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1. Loss of CD34+ Cells and Effect of the Number of Viable Cryopreserved CD34+ Cells in the Infused Blood Grafts on Hematologic Recovery, Progression-Free Survival and Overall Survival in NHL Patients After Autologous Stem Cell Transplantation

Author

Partanen, Anu, Turunen, Antti, Valtola, Jaakko, Pyörälä, Marja, Kuittinen, Outi, Kuitunen, Hanne, Vasala, Kaija, Penttilä, Karri, Kuittinen, Taru, Mäntymaa, Pentti, Pelkonen, Jukka, Jantunen, Esa, and Varmavuo, Ville

Published
2023
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2. P409: BCL-2/BCL-XL INHIBITION INDUCES APOPTOSIS AND CIRCUMVENTS VENETOCLAX RESISTANCE IN TP53-MUTATED ACUTE MYELOID LEUKEMIA

Author

Vänttinen, Ida, primary, Kytölä, Sari, additional, Dufva, Olli, additional, Hellesøy, Monica, additional, Gullaksen, Stein-Erik, additional, Ruokoranta, Tanja, additional, Brück, Oscar, additional, Siitonen, Sanna, additional, Ettala, Pia, additional, Pyörälä, Marja, additional, Rimpilainen, Johanna, additional, Siitonen, Timo, additional, Tore Gjertsen, Bjorn, additional, Heckman, Caroline, additional, Kuusanmäki, Heikki, additional, and Kontro, Mika, additional

Published
2023
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3. P562: CAPILLARY BLOOD SAMPLING ALLOWS FEASIBLE METHOD FOR VENETOCLAX CONCENTRATION MEASUREMENT IN AN ACADEMIC MULTICENTER CLINICAL TRIAL CONTEXT

Author

Kytölä, Sari, primary, Vänttinen, Ida, additional, Kuusanmäki, Heikki, additional, Ruokoranta, Tanja, additional, Kurkela, Mika, additional, Kiiski, Johanna, additional, Holopainen, Annasofia, additional, Partanen, Anu, additional, Kuusisto, Milla E.L., additional, Koskela, Sirpa, additional, Räty, Riikka, additional, Itälä-Remes, Maija, additional, Ettala, Pia, additional, Rimpiläinen, Johanna, additional, Siitonen, Timo, additional, Pyörälä, Marja, additional, T. Backman, Janne, additional, Niemi, Mikko, additional, and Kontro, Mika, additional

Published
2023
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4. Loss of CD34+ Cells and Effect of the Number of Viable Cryopreserved CD34+ Cells in the Infused Blood Grafts on Hematologic Recovery, Progression-Free Survival and Overall Survival in NHL Patients After Autologous Stem Cell Transplantation

Author

Partanen, Anu, Turunen, Antti, Valtola, Jaakko, Pyörälä, Marja, Kuittinen, Outi, Kuitunen, Hanne, Vasala, Kaija, Penttilä, Karri, Kuittinen, Taru, Mäntymaa, Pentti, Pelkonen, Jukka, Jantunen, Esa, and Varmavuo, Ville

Published
2023
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5. Blood–Brain Barrier Disruption (BBBD)-Based Immunochemotherapy for Primary Central Nervous System Lymphoma (PCNSL), Early Results of a Phase II Study

Author

Kuitunen, Hanne K., primary, Rönkä, Aino L. K., additional, Sonkajärvi, Eila M., additional, Isokangas, Juha-Matti, additional, Pyörälä, Marja, additional, Palosaari, Kari A. A., additional, Jokimäki, Anna S., additional, Partanen, Anu E., additional, Littow, Harri J., additional, Vakkala, Merja A., additional, Jantunen, Esa J., additional, Huttunen, Mirja E., additional, Marin, Katja J., additional, Aromaa-Häyhä, Annikki M. K., additional, Auvinen, Päivi K., additional, Selander, Tuomas, additional, Puhakka, Inka K., additional, and Kuittinen, Outi M., additional

Published
2023
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6. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia

Author

Kuusanmäki, Heikki, primary, Kytölä, Sari, additional, Vänttinen, Ida, additional, Ruokoranta, Tanja, additional, Ranta, Amanda, additional, Huuhtanen, Jani, additional, Suvela, Minna, additional, Parsons, Alun, additional, Holopainen, Annasofia, additional, Partanen, Anu, additional, Kuusisto, Milla E.L., additional, Koskela, Sirpa, additional, Räty, Riikka, additional, Itälä-Remes, Maija, additional, Västrik, Imre, additional, Dufva, Olli, additional, Siitonen, Sanna, additional, Porkka, Kimmo, additional, Wennerberg, Krister, additional, Heckman, Caroline A., additional, Ettala, Pia, additional, Pyörälä, Marja, additional, Rimpiläinen, Johanna, additional, Siitonen, Timo, additional, and Kontro, Mika, additional

Published
2022
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7. Ex Vivo Venetoclax Sensitivity Testing Predicts Response and Overall Survival in De Novo and s/R/R AML Patients Treated with Azacitidine and Venetoclax

Author

Kytölä, Sari, primary, Vänttinen, Ida, additional, Ruokoranta, Tanja, additional, Holopainen, Annasofia, additional, Partanen, Anu, additional, Kuusisto, Milla E.L., additional, Koskela, Sirpa, additional, Räty, Riikka, additional, Itälä-Remes, Maija, additional, Ranta, Amanda, additional, Suvela, Minna, additional, Parsons, Alun, additional, Västrik, Imre, additional, Siitonen, Sanna M., additional, Porkka, Kimmo, additional, Wennerberg, Krister, additional, Heckman, Caroline A., additional, Ettala, Pia, additional, Rimpiläinen, Johanna, additional, Siitonen, Timo, additional, Pyörälä, Marja, additional, Kuusanmäki, Heikki, additional, and Kontro, Mika, additional

