Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia
Refractory acute myeloid leukemia (AML), defined as failure of two cycles of induction therapy at diagnosis or of one cycle at relapse, represents a subgroup with poor outcomes. Haploidentical natural killer cell (NK) therapy is a strategy that is being explored in refractory malignancies. Historica...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-09-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897231198178 |
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| author | Uday Kulkarni Arun Kumar Arunachalam Hamenth Kumar Palani Reeshma Radhakrishnan Nair Nithya Balasundaram Arvind Venkatraman Anu Korula Sushil Selvarajan Sharon Lionel Poonkuzhali Balasubramanian Madhavi Maddali Aby Abraham Biju George Vikram Mathews |
| author_facet | Uday Kulkarni Arun Kumar Arunachalam Hamenth Kumar Palani Reeshma Radhakrishnan Nair Nithya Balasundaram Arvind Venkatraman Anu Korula Sushil Selvarajan Sharon Lionel Poonkuzhali Balasubramanian Madhavi Maddali Aby Abraham Biju George Vikram Mathews |
| author_sort | Uday Kulkarni |
| collection | DOAJ |
| description | Refractory acute myeloid leukemia (AML), defined as failure of two cycles of induction therapy at diagnosis or of one cycle at relapse, represents a subgroup with poor outcomes. Haploidentical natural killer cell (NK) therapy is a strategy that is being explored in refractory malignancies. Historically, at our center, patients with refractory AML have been treated with cytoreductive therapy (fludarabine + cytosine + granulocyte colony-stimulating factor ± idarubicin or mitoxantrone + etoposide) followed by 1-week rest and then reduced-intensity transplant with fludarabine + melphalan. We used the same backbone for this trial (CTRI/2019/02/017505) with the addition of CD56-positive cells from a family donor infused 1 day after the completion of chemotherapy. CD56-positive selection was done using a CliniMACS Prodigy system (Miltenyi Biotec, Bergisch Gladbach, Germany) followed by overnight incubation in autologous plasma with 2 micromolar arsenic trioxide and 500 U/mL of interleukin-2. From February 2019, 14 patients with a median age of 29 years (interquartile range [IQR]: 16.5–38.5) were enrolled in this trial. Six were females. Six had primary refractory AML while eight had relapsed refractory AML. The median CD56-cell dose infused was 46.16 × 106/kg (IQR: 25.06–70.36). One patient withdrew consent after NK cell infusion. Of the 13 patients who proceeded to transplant, five died of immediate post-transplant complications while two did not engraft but were in morphologic leukemia-free state (both subsequently died of infective complications after the second transplant). Of the remaining six patients who engrafted and survived beyond 1 month of the transplant, two developed disease relapse and died. The remaining four patients are alive and relapse free at the last follow-up (mean follow-up duration of surviving patients is 24 months). The 2-year estimated overall survival for the cohort was 28.6% ± 12.1% while the treatment-related mortality (TRM) with this approach was 38.5% ± 13.5%. Haploidentical NK cell therapy as an adjunct to transplant is safe and needs further exploration in patients with AML. For refractory AML, post-transplant NK infusion and strategies to reduce TRM while using pre-transplant NK infusion merit exploration. |
| first_indexed | 2024-03-12T00:46:30Z |
| format | Article |
| id | doaj.art-d4492367022c464e9341fd1d7b0aea08 |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-03-12T00:46:30Z |
| publishDate | 2023-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-d4492367022c464e9341fd1d7b0aea082023-09-14T17:03:30ZengSAGE PublishingCell Transplantation1555-38922023-09-013210.1177/09636897231198178Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid LeukemiaUday Kulkarni0Arun Kumar Arunachalam1Hamenth Kumar Palani2Reeshma Radhakrishnan Nair3Nithya Balasundaram4Arvind Venkatraman5Anu Korula6Sushil Selvarajan7Sharon Lionel8Poonkuzhali Balasubramanian9Madhavi Maddali10Aby Abraham11Biju George12Vikram Mathews13Department of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaDepartment of Haematology, Christian Medical College Vellore, Ranipet Campus, IndiaRefractory acute myeloid leukemia (AML), defined as failure of two cycles of induction therapy at diagnosis or of one cycle at relapse, represents a subgroup with poor outcomes. Haploidentical natural killer cell (NK) therapy is a strategy that is being explored in refractory malignancies. Historically, at our center, patients with refractory AML have been treated with cytoreductive therapy (fludarabine + cytosine + granulocyte colony-stimulating factor ± idarubicin or mitoxantrone + etoposide) followed by 1-week rest and then reduced-intensity transplant with fludarabine + melphalan. We used the same backbone for this trial (CTRI/2019/02/017505) with the addition of CD56-positive cells from a family donor infused 1 day after the completion of chemotherapy. CD56-positive selection was done using a CliniMACS Prodigy system (Miltenyi Biotec, Bergisch Gladbach, Germany) followed by overnight incubation in autologous plasma with 2 micromolar arsenic trioxide and 500 U/mL of interleukin-2. From February 2019, 14 patients with a median age of 29 years (interquartile range [IQR]: 16.5–38.5) were enrolled in this trial. Six were females. Six had primary refractory AML while eight had relapsed refractory AML. The median CD56-cell dose infused was 46.16 × 106/kg (IQR: 25.06–70.36). One patient withdrew consent after NK cell infusion. Of the 13 patients who proceeded to transplant, five died of immediate post-transplant complications while two did not engraft but were in morphologic leukemia-free state (both subsequently died of infective complications after the second transplant). Of the remaining six patients who engrafted and survived beyond 1 month of the transplant, two developed disease relapse and died. The remaining four patients are alive and relapse free at the last follow-up (mean follow-up duration of surviving patients is 24 months). The 2-year estimated overall survival for the cohort was 28.6% ± 12.1% while the treatment-related mortality (TRM) with this approach was 38.5% ± 13.5%. Haploidentical NK cell therapy as an adjunct to transplant is safe and needs further exploration in patients with AML. For refractory AML, post-transplant NK infusion and strategies to reduce TRM while using pre-transplant NK infusion merit exploration.https://doi.org/10.1177/09636897231198178 |
| spellingShingle | Uday Kulkarni Arun Kumar Arunachalam Hamenth Kumar Palani Reeshma Radhakrishnan Nair Nithya Balasundaram Arvind Venkatraman Anu Korula Sushil Selvarajan Sharon Lionel Poonkuzhali Balasubramanian Madhavi Maddali Aby Abraham Biju George Vikram Mathews Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia Cell Transplantation |
| title | Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia |
| title_full | Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia |
| title_fullStr | Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia |
| title_full_unstemmed | Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia |
| title_short | Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia |
| title_sort | haploidentical natural killer cell therapy as an adjunct to stem cell transplantation for treatment of refractory acute myeloid leukemia |
| url | https://doi.org/10.1177/09636897231198178 |
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