cells/kg (1.91–5.94), and 0.86×105 cells/kg (0.57–1.77) respectively. HLA disparities were 5/6 (n=2), 4/6 (n=22), and 3/6 (n=2). Results: Median observation period was 58 days (range, 32–380). Overall survival for 1 year was 15% and 16 patients were died of disease progression (n=5) and infection (n=11). The infection in 4 patients was considered to be caused by regimen related toxicity (RRT). No grade IV toxicities (NCI-CTC Ver.3.0) were observed. The duration between two transplantations was longer in surviving patients compared to dead patients (98 days (range, 39–2108) and 262 days (range, 95–901), respectively), although significant difference was not detected. The stage of the disease in the second transplantation, conditioning regimens and HLA disparities did not influence to the outcome. Discussion: We demonstrated that RI-CBT could be an available and feasible treatment for the relapsed patients after stem cell transplantation. Moreover, the RRT is acceptable even in the patients with an advanced disease.

Impact of Stem Cell Source on Outcome of Allogeneic Stem Cell Transplantation in Pediatric Cancer

2020 ◽  
Vol 37 (1) ◽  
pp. 117-125
Author(s):  
Hammad ، Mahmoud ◽  
Rashad , Hanaa ◽  
Hafez , Hanafy ◽  
Abdallah , Amr ◽  
El Sharkawy , Nahla ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Pediatric Cancer ◽  
Stem Cell Source ◽  
Cell Source

Related Vs Unrelated Donors After Auto-Allo Tandem Stem Cell Transplantation for Newly Diagnosed Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1201-1201
Author(s):  
Nicolaus Kröger ◽  
Tatjana Zabelina ◽  
Marion Heinzelmann ◽  
Georgia Schilling ◽  
Christine Wolschke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donor ◽  
Newly Diagnosed ◽  
Stem Cell Source ◽  
Cell Source ◽  
Unrelated Donors

Abstract Abstract 1201 Poster Board I-223 Introduction: Autologous stem cell transplantation followed by a dose-reduced conditioning and allogeneic stem cell transplantation from HLA-identical siblings has become a treatment option for patients with multiple myeloma. However, only a minority of the patients with multiple myeloma has an HLA-identical sibling and the experience using unrelated donor in this setting is limited. Patients and Methods: From 1997 to 2007, 73 patients (male:45; female:28) with multiple myeloma stage II/III and a median age of 49 years (r, 29-64) were included in a prospective trial to determine the efficacy of a tandem auto-allogeneic stem cell transplantation SCT) from HLA-identical sibling (n=24) or unrelated donors (n=45). Unrelated donor were either fully HLA matched (n=29) or had one mismatch (n=16).Deletion 13q14 could be analyses in 64 pts was found to be positive in 66% of the pts. Del13q14 was more present in patient with unrelated (n=42) than with related (n=22) donors. Stem cell source was PBSC (n=69) or bone marrow (n=4). Induction-chemotherapy consisted of a median of 4 cycles anthracycline-based therapy in 60 pts, or of thalidomide- (n=3) or bortezomib- (n=8) based regimen. 6 pts did not respond to induction therapy and received salvage chemotherapy before autologous SCT. Conditioning prior auto SCT consisted of melphalan 200mg/m2. After a median of 110 days (range 39-228) patients received a reduced intensity regimen with melphalan (140 mg/m2)/fludarabine regimen followed by allogeneic SCT from related (n=24) or unrelated (n=45) donors. GvHD prophylaxis consisted of anti-lymphocyte globulin (ATG-Fresenius®), cyclopsorin A and short course of MTX. Results: No primary or secondary graft failure was observed and leukocyte engraftment was achieved after a median of 15 days (range, 9-27), respectively. Acute graft-versus-host disease (GvHD) grade II to IV occurred in 38% and chronic GvHD in 22% of the patients. Limited GvHD was seen in 16 % and extensive GvHD was seen in 6 % of the patients. There was no difference regarding incidence of GvHD between HLA-identical sibling and unrelated donors. Overall response rate at day 100 was 94% including 55% complete remission (CR) and did not differ between related and unrelated SCT. Cumulative incidence (CI) of non-relapse mortality at one year was 20% (95% CI:11-29%) and did not differ between MUD and MRD (21 vs 17%, p 0.35). The cumulative incidence of relapse at 3 and 5 years was 30% (95% CI:19-41%) and 42% (95% CI: 29-55%), respectively with no difference between related and unrelated SCT at 5 years: 36 vs 44%(p= 0.6). The only significant factor for higher relapse incidence at 5 years was the presence of del13q14 (60 vs 20%, p= 0.007). After a median follow up of 40 months (r., 26-100), the estimated 5-year progression-free (PFS) and overall survival (OS) rates were 31% (95%CI: 19-43%) and 54% (95% CI: 42-64%), respectively, with no difference between related and unrelated SCT. Due to the higher relapse incidence only presence of del13q resulted in a significant worse 5- year OS and DFS (45 vs 77%, p=0.02 and 18 vs 57%, p=0.04). Conclusions: Unrelated donors as stem cell source for auto-allogeneic tandem stem cell transplantation for newly diagnosed myeloma patients resulted in similar NRM, relapse-incidence, DFS and OS than HLA-identical sibling transplantation and can therefore be used as alternative stem cell source. Outcome after transplantation is better for patients lacking del 13q14. Disclosures: No relevant conflicts of interest to declare.

