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  • 1
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 2192-2192
    Abstract: Introduction The use of Haploidentical Transplantation (haploSCT) with pos-transplantation cyclophosphamide (PTCy) has become in a very good alternative for patients with acute leukemia who need a transplant but without a well matched donor, however, it is not clear what is the "best" conditioning regimen in this setting; on the other hand, fludarabine + melphalan (flu-mel) is a well-known preparative protocol, it has a good balance between toxicity and anti-leukemic activity. We explored the use of it plus the addition of 200-400cGy of total body irradiation (TBI) in a group of 34 patients with acute leukemia who were allografted with haplo peripheral blood stem cells (PBSC) and PTCy. Methods and Patients Donors were mobilized with filgrastim 5 mg/kg/BID for five days, the PBSC were collected with one or two large volume apheresis procedure. The conditioning consisted of melphalan 100-120 mgs/m2 administered on day -6, fludarabine 150 mgs/m2 split in 5 days, and 200-400 cGy of TBI added on day - 1 (Flu Mel TBI). All patients were given PTCy 50 mg/kg/day on D+3 and D+4, followed by ciclosporin and mycophenolate starting on day + 5. In all cases filgrastim was administered after transplant beginning on d + 6. After a signed informed consent, 34 patients underwent to transplant; median age was 22 years (range 5-53), the diagnosis were: acute myeloid leukemia 11 patients, acute lymphoid leukemia 22 and 1 had myelodysplasia. 26.5% were in first remission (CR1), 47 % in second (CR2), and 26.5% in third or with more than 5% of blast in bone marrow (CR3). 5 out of 30 cases in remission had MRD positivity Results 50% of patients received flu-mel +TBI 400 cGy, while the other half were given flu-mel + TBI 300 or 200 cGy. A mean of 12 million of PBSC/kg was infused. The neutrophil engraftment rate was 97%, median time to achieve 500 or more was 15 days (range 11-20), 3 patient died before d+ 100 without platelet recovery, the remaining had a self- sustained platelet count of 20.000 or more at an average of 15 days (range 12-48). Chimerism was available in all cases that survived beyond day + 100; all of them had full donor hematopoiesis. The main toxicities were gastro intestinal; mucositis G II-III 35%, and two cases of hemorrhage, and bacteremia (30%). With a median follow-up for surviving patients of 11 months, the incidence of GVHD acute (GII-IV) and chronic extensive was 29.4 and 25% respectively. The transplantation related mortality was 17.4% while the rate of relapse was 14%. Causes of death were relapse: 4, sepsis: 4 fusariosis: 1, intestinal GVHD: 1. Event was defined as death for any cause or relapse, the event free survival (Kaplan Meier) at 12 and 24 months was; 63% for the whole group, 73% for CR1+CR2 and 31% for patients in CR3 or with active disease (figure 1) Conclusion The use of fludarabine - melphalan plus 200-400 cGy of TBI as a preparative regimen previous to transplant of haplo PBSC with PTCy was associated to a fast and almost universal engraftment, acceptable toxicity and encouraging disease free survival showing a very good balance between tolerance and anti leukemic activity. It deserve more studies Figure 1 Event free survival according remission Figure 1. Event free survival according remission Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 2
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1916-1916
    Abstract: Fludarabine 120-160 mgs/m2 plus melphalan 140 mgs/m2 (Flu- Mel) is a well known reduced intensity conditioning protocol used in allogeneic transplantation, however it can be no enough intense to treat high risk acute leukemia, specially in the relapse setting. On the other hand, 400 cGy of total-body irradiation (TBI 400) has been successfully added to myeloablative dose of fludarabine busulfan without excessive toxicity. We designed a regimen adding TBI 400 to usual dose of Flu-Mel with the idea to increase its anti-leukemic activity. Below we present our experience Methods and patients Peripheral blood stem cells were mobilized with figrastim for 5 days, later, 1 or 2 apheresis were done to achieve a minimum of 3 million of CD34 + cells/kg. The conditioning consisted of fludarabine 30-40 mgs/m2 for four days, melphalan 140 mgs/m2 one dose, on day - 1, TBI 400 was administered split in 2 fractions. The prophylaxis against graft versus host disease (GVHD) was done with cyclosporine and methotrexate, all patients were given pegfilgrastim 22 patients were transplanted, median age 26.5 years (range 8-49), the diagnosis were; acute lymphoblastic leukemia (13), acute myeloid leukemia (6), chronic myeloid leukemia (1), high risk myelodisplasia(1), mixed acute leukemia(1). 