Published
2022
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8. Impact of the number of cryopreserved CD34+ cells in the infused blood grafts on hematologic recovery and survival in myeloma patients after autologous stem cell transplantation: Experience from the GOA study

Author

Partanen, Anu, primary, Turunen, Antti, additional, Silvennoinen, Raija, additional, Valtola, Jaakko, additional, Pyörälä, Marja, additional, Siitonen, Timo, additional, Sikiö, Anu, additional, Putkonen, Mervi, additional, Sankelo, Marja, additional, Penttilä, Karri, additional, Kuittinen, Taru, additional, Mäntymaa, Pentti, additional, Pelkonen, Jukka, additional, Jantunen, Esa, additional, and Varmavuo, Ville, additional

Published
2022
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9. Comparison of <scp>CD34</scp> + cell mobilization, blood graft cellular composition, and post‐transplant outcome in myeloma patients mobilized with filgrastim or pegfilgrastim added to low‐dose cyclophosphamide: A prospective multicenter study

Author

Kuittinen Taru, Mäntymaa Pentti, Siitonen Timo, Penttilä Karri, Pelkonen Jukka, Putkonen Mervi, Valtola Jaakko, Varmavuo Ville, Turunen Antti, Silvennoinen Raija, Sankelo Marja, Pyörälä Marja, Partanen Anu, Jantunen Esa, and Sikiö Anu

Subjects
medicine.medical_specialty, Cyclophosphamide, biology, Bortezomib, business.industry, Immunology, Urology, Hematology, Filgrastim, medicine.disease, CD19, 03 medical and health sciences, 0302 clinical medicine, Apheresis, 030220 oncology & carcinogenesis, PEG ratio, medicine, biology.protein, Immunology and Allergy, business, Pegfilgrastim, Multiple myeloma, 030215 immunology, medicine.drug
Abstract

Background Scarce data exist on the impact of granulocyte-colony stimulating factor (G-CSF) type on the mobilizing capacity of CD34+ cells, graft cellular composition, and outcome in myeloma (MM) patients. Patients and methods In this prospective multicenter study, 70 patients with MM received filgrastim (FIL) and 20 patients received pegfilgrastim (PEG) as a G-CSF after low-dose cyclophosphamide. Flow cytometry was used to analyze the mobilization of CD34+ cells and cellular composition of blood grafts, hematologic recovery, and survival after auto-SCT according to the G-CSF choice. Results The CD34+ cell yield of the first apheresis was higher in the FIL group (5.3 vs. 4.2 × 106 /kg, p = .025). The better mobilizing capacity was observed in the FIL group especially after bortezomib-based induction based on the higher first apheresis yield of CD34+ cells (7.5 vs. 4.4 × 106 /kg, p = .001). The median CD19+ cell count (1.0 vs. 0.4 × 106 /kg, p = .010) and the number of CD3+ T lymphocytes (43.1 vs. 31.8 × 106 /kg, p = .122) in the infused graft were higher in the patients mobilized with FIL. Both early (day +15) (56 vs. 108 × 109 /L, p = .002) and later platelet recovery at 6 months (191 vs. 226 × 109 /L, p = .026) were faster in the PEG group. Conclusion G-CSF type seems to impact on the mobilization capacity and cellular composition of infused graft and also platelet recovery post-transplant. A randomized study might be warranted to verify the effects of G-CSF choice in the mobilization field.

Published
2021

10. Copy number alterations define outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia

Author

Hohtari, Helena, Pallisgaard, Niels, Kankainen, Matti, Ellonen, Pekka, Brück, Oscar, Siitonen, Timo, Säily, Marjaana, Sinisalo, Marjatta, Pyörälä, Marja, Itälä-Remes, Maija, Koskenvesa, Perttu, Elonen, Erkki, Mustjoki, Satu, Porkka, Kimmo, TRIMM - Translational Immunology Research Program, University of Helsinki, HUSLAB, HUS Helsinki and Uusimaa Hospital District, Department of Medical and Clinical Genetics, Digital Precision Cancer Medicine (iCAN), HUS Diagnostic Center, Institute for Molecular Medicine Finland, Faculty Common Matters (Faculty of Medicine), HUS Comprehensive Cancer Center, Helsinki University Hospital Area, Department of Oncology, Hematologian yksikkö, Department of Clinical Chemistry and Hematology, and Clinicum

Subjects
3122 Cancers, 3111 Biomedicine
Abstract

Funding Information: NGS library preparation, sequencing and sequence analysis were performed by the Institute for Molecular Medicine Finland (FIMM) Technology Center, University of Helsinki. We thank laboratory technicians Jay Klievink in Hematology Research Unit Helsinki (HRUH) and Minna Suvela in FIMM for technical support with the DNA extractions and laboratory coordinator Minna Tuominen in FIMM for technical support with multiplex ligation-dependent probe amplification. We are grateful to the members of the HRUH for discussions and technical help. We thank research nurses Anne Gesterberg, Jenni Raali and Susanna Helkkula for help with clinical data. We thank Dr Veli Kairisto in Tykslab, Dr Taru Kuittinen in Kuopio University Hospital and clinical laboratory geneticists Anne Juvonen and Tarja Salonen in HUSLAB for help with clinical samples. The samples of this project were provided by Finnish University Hospital clinical laboratories and the Finnish Hematology Registry and Clinical Biobank (FHRB) with appropriate ethics approval (Dnro 202/06.01.00/2013). We thank all the patients for their generous participation. The FHRB Biobank is supported by the Finnish Association of Hematology, the Finnish Red Cross Blood Service, Institute for Molecular Medicine Finland, and the participating hospitals in Finland. This study was supported by the Doctoral Program in Clinical Research at the University of Helsinki and personal grants (to HH) from Emil Aaltonen Foundation, Ida Montin Foundation, Blood Disease Research Foundation, Finnish Hematology Association, Finnish Medical Foundation, Biomedicum Helsinki Foundation, Paulo Foundation, (to SM) Finnish Cancer Organizations, Sigrid Juselius Foundation, Signe and Ane Gyllenberg Foundation, Relander Foundation, and state funding for university-level health research in Finland. The laboratory analytics costs of this study were funded by Incyte. Funding Information: TS (not related to this study) is a member of the advisory board of Celgene and AbbVie; is a member of the advisory board of and received lecture fees from Pfizer and Janssen-Cilag; received lecture fees from Bristol Myers Squibb; received congress fees from and is a member of the advisory board of Novartis; received congress fees from Amgen. MP (not-related to this study) is a member of the advisory board of Pfizer and AbbVie; received lecture and congress fees from Novartis. OB received consultancy fees from Novartis and Sanofi. SM (not related to this study) received research funding from Novartis, BMS, Janpix, and Pfizer. All other authors have no conflicts of interest to disclose. Funding Information: NGS library preparation, sequencing and sequence analysis were performed by the Institute for Molecular Medicine Finland (FIMM) Technology Center, University of Helsinki. We thank laboratory technicians Jay Klievink in Hematology Research Unit Helsinki (HRUH) and Minna Suvela in FIMM for technical support with the DNA extractions and laboratory coordinator Minna Tuominen in FIMM for technical support with multiplex ligation-dependent probe amplification. We are grateful to the members of the HRUH for discussions and technical help. We thank research nurses Anne Gesterberg, Jenni Raali and Susanna Helkkula for help with clinical data. We thank Dr Veli Kairisto in Tykslab, Dr Taru Kuittinen in Kuopio University Hospital and clinical laboratory geneticists Anne Juvonen and Tarja Salonen in HUSLAB for help with clinical samples. The samples of this project were provided by Finnish University Hospital clinical laboratories and the Finnish Hematology Registry and Clinical Biobank (FHRB) with appropriate ethics approval (Dnro 202/06.01.00/2013). We thank all the patients for their generous participation. The FHRB Biobank is supported by the Finnish Association of Hematology, the Finnish Red Cross Blood Service, Institute for Molecular Medicine Finland, and the participating hospitals in Finland. Non

Published
2022

11. Efficacy of conventional-dose cytarabine, idarubicin and thioguanine versus intermediate-dose cytarabine and idarubicin in the induction treatment of acute myeloid leukemia: Long-term results of the prospective randomized nationwide AML-2003 study by the Finnish Leukemia Group

Author

Kolonen, Aarne, Sinisalo, Marjatta, Huhtala, Heini, Rimpiläinen, Johanna, Rintala, Hannele, Sankelo, Marja, Koivunen, Elli, Silvennoinen, Raija, Räty, Riikka, Ruutu, Tapani, Volin, Liisa, Porkka, Kimmo, Jantunen, Esa, Nousiainen, Tapio, Kuittinen, Taru, Penttilä, Karri, Pyörälä, Marja, Säily, Marjaana, Koistinen, Pirjo, Kauppila, Marjut, Itälä-Remes, Maija, Ollikainen, Hanna, Rauhala, Auvo, Kairisto, Veli, Pelliniemi, Tarja Terttu, Elonen, Erkki, Tampere University, Department of Internal medicine, Clinical Medicine, Health Sciences, and Department of Clinical Chemistry

Subjects
Leukemia, Myeloid, Acute, Neoplasm, Residual, Antineoplastic Combined Chemotherapy Protocols, Remission Induction, Cytarabine, Humans, Prospective Studies, Middle Aged, 3121 Internal medicine, Idarubicin, Thioguanine, Finland
Abstract

Objectives: AML-2003 study sought to compare the long-term efficacy and safety of IAT and IdAraC-Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy. Methods: Patients were randomized to receive either IAT or IdAraC-Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification. Structured questionnaire forms were used to gather data prospectively. Results: A total of 356 AML patients with a median age of 53 years participated in the study. Long-term overall survival (OS) and relapse-free survival (RFS) were both 49% at 10 years. The median follow-up was 114 months. No significant difference in remission rate, OS or RFS was observed between the two induction treatments. Risk classification according to the protocol, MRD after the first and the last consolidation treatment affected the OS and RFS significantly (p

Published
2022

12. Copy number alterations define outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia

Author

Hohtari, Helena, primary, Pallisgaard, Niels, additional, Kankainen, Matti, additional, Ellonen, Pekka, additional, Brück, Oscar, additional, Siitonen, Timo, additional, Säily, Marjaana, additional, Sinisalo, Marjatta, additional, Pyörälä, Marja, additional, Itälä-Remes, Maija, additional, Koskenvesa, Perttu, additional, Elonen, Erkki, additional, Mustjoki, Satu, additional, and Porkka, Kimmo, additional

Published
2022
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13. Impact of the number of cryopreserved CD34+ cells in the infused blood grafts on hematologic recovery and survival in myeloma patients after autologous stem cell transplantation: Experience from the GOA study.

Author

Partanen, Anu, Turunen, Antti, Silvennoinen, Raija, Valtola, Jaakko, Pyörälä, Marja, Siitonen, Timo, Sikiö, Anu, Putkonen, Mervi, Sankelo, Marja, Penttilä, Karri, Kuittinen, Taru, Mäntymaa, Pentti, Pelkonen, Jukka, Jantunen, Esa, and Varmavuo, Ville

Subjects
STEM cell transplantation, OVERALL survival, CRYOPRESERVATION of cells, PROGRESSION-free survival, BLOOD cells
Abstract

Background: Prospective data on the impact of CD34+ cell loss during cryopreservation and the amount of cryopreserved CD34+ cells infused after high‐dose therapy on hematologic recovery and post‐transplant outcome in multiple myeloma (MM) are scarce. Patients and methods: This post‐hoc study aimed to investigate factors associating with CD34+ cell loss during cryopreservation and the effects of the infusion of a very low number (<1.0 × 106/kg, group A), low number (1–1.9 × 106/kg, group B), and optimal number (≥2 × 106/kg, group C) of thawed viable CD34+ cells on hematologic recovery, progression free survival, and overall survival after autologous stem cell transplantation among 127 patients with MM. Results: In group C, pegfilgrastim use (P = 0.001), plerixafor use (P = 0.039), and older age ≥ 60 years (P = 0.026) were associated with less loss of CD34+ cells during cryopreservation. Better mobilization efficacy correlated with greater CD34+ cell loss in group B (P = 0.013 and P = 0.001) and in group C (P < 0.001 and P < 0.001). Early platelet engraftment was slowest in group A (20 d vs 12 d in group B vs 11 d in group C, P = 0.003). The infused viable CD34+ cell count <1.0 × 106/kg seemed not to have influence on PFS (P = 0.322) or OS (P = 0.378) in MM patients. Conclusions: Cryopreservation impacts significantly on the CD34+ cell loss. A very low number of graft viable CD34+ cells did not affect PFS or OS. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Ex Vivo Drug Sensitivity Testing to Predict Response to Venetoclax + Azacitidine in Acute Myeloid Leukemia: Interim Results of the Prospective Multicenter Phase II Venex Trial

Author

Kuusanmäki, Heikki, primary, Kytölä, Sari, additional, Vänttinen, Ida, additional, Ranta, Amanda, additional, Ruokoranta, Tanja, additional, Holopainen, Annasofia, additional, Koskela, Sirpa, additional, Kuusisto, Milla E.L., additional, Porkka, Kimmo, additional, Räty, Riikka, additional, Västrik, Imre, additional, Wennerberg, Krister, additional, Heckman, Caroline A., additional, Ettala, Pia, additional, Pyörälä, Marja, additional, Rimpiläinen, Johanna, additional, Siitonen, Timo, additional, and Kontro, Mika, additional

Published
2021
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16. Autograft cellular composition and outcome in myeloma patients: Results of the prospective multicenter GOA study

Author

Turunen, Antti, primary, Silvennoinen, Raija, additional, Partanen, Anu, additional, Valtola, Jaakko, additional, Siitonen, Timo, additional, Putkonen, Mervi, additional, Sankelo, Marja, additional, Pyörälä, Marja, additional, Kuittinen, Taru, additional, Penttilä, Karri, additional, Sikiö, Anu, additional, Savolainen, Eeva‐Riitta, additional, Mäntymaa, Pentti, additional, Pelkonen, Jukka, additional, Varmavuo, Ville, additional, and Jantunen, Esa, additional

Published
2021
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17. Pleriksafori kantasolujen mobilisaatiossa autologista siirtoa varten

Author

Jantunen, Esa, Valtola, Jaakko, Partanen, Anu, Turunen, Antti, Kuittinen, Taru, Silvennoinen, Raija, Pyörälä, Marja, Mäntymaa, Pentti, Pelkonen, Jukka, Varmavuo, Ville, HUS Pää- ja kaulakeskus, Syöpätautien osasto, Hematologian yksikkö, HYKS erva, and Kymsote - Kymenlaakson sosiaali- ja terveyspalvelujen kuntayhtymä

Subjects
Lymphoma, 3122 Syöpätaudit, Heterocyclic Compounds, +therapy, Autografts, Multiple Myeloma, Prognosis, Transplantation, Autologous, Hematopoietic Stem Cell Mobilization, Stem Cell Transplantation
Abstract

Vertaisarvioitu. English summary Autologisella kantasolusiirrolla tuetulla intensiivihoidolla on keskeinen rooli etenkin multippelia myeloomaa sekä tietyissä tilanteissa lymfoomaa sairastavien potilaiden hoidossa. Huono tai epäonnistunut kantasolujen mobilisaatio ja keräys on tärkeä autologisen kantasolusiirron saatavuutta rajoittava tekijä. Noin vuosikymmenen ajan käytössä olleella pleriksaforilla voidaan usein auttaa potilaita, joiden kantasolut mobilisoituvat huonosti vaikuttamatta siirronjälkeiseen ennusteeseen. Pleriksaforin käytön on todettu vaikuttavan kerättyjen kantasolusiirteiden solukoostumukseen sekä potilaiden siirronjälkeiseen hematologiseen ja immunologiseen toipumiseen. Näiden löydösten kliininen merkitys vaatii vielä lisäselvityksiä, kuten optimaalisen autologisen kantasolusiirteen koostumuskin. Pleriksaforin optimaalisen ja etenkin kustannustehokkaan käytön kannalta on keskeistä tunnistaa oikeat potilasryhmät esimerkiksi tutkimuksissa varmennetuin algoritmein.

Published
2020

18. Mobilization characteristics, blood graft composition, and outcome in diffuse large B‐cell lymphoma after autologous stem cell transplantation: Results from the prospective multicenter GOA study

Author

Partanen, Anu, primary, Turunen, Antti, additional, Valtola, Jaakko, additional, Pyörälä, Marja, additional, Vasala, Kaija, additional, Kuittinen, Outi, additional, Kuitunen, Hanne, additional, Penttilä, Karri, additional, Keskinen, Leena, additional, Kuittinen, Taru, additional, Mäntymaa, Pentti, additional, Pelkonen, Jukka, additional, Varmavuo, Ville, additional, and Jantunen, Esa, additional

Published
2020
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21. Autologous stem cell transplantation in peripheral T-cell lymphoma: better mobilization of blood CD34+ cells is associated with improved survival

Author

Partanen, Anu, primary, Turunen, Antti, additional, Valtola, Jaakko, additional, Pyörälä, Marja, additional, Vasala, Kaija, additional, Kuittinen, Outi, additional, Kuitunen, Hanne, additional, Penttilä, Karri, additional, Kuittinen, Taru, additional, Mäntymaa, Pentti, additional, Pelkonen, Jukka, additional, Varmavuo, Ville, additional, and Jantunen, Esa, additional

Published
2020
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22. Autograft cellular composition and outcome in NHL patients: results of the prospective multicenter GOA study

Author

Turunen, Antti, primary, Valtola, Jaakko, additional, Partanen, Anu, additional, Ropponen, Antti, additional, Kuittinen, Outi, additional, Kuitunen, Hanne, additional, Vasala, Kaija, additional, Ågren, Lasse, additional, Penttilä, Karri, additional, Keskinen, Leena, additional, Savolainen, Eeva-Riitta, additional, Pyörälä, Marja, additional, Kuittinen, Taru, additional, Selander, Tuomas, additional, Mäntymaa, Pentti, additional, Pelkonen, Jukka, additional, Jantunen, Esa, additional, and Varmavuo, Ville, additional

Published
2020
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23. CD34+ cell mobilization, blood graft composition, and posttransplant recovery in myeloma patients compared to non‐Hodgkinʼs lymphoma patients: results of the prospective multicenter GOA study

Author

Turunen, Antti, primary, Partanen, Anu, additional, Valtola, Jaakko, additional, Ropponen, Antti, additional, Siitonen, Timo, additional, Kuittinen, Outi, additional, Kuitunen, Hanne, additional, Putkonen, Mervi, additional, Sankelo, Marja, additional, Keskinen, Leena, additional, Savolainen, Eeva‐Riitta, additional, Pyörälä, Marja, additional, Kuittinen, Taru, additional, Silvennoinen, Raija, additional, Penttilä, Karri, additional, Sikiö, Anu, additional, Vasala, Kaija, additional, Mäntymaa, Pentti, additional, Pelkonen, Jukka, additional, Varmavuo, Ville, additional, and Jantunen, Esa, additional

Published
2020
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24. A prospective comparison of pegfilgrastim and lipegfilgrastim combined with chemotherapy in the mobilization of CD34 + cells in NHL patients

Author

Partanen, Anu, primary, Turunen, Antti, additional, Valtola, Jaakko, additional, Vasala, Kaija, additional, Ågren, Lasse, additional, Penttilä, Karri, additional, Pyörälä, Marja, additional, Kuittinen, Taru, additional, Mäntymaa, Pentti, additional, Pelkonen, Jukka, additional, Jantunen, Esa, additional, and Varmavuo, Ville, additional

Published
2020
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25. ERCC6L2 defines a novel entity within inherited acute myeloid leukemia

Author

Douglas, Suvi P. M., Siipola, Pihla, Kovanen, Panu E., Pyörälä, Marja, Kakko, Sakari, Savolainen, Eeva-Riitta, Salmenniemi, Urpu, Orte, Katri, Kytölä, Soili, Pitkänen, Esa, Porkka, Kimmo, Kilpivaara, Outi, Wartiovaara-Kautto, Ulla, ATG - Applied Tumor Genomics, Research Programs Unit, Faculty of Medicine, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, HUSLAB, Clinicum, HUS Comprehensive Cancer Center, University Management, Department of Medicine, Hematologian yksikkö, Department of Oncology, and Staff Services

Subjects
MUTATIONS, education, 3122 Cancers, DNA-REPAIR, BONE-MARROW-FAILURE, NEOPLASMS
Published
2019

27. ERCC6L2 defines a novel entity within inherited acute myeloid leukemia

Author

Douglas, Suvi P. M., primary, Siipola, Pihla, additional, Kovanen, Panu E., additional, Pyörälä, Marja, additional, Kakko, Sakari, additional, Savolainen, Eeva-Riitta, additional, Salmenniemi, Urpu, additional, Orte, Katri, additional, Kytölä, Soili, additional, Pitkänen, Esa, additional, Porkka, Kimmo, additional, Kilpivaara, Outi, additional, and Wartiovaara-Kautto, Ulla, additional

Published
2019
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28. Mobilization characteristics, blood graft composition, and outcome in diffuse large B‐cell lymphoma after autologous stem cell transplantation: Results from the prospective multicenter GOA study.

Author

Partanen, Anu, Turunen, Antti, Valtola, Jaakko, Pyörälä, Marja, Vasala, Kaija, Kuittinen, Outi, Kuitunen, Hanne, Penttilä, Karri, Keskinen, Leena, Kuittinen, Taru, Mäntymaa, Pentti, Pelkonen, Jukka, Varmavuo, Ville, and Jantunen, Esa

Subjects
STEM cell transplantation, DIFFUSE large B-cell lymphomas, BLOOD cell count, LYMPHOMAS, PROGRESSION-free survival, BLOOD
Abstract

Background: Diffuse large B‐cell lymphoma (DLBCL) is a common indication for autologous stem cell transplantation (auto‐SCT). Study Design and Methods: This prospective noninterventional study aimed to evaluate the impact of mobilization characteristics and graft cellular content on hematologic recovery and outcome after auto‐SCT among 68 patients with DLBCL. Results: Better mobilization capacity as manifested by blood CD34+ cell count >32 × 106/L and CD34+ cell yield of the first apheresis >2.75 × 106/kg correlated with faster neutrophil (P =.005 and P =.017) and platelet (P =.002 and P <.001) recovery. A higher number of infused CD34+ cells (> 2.65 × 106/kg) was associated with better 5‐year overall survival (OS; 95% vs 67%, P =.012). The graft CD34+CD133+CD38− cell count >0.07 × 106/kg was predictive of better 5‐year OS (87% vs 63%; P =.008) and higher graft CD3+ cell count (>23.1 × 106/kg) correlated also with better 5‐year OS (80% vs 40%, P =.008). In multivariate analysis only disease status of CR I at auto‐SCT was associated with better progression‐free survival (P =.014) and OS (P =.039). Conclusion: The mobilization capacity of CD34+ cells impacted on early hematologic recovery in patients with DLBCL after auto‐SCT. Higher graft CD34+ cell count and both CD34+CD133+CD38− and CD3+ cells were also associated with better OS. The effect of optimal graft cellular composition on outcome in DLBCL should be evaluated in a randomized study. [ABSTRACT FROM AUTHOR]

Published
2021
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29. A prospective comparison of pegfilgrastim and lipegfilgrastim combined with chemotherapy in the mobilization of CD34+ cells in NHL patients.

Author

Partanen, Anu, Turunen, Antti, Valtola, Jaakko, Vasala, Kaija, Ågren, Lasse, Penttilä, Karri, Pyörälä, Marja, Kuittinen, Taru, Mäntymaa, Pentti, Pelkonen, Jukka, Jantunen, Esa, and Varmavuo, Ville

Subjects
GRANULOCYTE-colony stimulating factor, STEM cell transplantation, BLOOD cells, CANCER chemotherapy
Abstract

Background: Autologous stem cell transplantation (auto‐SCT) is a treatment approach in non‐Hodgkin lymphoma (NHL) patients. The options for mobilization of CD34+ cells to support high‐dose therapy are granulocyte‐colony stimulating factors (G‐CSFs) alone or after chemotherapy. Limited data exist on the efficacy of lipegfilgrastim (LIPEG) in the mobilization field. Patients and Methods: The present prospective nonrandomized study compared LIPEG 6 mg (n = 40) with pegfilgrastim (PEG) 6 mg (n = 37) in the mobilization of blood CD34+ cells after chemotherapy in NHL patients with comparable mobilizing chemotherapy and disease status before auto‐SCT. Results: Significantly higher blood CD34+ cell (B‐CD34+) counts were observed in the LIPEG group at the start of the first apheresis (44 vs 23 × 106/L, P =.009), in line with a higher collection yield of the first apheresis (3.3 vs 2.1 × 106/kg, P =.086) and total yield of CD34+ cells (4.7 vs 2.9 × 106/kg, P =.004). LIPEG proved to be a more effective G‐CSF, resulting in a higher B‐CD34+ cell peak (60 vs 32 × 106/L, P =.030) and higher proportion of excellent mobilizers (33% vs 8%, P =.008). The superiority of LIPEG was confirmed in the multivarite analysis concerning the CD34+ cell yield of the first apheresis day (P =.010) and the total yield (P =.001). Conclusion: The mobilization of blood grafts with LIPEG added to chemotherapy was associated with higher CD34+ cell apheresis yields than with PEG. A randomized study is warranted to verify these findings. [ABSTRACT FROM AUTHOR]

Published
2020
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30. Blood graft composition and post-transplant recovery in myeloma patients mobilized with plerixafor: a prospective multicenter study

Author

Valtola, Jaakko, primary, Silvennoinen, Raija, additional, Ropponen, Antti, additional, Siitonen, Timo, additional, Säily, Marjaana, additional, Sankelo, Marja, additional, Putkonen, Mervi, additional, Partanen, Anu, additional, Pyörälä, Marja, additional, Savolainen, Eeva-Riitta, additional, Mäntymaa, Pentti, additional, Pelkonen, Jukka, additional, Jantunen, Esa, additional, and Varmavuo, Ville, additional

Published
2018
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31. Old enemies in new disguises: emergence ofEnterococcus faeciumas a significant clinical problem at an adult haematology ward

Author

Hämäläinen, Sari, primary, Pentikäinen, Jaana, additional, Reijula, Jori, additional, Mauranen, Ella, additional, Koivula, Irma, additional, Lindholm, Laura, additional, Juutilainen, Auni, additional, Nousiainen, Tapio, additional, Pyörälä, Marja, additional, Vuopio, Jaana, additional, and Jantunen, Esa, additional

Published
2017
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32. Blood graft composition and post-transplant recovery in myeloma patients mobilized with plerixafor: a prospective multicenter study.

Author

Valtola, Jaakko, Partanen, Anu, Pyörälä, Marja, Silvennoinen, Raija, Jantunen, Esa, Varmavuo, Ville, Ropponen, Antti, Pelkonen, Jukka, Siitonen, Timo, Säily, Marjaana, Sankelo, Marja, Putkonen, Mervi, Savolainen, Eeva-Riitta, and Mäntymaa, Pentti

Subjects
KILLER cells, B cells, T cells, LONGITUDINAL method, BLOOD
Abstract

The composition of autologous blood grafts after cryopreservation, post-transplant hematological recovery up to 1 year and immune recovery up to 6 months as well as outcome was analyzed in 87 patients with multiple myeloma (MM). The patients receiving added plerixafor due to poor mobilization (11%) were compared to those mobilized with G-CSF or cyclophosphamide (CY) plus G-CSF. The use of plerixafor was found to significantly affect the graft composition as there was a significantly higher proportion of the more primitive CD34+ cells, higher number of T and B lymphocytes as well as NK cells in the grafts of patients who received also plerixafor. The hematological recovery after auto-SCT was comparable between the groups. The recovery of CD3+CD4+ T cells was faster in plerixafor mobilized patients at 1 and 3 months post-transplant. There were no significant differences in progression-free (PFS) or overall survival (OS) according to the plerixafor use. [ABSTRACT FROM AUTHOR]

Published
2019
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33. Autologous stem cell transplantation in peripheral T-cell lymphoma: better mobilization of blood CD34+ cells is associated with improved survival.

Author

Partanen, Anu, Turunen, Antti, Valtola, Jaakko, Pyörälä, Marja, Vasala, Kaija, Kuittinen, Outi, Kuitunen, Hanne, Penttilä, Karri, Kuittinen, Taru, Mäntymaa, Pentti, Pelkonen, Jukka, Varmavuo, Ville, and Jantunen, Esa

Subjects
LEUKAPHERESIS, STEM cell transplantation, T-cell lymphoma, BLOOD cells, GRANULOCYTE-colony stimulating factor
Abstract

The disease status at the time point of auto-SCT was CR1 in the majority of the patients (17 patients; 68%) and only one patient had experienced a relapse before auto-SCT. In addition, one patient with an apheresis yield of 1.8 × 10 SP 6 sp /kg CD34 SP + sp cells and another with a yield of 1.9 × 10 SP 6 sp /kg CD34 SP + sp cells were accepted to proceed to auto-SCT. Overall survival of the 25 patients with peripheral T-cell lymphoma according to yield of CD34+ cells of the first apheresis. [Extracted from the article]

Published
2020
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35. Targeting Venetoclax Resistance in TP53-Mutated Acute Myeloid Leukemia

Author

Vänttinen, Ida, Ruokoranta, Tanja, Saad, Joseph J, Kytölä, Sari, Hellesøy, Monica, Gullaksen, Stein-Erik, Ettala, Pia-Sofia, Pyörälä, Marja, Rimpiläinen, Johanna, Siitonen, Timo, Wennerberg, Krister, Gjertsen, Bjorn T., Heckman, Caroline A., Kontro, Mika, and Kuusanmäki, Heikki

Abstract

Introduction: The combination therapy of Venetoclax (Ven) and Azacitidine (Aza) has shown remarkable improvements in the treatment of acute myeloid leukemia (AML) patients not eligible for chemotherapy. Nevertheless, patients with TP53-mutated AML are more prone to have a refractory disease or develop rapid resistance. A recent study indicated that a combined expression ratio of BCL-2, BCL-XL and MCL-1 proteins in leukemic stem cells predicts clinical response to Ven+Aza (Waclawiczek et al. 2023). Furthermore, our previous work has demonstrated that erythroid and megakaryoblastic leukemia blasts are more dependent on BCL-XL than BCL-2 (Kuusanmäki et al. 2023). Emerging evidence suggests that the erythroid-biased differentiation and gene signature is enhanced in many TP53-mutated patients (Rodriquez-Meira et al. 2022). Here we hypothesized that in TP53 -mutated AML, leukemic blasts correspond more closely to megakaryocyte-erythroid progenitors (MEPs) leading to an unfavorable BCL-2 family expression ratio, which can be associated with poor responses to Ven. Consequently, we aimed to identify novel compounds targeting this specific patient subgroup.

Published
2023
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37. Stem Cell Graft Cellular Composition, Hematological and Immune Recovery in NHL Patients Mobilized with or without Plerixafor: A Prospective Comparison

Author

Valtola, Jaakko, primary, Varmavuo, Ville, additional, Ropponen, Antti, additional, Pyörälä, Marja, additional, Nihtinen, Anne, additional, Kutila, Anu, additional, Vasala, Kaija, additional, Lehtonen, Päivi, additional, Penttilä, Karri, additional, Kuittinen, Taru, additional, Nousiainen, Tapio, additional, Pelkonen, Jukka, additional, Mäntymaa, Pekka, additional, and Jantunen, Esa, additional

Published
2014
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38. Old enemies in new disguises: emergence of Enterococcus faecium as a significant clinical problem at an adult haematology ward.

Author

Hämäläinen, Sari, Pentikäinen, Jaana, Reijula, Jori, Mauranen, Ella, Koivula, Irma, Lindholm, Laura, Juutilainen, Auni, Nousiainen, Tapio, Pyörälä, Marja, Vuopio, Jaana, and Jantunen, Esa

Subjects
EPIDEMICS, HEMATOLOGY, HOSPITAL wards, ENTEROCOCCUS faecium
Abstract

The article reports that since 1991, Enterococcus faecium have been listed as the second leading nosocomial pathogen and are among the five most common causative agents of bloodstream infections.The issue of the emergence of Enterococcus faecium as a significant clinical problem at an adult haematology ward is discussed.

Published
2017
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45. Ex VivoDrug Sensitivity Testing to Predict Response to Venetoclax + Azacitidine in Acute Myeloid Leukemia: Interim Results of the Prospective Multicenter Phase II Venex Trial

Author

Kuusanmäki, Heikki, Kytölä, Sari, Vänttinen, Ida, Ranta, Amanda, Ruokoranta, Tanja, Holopainen, Annasofia, Koskela, Sirpa, Kuusisto, Milla E.L., Porkka, Kimmo, Räty, Riikka, Västrik, Imre, Wennerberg, Krister, Heckman, Caroline A., Ettala, Pia, Pyörälä, Marja, Rimpiläinen, Johanna, Siitonen, Timo, and Kontro, Mika

Abstract

Background

Published
2021
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46. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia.

Author

Kuusanmäki H, Kytölä S, Vänttinen I, Ruokoranta T, Ranta A, Huuhtanen J, Suvela M, Parsons A, Holopainen A, Partanen A, Kuusisto MEL, Koskela S, Räty R, Itälä-Remes M, Västrik I, Dufva O, Siitonen S, Porkka K, Wennerberg K, Heckman CA, Ettala P, Pyörälä M, Rimpiläinen J, Siitonen T, and Kontro M

Subjects
Humans, Prospective Studies, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute drug therapy, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use
Abstract

The BCL-2 inhibitor venetoclax has revolutionized the treatment of acute myeloid leukemia (AML) in patients not benefiting from intensive chemotherapy. Nevertheless, treatment failure remains a challenge, and predictive markers are needed, particularly for relapsed or refractory AML. Ex vivo drug sensitivity testing may correlate with outcomes, but its prospective predictive value remains unexplored. Here we report the results of the first stage of the prospective phase II VenEx trial evaluating the utility and predictiveness of venetoclax sensitivity testing using different cell culture conditions and cell viability assays in patients receiving venetoclax-azacitidine. Participants with de novo AML ineligible for intensive chemotherapy, relapsed or refractory AML, or secondary AML were included. The primary endpoint was the treatment response in participants showing ex vivo sensitivity and the key secondary endpoints were the correlation of sensitivity with responses and survival. Venetoclax sensitivity testing was successful in 38/39 participants. Experimental conditions significantly influenced the predictive accuracy. Blast-specific venetoclax sensitivity measured in conditioned medium most accurately correlated with treatment outcomes; 88% of sensitive participants achieved a treatment response. The median survival was significantly longer for participants who were ex vivo-sensitive to venetoclax (14.6 months for venetoclax-sensitive patients vs. 3.5 for venetoclax-insensitive patients, P<0.001). This analysis illustrates the feasibility of integrating drug-response profiling into clinical practice and demonstrates excellent predictivity. This trial is registered with ClinicalTrials.gov identifier: NCT04267081.

Published
2023
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47. Impact of the number of cryopreserved CD34 + cells in the infused blood grafts on hematologic recovery and survival in myeloma patients after autologous stem cell transplantation: Experience from the GOA study.

Author

Partanen A, Turunen A, Silvennoinen R, Valtola J, Pyörälä M, Siitonen T, Sikiö A, Putkonen M, Sankelo M, Penttilä K, Kuittinen T, Mäntymaa P, Pelkonen J, Jantunen E, and Varmavuo V

Subjects
Humans, Hematopoietic Stem Cell Mobilization, Transplantation, Autologous, Prospective Studies, Antigens, CD34 metabolism, Cryopreservation, Graft Survival, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy, Heterocyclic Compounds pharmacology
Abstract

Background: Prospective data on the impact of CD34 + cell loss during cryopreservation and the amount of cryopreserved CD34 + cells infused after high-dose therapy on hematologic recovery and post-transplant outcome in multiple myeloma (MM) are scarce., Patients and Methods: This post-hoc study aimed to investigate factors associating with CD34 + cell loss during cryopreservation and the effects of the infusion of a very low number (<1.0 × 10 6 /kg, group A), low number (1-1.9 × 10 6 /kg, group B), and optimal number (≥2 × 10 6 /kg, group C) of thawed viable CD34 + cells on hematologic recovery, progression free survival, and overall survival after autologous stem cell transplantation among 127 patients with MM., Results: In group C, pegfilgrastim use (P = 0.001), plerixafor use (P = 0.039), and older age ≥ 60 years (P = 0.026) were associated with less loss of CD34 + cells during cryopreservation. Better mobilization efficacy correlated with greater CD34 + cell loss in group B (P = 0.013 and P = 0.001) and in group C (P < 0.001 and P < 0.001). Early platelet engraftment was slowest in group A (20 d vs 12 d in group B vs 11 d in group C, P = 0.003). The infused viable CD34 + cell count <1.0 × 10 6 /kg seemed not to have influence on PFS (P = 0.322) or OS (P = 0.378) in MM patients., Conclusions: Cryopreservation impacts significantly on the CD34 + cell loss. A very low number of graft viable CD34 + cells did not affect PFS or OS., (© 2022 Wiley Periodicals LLC.)

Published
2023
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48. Autologous stem cell transplantation in peripheral T-cell lymphoma: better mobilization of blood CD34 + cells is associated with improved survival.

Author

Partanen A, Turunen A, