Single CBT As 2nd Allo-SCT Can be a Promising Therapeutic Strategy for Patients with Relapsed Hematopoietic Malignancies, Especially with Myeloid Neoplasms

Single CBT as 2nd allo-SCT can be a promising therapeutic strategy for patients with relapsed hematopoietic malignancies, especially with myeloid neoplasms.

Background: Second allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for hematopoietic malignancies that relapse after allo-SCT, but many patients do not receive 2nd allo-SCT at the best time because of the long preparation time for transplantation, and even if they do, treatment-related complications and relapse of the underlying disease often lead them to fatal outcomes. Umbilical cord blood (CB) is considered to be a promising source of 2nd allo-SCT because of its short preparation time, rapid and high graft-versus Leukemia (GVL) effect after transplantation, and better response to GVHD treatment compared to other donor sources. Therefore, we investigated the usefulness of cord blood transplantation (CBT) for relapsed hematopoietic malignancies after allo-SCT.

Methods: We retrospectively analyzed the outcomes of patients under 60 years old with hematopoietic malignancies who received single CBT (sCBT) as 2nd allo-SCT for relapse after allo-SCT in Toranomon Hospital between Apr. 1999 and Mar. 2022. We excluded the patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or higher.

Results: 154 patients were included in this study. There were 95 patients with myeloid neoplasms and 59 with lymphoid neoplasms. Median age was 41 years (range: 19-59). 133 patients were in non-remission and 21 in remission before SCT. Median interval between 1st SCT and 2nd SCT was 280.5 days (56-4703). Donor sources of 1st allo-SCT were related donor in 52, unrelated donor in 43, and single CB in 58 patients. 93 patients received myeloablative conditioning for 2nd allo-SCT, and 61 patients underwent reduced intensity-conditioning. Median observation period of survivors was 1526 (122-6286) days after 2nd allo-SCT. Overall survival (OS), non-relapse mortality (NRM) and relapse at 2-year were 23.5%, 36.6% and 46.0%, respectively. Patients with myeloid neoplasms had a significantly better prognosis than those with lymphoid neoplasms, with 2-year OS of 31.2% and 11.9%, respectively (P<0.01). Patients with longer interval between SCTs (≧1 year) had significantly better survival than those with shorter interval (<1 year), with 2-year OS of 34.8% and 15.9%, respectively (P<0.01). Donor sources of 1st allo-SCT had no significant impact on the prognosis of 2nd allo-SCT, but sCBT after related donors tended to have a better prognosis than sCBT after other donors, with 2-year OS of 34.8% and 17.8%, respectively (P=0.06).

The cumulative incidence of pre-engraftment immune reaction (PIR) was 61.0%, and that of severe form of PIR was 32.5%. Severe PIR resulted in significantly higher NRM (P=0.04).

The cumulative incidence of all grades of acute GVHD was 52.6%, and the cumulative incidence of grade 3 or higher acute GVHD was 17.0%.

In the multivariate analysis, myeloid neoplasms, younger age (≦40), long interval between SCTs(≧1 year) showed a superior OS. Poor prognostic factors were lymphoid neoplasms, severe form of PIR, older age (>40), short interval between SCTs(<1 year) for NRM; reduced intensity-conditioning and lymphoid neoplasms for relapse.

Conclusion: single CBT as 2nd allo-SCT may provide a favorable prognosis for patients with hematopoietic malignancies that have relapsed after allo-SCT, especially myeloid neoplasms. However, PIR should be managed with caution because severe PIR significantly increase NRM(P<0.01)

Yamamoto:Takeda Pharmaceutical Co.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Astellas Pharma Inc.: Honoraria; Asahi Kasei Pharma Co.: Honoraria; Sumitomo Pharma CO.,Ltd.: Honoraria; AstraZeneca: Honoraria; CSL Behring K.K: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; Novartis Pharma Co.: Honoraria; Janssen Pharmaceutical KK: Honoraria; JCR Pharmaceuticals Co.,Ltd.: Honoraria; MSD KK (Merck & Co.) Inc.: Honoraria. Yamaguchi:AbbVie GK.: Honoraria; Nippon Shinyaku Co.: Honoraria. Kaji:AbbVie GK.: Honoraria; Asahi Kasei Pharma Co.: Honoraria; AstraZeneca: Honoraria; Bristol Myers Squibb K.K.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Eisai Co.: Honoraria; Genmab: Honoraria; Janssen Pharmaceutical KK.: Honoraria; Meiji Seika Pharma Co.: Honoraria; Ono Pharmaceutical Co.: Honoraria; Pfizer Japan Inc.: Honoraria; Sanofi K.K.: Honoraria; SymBio Pharmaceuticals: Honoraria; Takeda Pharmaceutical Co.: Honoraria. Takagi:Okinaka Memorial Institute for Medical Research: Research Funding; The Japanese Society of Hematology: Research Funding; AbbVie GK.: Honoraria; Amgen KK.: Honoraria; Asahi Kasei Pharma Co.: Honoraria; Astellas Pharma Inc.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Daiichi Sankyo Co.: Honoraria; GlaxoSmithKline KK.: Honoraria; Janssen Pharmaceutical KK.: Honoraria; Kyowa Kirin Co.: Honoraria; MSD KK (Merck & Co. Inc.): Honoraria; Nippon Shinyaku Co.: Honoraria; Novartis Pharma Co.: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; Pfizer Japan Inc.: Honoraria; Sumitomo Pharma Co.: Honoraria; Takeda Pharmaceutical Co.: Honoraria. Yamamoto:AstraZeneca: Honoraria; Bristol Myers Squibb K.K.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Daiichi Sankyo Co.: Honoraria; Eisai Co.: Honoraria; Genmab: Honoraria; Janssen Pharmaceutical KK.: Honoraria; Meiji Seika Pharma Co.: Honoraria; Mundi Pharma Co.: Honoraria; Nihonkayaku Co.: Honoraria; Novartis Pharma Co.: Honoraria; Ono Pharmaceutical Co.: Honoraria; Pfizer Japan Inc.: Honoraria; Sanofi K.K.: Honoraria; Takeda Pharmaceutical Co.: Honoraria. Wake:AbbVie GK: Honoraria; Alexionpharma: Honoraria; Amgen KK: Honoraria; Asahi Kasei Pharma Co.: Honoraria; Astellas Pharma Inc.: Honoraria; AstraZeneca: Honoraria; Bristol Myers Squibb K.K: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Daiichi Sankyo Co.: Honoraria; Eisai Co.: Honoraria; GlaxoSmithKline KK.: Honoraria; Janssen Pharmaceutical KK.: Honoraria; Kyowa Kirin Co.: Honoraria; Meiji Seika Pharma Co.: Honoraria; Mundi Pharma Co.: Honoraria; Nihonkayaku Co.: Honoraria; Novartis Pharma Co.: Honoraria; Ono Pharmaceutical Co.: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; Pfizer Japan Inc.: Honoraria; Sanofi K.K.: Honoraria; SymBio Pharmaceuticals: Honoraria; Takeda Pharmaceutical Co.: Honoraria. Uchida:Asahi Kasei Pharma Co.: Honoraria; JCR Pharmaceuticals Co.: Research Funding; Nippon Boehringer Ingelheim Co.: Research Funding; Fuji Pharma Co.: Research Funding; Sumitomo Pharma Co.: Research Funding; Chugai Pharmaceutical Co.: Research Funding; CSL Behring: Honoraria; Takeda Pharmaceutical Co.: Consultancy; MSD (Merck & Co. Inc.): Honoraria; Astellas Pharma Inc.: Consultancy; Astellas Pharma Inc.: Honoraria; AstraZeneca: Honoraria; AbbVie GK: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; Kyowa Kirin Co.: Honoraria; SymBio Pharmaceuticals: Honoraria; Daiichi Sankyo Co.: Honoraria; Takeda Pharmaceutical Co.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Nippon Shinyaku Co.: Honoraria; Novartis Pharma Co.: Honoraria.