Single-Institute Analysis of Allogeneic Stem Cell Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5445-5445
Author(s):  
Takeshi Kobayashi ◽  
Takuya Yamashita ◽  
Miwa Sakai ◽  
Yoshiki Okuyama ◽  
Kazuteru Ohashi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Stem Cell Source ◽  
Cell Source

Abstract Purpose We report the outcomes of allogeneic stem cell transplantation (SCT) for the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in a single center. Patients and Methods Between August 1993 and March 2005, 36 patients with Ph+ALL received SCT at Tokyo Metropolitan Komagome Hospital. The median age was 41 years (range; 17 to 60 years). All patients received myeloablative conditioning regimen (cytosine arabinoside, cyclophosphamide and fractionated 12Gy total-body irradiation). Stem cell source of SCT was 14 related donors (bone marrow [n=9] and peripheral blood stem cell [n=5]) and 22 unrelated donors (bone marrow [n=13] and cord blood [n=9]). Results Seventeen (47%) of 36 patients are alive at a median of 2.16 years (range; 1.0 to 3.3 years) after transplantation. Three years overall survival (OS) and disease free survival (DFS) for all patients are 42.3% and 35.4%, respectively. Three years OS and DFS are 55.4% and 46.4% for the 24 patients in complete remission (CR) at transplantation, while 36.4% (p<0.001) and 16.7% (p<0.01) for the 12 patients in non-CR, respectively. Stem cell source and patients age do not affect the outcomes. The higher white blood cell counts at diagnosis are associated with poor OS (p=0.003). The median duration from diagnosis to SCT is 7 months (range; 3 to 29 months). Three years OS of the patients who received SCT within 7 months from diagnosis is better than that of the others (59.3% vs. 31.1%, p=0.019). Conclusion This analysis suggests that shorter duration between diagnosis and transplantation improve the clinical outcomes of SCT for Ph+ALL, especially performed in CR.

Comparison of Cyclosporine A and Mycophenolate Mofetil vs Cyclosporine A and Methotrexate in Reduced Intensity Conditioning HLA Sibling Allogeneic Stem Cell Transplantation. A Case-Match Single-Center Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4994-4994
Author(s):  
Jose L. Piñana ◽  
David Valcárcel ◽  
Rodrigo Martino ◽  
Rocio Parody ◽  
Anna Sureda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mycophenolate Mofetil ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cyclosporine A ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Reduced Intensity Conditioning ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity

Abstract BACKGROUND: Graft-versus-host disease (GVHD) is the major obstacle to successful allogeneic stem cell transplantation (SCT) transplantation. Cyclosporine (Csa) in combination with methotrexate (MTX) is the most commonly used prophylactic regimen. The combination of CsA and Mycophenolate Mofetil (MMF) has recently been introduced. In this case-match study we retrospectively analyzed the introduction of MMF as GVHD prophylaxis in comparison with a short course of MTX in the setting of reduced intensity conditioning allogeneic SCT (Alo-RIC). PATIENTS AND METHODS: We analyzed 59 Alo-RIC recipients who received an Alo-HSCT from an HLA-identical sibling between April 2000 and June 2006. The median follow-up for the whole group was 473 days (8 to 2139 days). The study group included 40 males and 19 females. Median age was 59 years (range 43 to 72). Diagnoses were acute leukemia/myelodisplastic syndrome) (n=19/22), mutiple myeloma (n= 6), chronic myeloid leukemia (n=5) and non- Hodgkin lymphoma (NHL) (n= 4). GVHD prophylaxis consisted of Csa/MTX (MTX group) in 37 patients and Csa/MMF (MMF group) in 22 patients. The conditioning regimen was based on fludarabine in combination with busulfan (42 recipients) or melfalan (17 cases). RESULTS: The occurrence of mucositis grade 2–4 was higher in the MTX group than in the MMF group (62% vs 28% p= 0.015). No significant differences were found between MMF vs MTX groups in time to neutrophil recovery (16 +/−3 days vs 15 +/− 2days) (p= 0.5). Median time to the achievement of complete T-cell donor chimerism in the MTX and MMF groups was 79 days (range 19–740) and 76 days (range 24–223) respectively (P=0.4). The 1- year non-relapse mortality was similar in MTX and MMF groups 14% (95% C.L. 6–31%) vs 28% (95% C.L. 13–60%) respectively; P=0.2. Cumulate incidence of acute GVHD for MTX and MMF groups was 49% (95% C.L. 35–68%) and 68% (95% C.L. 51–91%) respectively (P= 0.6). Patients in the MTX group showed a trend to a higher incidence of chronic GVHD than the Csa/MMF group, 55% (95% C.L. 40–74%) vs 42% (95% C.L. 23–75%) (P=0.2). No differences were found between MTX vs MMF groups in 1-year overall survival [78%(64–92%) vs 53%(38–76%); P=0.1] nor in 1-year relapse incidence [37% (95%CI 21–64%) vs 19% (95%CI 10–37%) P=0.1) We conclude that the Csa/MMF combination appears to be equivalent to the standard Csa/MTX aGVHD prophylaxis in Alo-RIC. MMF showed significantly less mucositis.

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