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Haematopoietic Stem Cell Transplant Outcomes in Patients with Thalassemia Major from a Tertiary Care Center in South India.
Abstracts / Biol Blood Marrow Transplant 26 (2020) S96 S255
Financial Support: To provide free BMT, Airport Authority of India and Bina Refinery provided financial support through corporate social responsibility. Conditioning Regimen: Majority of patients (pts) received rATG-6mg/kg, FLU-150mg/m2, BU-12.8-16mg/kg (without PK studies) and cytoxan-200mg/kg. Prophylaxis; aGVHD: CSA/MTX. Acyclovir until day 100. Fluconazole until ANC >1000/mm3. Bactrim for PCP. G-CSF was not routinely administered. Follow-Up: Pts stayed in the hospital vicinity for up to 6 months post-BMT. The majority of outpatient medications were also provided free of charge. Results: Donors: 13F and 7M, median age 8 yrs (2-18). The median number of CD34+ cells harvested from bone marrow was 5.5 £ 106/kg (1.5-21.6); only 2 donors were G-CSF mobilized. Patients: First BMT was conducted in April 2018. Median FU 9 months (3-17). Of the first 20 pts, 12 were males. Pts were ages 2-5Y (n=9), 5-10Y (n=8) and >10Y (n=3). 19/20 pts were heavily transfused. Thalassemia spectrum (16/20), SCD (n=1), MDS (n=1), SAA (n=1), and CML (n=1). 4 pts with major ABO incompatibility underwent RBC desensitization. Median time for ALC >500/mm3, neutrophil and platelet engraftment was 19d (12 -30), 27d (14-33) and 25d (15-50), respectively. Two pts had graft failure (one died). At last follow up, two pts have stable mixed chimerism and 16 (80%) have donor chimerism >90%, all 18 engrafted pts are transfusion independent. Overall survival is 95%. The median cost of BMT was $11,000 ($6,000-22,000). Conclusion: Early results demonstrate the feasibility of our model. With appropriate remote supervision and dedicated general pediatricians and nurses with limited BMT training, we can successfully conduct MSD BMT in a resource-constrained set up. Despite living in remote villages, poverty, facing socio-cultural challenges, families can be trained to provide appropriate care at home. Multi-drug resistant bacteraemia and GI infections remain a major concern. Incidence Mucositis grade III-IV
0%
Bacteraemia
45%
CMV viremia
25%
ADV/ EBV viremia
0%
VZV reactivation
20%
Dengue
5%
Fungal infection
5%
GI parasitic infections
80%
Moderate-severe VOD
0%
PRES
0%
Grade II-IV aGVHD
5%
S217
322 Haematopoietic Stem Cell Transplant Outcomes in Patients with Thalassemia Major from a Tertiary Care Center in South India. Sunil Bhat1, Nataraj KS DM2, Shobha Badiger3, Annapandian Vmacademic research4, Sharat Damodar5. 1 Pediatric Hematology, Oncology and Bone marrow transplantation, Mazumdar Shaw Cancer Center, Narayana Health City, Bangalore, Bangalore, India; 2 Haematology, Mazumdar Shaw medical center, Bangalore, India; 3 Mazumdar Shaw Cancer Center, Narayana Health Center, Bangalore, Bangalore, India; 4 Narayana hrudayalaya foundations, Bangalore, India; 5 Department of Haematology, Mazumdar Shaw Cancer Center, Bengaluru, India Background: Hematopoietic stem cell transplant (HSCT) is widely used as a gene replacement therapy in Thalassemia patients for decades. Survival probabilities after HSCT have increased considerably with advancements in graft versus host disease (GVHD) preventive strategies and conditioning regimens. Here we report our HSCT experience in patients with Thalassemia major, with different graft sources, in terms of transplant outcomes such as neutrophil and platelet engraftment, acute and chronic graft versus host disease (GVHD), thalassemia free survival and overall survival. Methods: We analysed the data of 164 Thalassemia patients who have undergone HSCT between Jan-2012 to Jun-2019 at our centre. We evaluated the demographic and clinical characteristics of patients, graft source on the HSCT outcomes, such as engraftment, graft versus host disease, day-100 survival, thalassemia-free survival and overall survival. Results: Out of 164 patients, 100 (61%) were males, the mean age was 9.47§4.41 (range, 1 -24) years. Peripheral blood stem cell (50%) and bone marrow (47%) are the respective graft sources with predominant matched sibling donor transplants (60.4%). One third of the patients received Fludarabine/Busulfan/Cyclophosphamide based conditioning regimen. Twentyeight percent of the patients developed acute GVHD (grades IIV) and 7.3% developed chronic GVHD. The average time to neutrophil engraftment was 14 (range, 8-24) days and platelet engraftment was 18 (range, 8-72) days. The average time to neutrophil engraftment and platelets engraftment did not
Figure 1. Basic demographics and clinical details of the study patients based on HLA-donor type
S218
Abstracts / Biol Blood Marrow Transplant 26 (2020) S96 S255
significantly differ between the HLA-donor type (Figure 1). There were 26 deaths (15.9%) and 7 (4.3%) graft rejections during the follow-up. Infections are the major cause of deaths. The day 100 survival was 89%, the overall survival was 84% and the thalassemia free survival was 74.4%. Conclusion: HSCT with various preparative regimens, GVHD preventive strategies, and varied graft sources is certainly a unique curative option for the Thalassemia major patients in the developing world. The survival after HSCT in Thalassemia patients are similar regardless of stem cell source, donor-HLA type (Figure 2) and GVHD (Figure 3). However, the incidence of GVHD is more with matched unrelated donors.
Figure 2. Overall survival functions of Thalassemia patients after Haematopoietic stem cell transplantation based on HLA-match
Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH Introduction: We wanted to study the role of abatacept on the incidence of graft versus host disease (GVHD) in patients with sickle cell disease (SCD) undergoing allogeneic hematopoietic stem cell transplant (HSCT). Methods: We conducted a retrospective chart review of patients who received an allogeneic HSCT for SCD at Cincinnati Children’s Hospital Medical Center and compared various transplant characteristics between patients with and without abatacept for acute GVHD prophylaxis. Results: Sixteen patients were transplanted for SCD at our center. Nine patients received a calcineurin inhibitor, methotrexate and abatacept at 10 mg/kg intravenously on days -1, +5, +14 and +28 while 7 patients received a calcineurin inhibitor with methotrexate and methylprednisolone for acute GVHD prophylaxis (table 1). No abatacept infusion related adverse effects were observed. Neutrophil engraftment was comparable at a median of 12.5 days (range 11-21) in patients without abatacept versus 13 days (range 12-16 days) in the abatacept cohort. Incidence of grade 2-4 GVHD was 0/9 in the abatacept cohort versus 3/7 patients in the no-abatacept cohort. Two of the 3 acute GVHD patients in the no-abatacept cohort had visceral involvement. One patient in the abatacept cohort had mild chronic GVHD compared to 3 patients in the no-abatacept cohort with mild (n=1) and moderate (n=2) chronic GVHD. Six patients in the no-abatacept cohort had viral reactivation compared to 8/9 patients in the abatacept cohort. No patient in either cohort had viral disease. One patient in the abatacept cohort had secondary graft loss and was transplanted again with the same donor and conditioning regimen successfully. There was no graft loss in patients who did not receive abatacept. The disease-free survival was 100% in both groups at last follow up of 1925 days (range 837-8164 days) in the no-abatacept group and 770 days (range 112-1634 days) after HSCT in the abatacept cohort. Conclusions: Abatacept is well tolerated and decreases the incidence of acute and chronic GVHD in children with SCD undergoing fully matched sibling transplants. Larger studies are needed to definitively determine the impact of abatacept in GVHD prophylaxis in the matched sibling donor setting.
Table 1 Patient demographics
Figure 3. Effect of GVHD on overall survival functions of Thalassemia patients after Haematopoietic stem cell transplantation
323 Abatacept Decreases the Rate of Acute and Chronic Gvhd in Children with Sickle Cell Disease Undergoing Matched Sibling Transplants Ruby Khoury1, Michael S. Grimley MD2, Stella M. Davies MBBS, PhD3, Pooja Khandelwal MD1. 1 Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; 2 Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; 3 Division of
324 Haploidentical Stem Cell Transplant with Post-Transplant Cyclophosphamide with Busulfan, Fludarabine and Thiotepa Conditioning for Children with Thalassemia Major Satya Prakash Yadav MBBS, DCH, DNB, Anil Sharma, Rohit Kapoor, Goutomi Chatterjee, Neha Rastogi. Pediatric Hematology Oncology & BMT, Medanta The Medicity, Gurgaon, India
Financial Support: To provide free BMT, Airport Authority of India and Bina Refinery provided financial support through corporate social responsibility. Conditioning Regimen: Majority of patients (pts) received rATG-6mg/kg, FLU-150mg/m2, BU-12.8-16mg/kg (without PK studies) and cytoxan-200mg/kg. Prophylaxis; aGVHD: CSA/MTX. Acyclovir until day 100. Fluconazole until ANC >1000/mm3. Bactrim for PCP. G-CSF was not routinely administered. Follow-Up: Pts stayed in the hospital vicinity for up to 6 months post-BMT. The majority of outpatient medications were also provided free of charge. Results: Donors: 13F and 7M, median age 8 yrs (2-18). The median number of CD34+ cells harvested from bone marrow was 5.5 £ 106/kg (1.5-21.6); only 2 donors were G-CSF mobilized. Patients: First BMT was conducted in April 2018. Median FU 9 months (3-17). Of the first 20 pts, 12 were males. Pts were ages 2-5Y (n=9), 5-10Y (n=8) and >10Y (n=3). 19/20 pts were heavily transfused. Thalassemia spectrum (16/20), SCD (n=1), MDS (n=1), SAA (n=1), and CML (n=1). 4 pts with major ABO incompatibility underwent RBC desensitization. Median time for ALC >500/mm3, neutrophil and platelet engraftment was 19d (12 -30), 27d (14-33) and 25d (15-50), respectively. Two pts had graft failure (one died). At last follow up, two pts have stable mixed chimerism and 16 (80%) have donor chimerism >90%, all 18 engrafted pts are transfusion independent. Overall survival is 95%. The median cost of BMT was $11,000 ($6,000-22,000). Conclusion: Early results demonstrate the feasibility of our model. With appropriate remote supervision and dedicated general pediatricians and nurses with limited BMT training, we can successfully conduct MSD BMT in a resource-constrained set up. Despite living in remote villages, poverty, facing socio-cultural challenges, families can be trained to provide appropriate care at home. Multi-drug resistant bacteraemia and GI infections remain a major concern. Incidence Mucositis grade III-IV
0%
Bacteraemia
45%
CMV viremia
25%
ADV/ EBV viremia
0%
VZV reactivation
20%
Dengue
5%
Fungal infection
5%
GI parasitic infections
80%
Moderate-severe VOD
0%
PRES
0%
Grade II-IV aGVHD
5%
S217
322 Haematopoietic Stem Cell Transplant Outcomes in Patients with Thalassemia Major from a Tertiary Care Center in South India. Sunil Bhat1, Nataraj KS DM2, Shobha Badiger3, Annapandian Vmacademic research4, Sharat Damodar5. 1 Pediatric Hematology, Oncology and Bone marrow transplantation, Mazumdar Shaw Cancer Center, Narayana Health City, Bangalore, Bangalore, India; 2 Haematology, Mazumdar Shaw medical center, Bangalore, India; 3 Mazumdar Shaw Cancer Center, Narayana Health Center, Bangalore, Bangalore, India; 4 Narayana hrudayalaya foundations, Bangalore, India; 5 Department of Haematology, Mazumdar Shaw Cancer Center, Bengaluru, India Background: Hematopoietic stem cell transplant (HSCT) is widely used as a gene replacement therapy in Thalassemia patients for decades. Survival probabilities after HSCT have increased considerably with advancements in graft versus host disease (GVHD) preventive strategies and conditioning regimens. Here we report our HSCT experience in patients with Thalassemia major, with different graft sources, in terms of transplant outcomes such as neutrophil and platelet engraftment, acute and chronic graft versus host disease (GVHD), thalassemia free survival and overall survival. Methods: We analysed the data of 164 Thalassemia patients who have undergone HSCT between Jan-2012 to Jun-2019 at our centre. We evaluated the demographic and clinical characteristics of patients, graft source on the HSCT outcomes, such as engraftment, graft versus host disease, day-100 survival, thalassemia-free survival and overall survival. Results: Out of 164 patients, 100 (61%) were males, the mean age was 9.47§4.41 (range, 1 -24) years. Peripheral blood stem cell (50%) and bone marrow (47%) are the respective graft sources with predominant matched sibling donor transplants (60.4%). One third of the patients received Fludarabine/Busulfan/Cyclophosphamide based conditioning regimen. Twentyeight percent of the patients developed acute GVHD (grades IIV) and 7.3% developed chronic GVHD. The average time to neutrophil engraftment was 14 (range, 8-24) days and platelet engraftment was 18 (range, 8-72) days. The average time to neutrophil engraftment and platelets engraftment did not
Figure 1. Basic demographics and clinical details of the study patients based on HLA-donor type
S218
Abstracts / Biol Blood Marrow Transplant 26 (2020) S96 S255
significantly differ between the HLA-donor type (Figure 1). There were 26 deaths (15.9%) and 7 (4.3%) graft rejections during the follow-up. Infections are the major cause of deaths. The day 100 survival was 89%, the overall survival was 84% and the thalassemia free survival was 74.4%. Conclusion: HSCT with various preparative regimens, GVHD preventive strategies, and varied graft sources is certainly a unique curative option for the Thalassemia major patients in the developing world. The survival after HSCT in Thalassemia patients are similar regardless of stem cell source, donor-HLA type (Figure 2) and GVHD (Figure 3). However, the incidence of GVHD is more with matched unrelated donors.
Figure 2. Overall survival functions of Thalassemia patients after Haematopoietic stem cell transplantation based on HLA-match
Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH Introduction: We wanted to study the role of abatacept on the incidence of graft versus host disease (GVHD) in patients with sickle cell disease (SCD) undergoing allogeneic hematopoietic stem cell transplant (HSCT). Methods: We conducted a retrospective chart review of patients who received an allogeneic HSCT for SCD at Cincinnati Children’s Hospital Medical Center and compared various transplant characteristics between patients with and without abatacept for acute GVHD prophylaxis. Results: Sixteen patients were transplanted for SCD at our center. Nine patients received a calcineurin inhibitor, methotrexate and abatacept at 10 mg/kg intravenously on days -1, +5, +14 and +28 while 7 patients received a calcineurin inhibitor with methotrexate and methylprednisolone for acute GVHD prophylaxis (table 1). No abatacept infusion related adverse effects were observed. Neutrophil engraftment was comparable at a median of 12.5 days (range 11-21) in patients without abatacept versus 13 days (range 12-16 days) in the abatacept cohort. Incidence of grade 2-4 GVHD was 0/9 in the abatacept cohort versus 3/7 patients in the no-abatacept cohort. Two of the 3 acute GVHD patients in the no-abatacept cohort had visceral involvement. One patient in the abatacept cohort had mild chronic GVHD compared to 3 patients in the no-abatacept cohort with mild (n=1) and moderate (n=2) chronic GVHD. Six patients in the no-abatacept cohort had viral reactivation compared to 8/9 patients in the abatacept cohort. No patient in either cohort had viral disease. One patient in the abatacept cohort had secondary graft loss and was transplanted again with the same donor and conditioning regimen successfully. There was no graft loss in patients who did not receive abatacept. The disease-free survival was 100% in both groups at last follow up of 1925 days (range 837-8164 days) in the no-abatacept group and 770 days (range 112-1634 days) after HSCT in the abatacept cohort. Conclusions: Abatacept is well tolerated and decreases the incidence of acute and chronic GVHD in children with SCD undergoing fully matched sibling transplants. Larger studies are needed to definitively determine the impact of abatacept in GVHD prophylaxis in the matched sibling donor setting.
Table 1 Patient demographics
Figure 3. Effect of GVHD on overall survival functions of Thalassemia patients after Haematopoietic stem cell transplantation
323 Abatacept Decreases the Rate of Acute and Chronic Gvhd in Children with Sickle Cell Disease Undergoing Matched Sibling Transplants Ruby Khoury1, Michael S. Grimley MD2, Stella M. Davies MBBS, PhD3, Pooja Khandelwal MD1. 1 Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; 2 Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; 3 Division of
324 Haploidentical Stem Cell Transplant with Post-Transplant Cyclophosphamide with Busulfan, Fludarabine and Thiotepa Conditioning for Children with Thalassemia Major Satya Prakash Yadav MBBS, DCH, DNB, Anil Sharma, Rohit Kapoor, Goutomi Chatterjee, Neha Rastogi. Pediatric Hematology Oncology & BMT, Medanta The Medicity, Gurgaon, India