32% were in first remission, 41% in second, 27% were in third or they had active disease. The discrimination according CIBMTR disease risk index (CIBMTR-DRI) was: 54% high risk, 41% intermediate and 5% low Results All donors were matched siblings, a median of 10 millions/kg of CD34+ cells were infused; all patients engrafted, the neutrophil and platelet recovery occurred on days +11 and + 14 respectively. The grade III toxicity was; mucositis, 45% and one case of encephalopathy, there were not any case of sinusoidal obstruction syndrome. The incidence of GVHD acute (GII-IV) and chronic extensive was 10 and 25%. With a median follow up of 11 months (range 6-30) the overall survival (OS)(Kaplan-Meier) at 24 and 36 months is 69 and 55% . Six patients have died, one due to sepsis and five secondary to relapse. The OS according to CIBMTR-DRI at 36 month was 75 and 46% for intermediate and high risk groups Conclusion: The addition of TBI 400 to Flu- Mel regimen is feasibly, the main toxicity is mucositis, the non- relapse mortality is very low and the incidence of GVHD, acute a chronic, is not higher than expected This combination shows an encouraging anti leukemic effect, as it is demonstrated by an OS of 75 and 46% in patients classified in intermediate and high risk CIBMTR DRI groups. This preparative protocol can be a low toxicity alternative to more conventional myeloablative regimen. It warrants further studies Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3118-3118
    Abstract: Introduction: T cell replete haploidentical stem cell transplantation with post-transplantation cyclophosphamide (PTCy) has shown encouraging results for the treatment of hematologic malignancies, its main advantage is that almost every patient will have a donor in a timely manner. However this technique has been explored mainly in adults and using bone marrow as a cellular source. Here we present our experience using T cell replete haploidentical peripheral blood stem cell transplantation (TCR-Haplo-PBSCT) with PTCy in 21 pediatric patients whit high-risk acute leukemia Methods and Patients: Donors were mobilized with filgrastim 5 mg/kg/BID for five days, the PBSC were collected with one large volume apheresis procedure. The conditioning consisted of fludarabine 30 mg/m2/day for 5 days, oral busulfan 4-8 mg/kg/split in 1-2 days and, one day before transplant, total body irradiation 400 cGy divided in two fractions (Flu Bu TBI) or fludarabine 150 mgs/m2 split in 5 days, melphalan 100-140 mgs/m2, one day and TBI 200-400 cGy on day - 1 (Flu Mel TBI). All patients were given PTCy 50 mg/kg/day on D+3 and D+4, followed by ciclosporin and mycophenolate starting on day + 5. In all cases filgrastim was administered after transplant beginning on d + 6. After a signed informed consent, 21 patients who needed an urgent transplant, were allografted; median age was 11 years (range 1-16), 10 were girls, the diagnosis were: acute lymphoblastic leukemia 11 patients, acute myeloid leukemia 9, and blastic phase of chronic myeloid leukemia one. 19% were in first remission (CR1), 43% in second (CR2), and 39% in third or with refractory disease(CR3). Results: 17 patients were given Flu Bu TBI conditioning while 4 received Flu Mel TBI combination All the donors shared 4 out of 8 alleles with the recipient; in 62% of the cases the donor was the Mother in 19% the Father and in other 19% one sibling. A median of 16 million of CD34+ cells/kg was infused. The engraftment rate was 100%, median time to achieve 500 neutrophil or more was 15 days (range 14-20), 1 patient out of 21 died without platelet recovery, the remaining had a self- sustained platelet count of 20.000 or more at a median of 14 days (range 10-21). Chimerism at day + 100 was available in 19 cases; all of them had full donor hematopoiesis. The median follow-up is 11 months (range 3-28), the cumulative incidence of graft versus host disease (GVHD) acute grade II-IV and chronic extensive was 23.8% and 25% respectively. Six patients have died, the causes were; pneumonia (n:1) and relapse of leukemia(n:5). In table 1 is presented the overall survival (OS) and event free survival (EFS) for the whole group and discriminated according remission Table 1.Whole groupCR1CR2CR3OS month 1277.4% ± 10100%100%47.3% ± 18.8EFS month 1271.5% ± 10.9100%100%43.8% ± 18.8OS month 2469.6% ± 11.6100%80% ± 17.947.3% ± 18.8EFS month 2463.6% ± 12.3100%83% *22 months21.9% ±18.1 Conclusion: The use of TCR-Haplo-PBSCT with PTCy and a medium intensity conditioning for treating pediatric high risk acute leukemia is promising; it is associated with very good engraftment rate, low transplantation related mortality and an acceptable incidence of GVHD despite the use of peripheral blood. This protocol produces a remarkable leukemia free survival rate, especially in patients in CR1 and CR2. This approach could be a good alternative for children with high-risk leukemia and without suitable matched donors. It deserve further studies Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 4
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 849-849
    Abstract: Storage of peripheral blood stem cells (PBSC) at 4ºC is a simple and inexpensive alternative to cryopreservation for preserving the clonogenic capacity of progenitors cells in the autologous transplant setting, however it has been perceived as unsafe and has deserved little attention. We present the experience of two Latin-American centers using refrigerated, non-cryopreserved stem cells after conditioning with high dose melphalan, CBV or BEAM in a large group of lymphoma and myeloma patients Materials and Methods PBSC were mobilized with filgrastim 5 mg/kg/BID for three to six days.One to three apheresis procedure were employed; the cells were stored at 4ºC for 5 to 6 days in patients who received BEAM or CBV and for 3 days in those given melphalan. All of the conditioning regimens were administered preserving the full intensity of dose (Table 1). After the autograft all patients received filgrastim or pegfilgrastim Table 1 BEAM D-5 D-4 D-3 D-2 D-1 BiCNU 300 mgs/m2 X Etoposide 200-400 mgs/m2 X X X X Citarabine 300-400 mgs/m2 X X X Melphalan 140 mgs/m2 X CBV BiCNU 300 mgs/m2 13 patients received carboplatin 900 mgs/m2 instead BiCNU X Etoposide 300 mgs/m2 X X X Ciclophosphamide 2.000 mgs/m2 X X X Melphalan Melphalan 200 mgs/m2 X Melphalan 100 mgs/m2 X X Results 102 lymphoma patients: 48 Hodgkin`s lymphoma (HL) and 54 non-Hodgkin´s lymphoma (NHL) received BEAM (71) or CBV (31). A median of 3.3 millions/kg of CD34 was infused; the median viability of the cells after 5-6 days of refrigeration (trypan blue exclusion) was 82%. 101 out of 102 patients engrafted, median time to achieve 500/ul neutrophil or more was 12 days, 100 were evaluable for thrombopoiesis, 99 of them had a self- sustained platelet count of 20.000 or more at a median of 17 days. The OS at 5 years was 59% and 42% for patients with Hodgkin and lymphoma respectively 151 patients with multiple myeloma received melphalan 200 mgs/m2. After 72 hours of refrigeration, a median of 2.6 millions/kg of CD34 cells were infused, the viability in all cases being 〉 90%. Three patients were not evaluable because early death. Median time to achieve 500 neutrophil or more and 20.000 platelets was 12 (9-50) and 15 (7-50) days. The OS at 5 years was 50% 21 patients with NHL and HL received as conditioning regimen melphalan 200 mgs/m2. After 72 hours of storage, a median of 1.75 millions/kg of CD34 cells were transplanted, 100% of them engrafted, median time to 500 neutrophils and 20.000 platelets was 11.9 and 15 days respectively There were no cases of secondary engraftment failure in any of the three groups Conclusion In this series of 268 patients, we have shown that autologous PBSC can be kept at 4ºC in a conventional blood bank refrigerator for up to six days and use them to rescue high-dose chemotherapy in both multiple myeloma and lymphoma patients. Avoiding freezing procedures results in substantial cost savings. The availability of freezing devices for hematopoietic stem cells is not anymore an obstacle to start a an autologous transplantation program This observation is critical in areas of underprivileged economic circumstances, where more than 50% of the inhabitants of the world live. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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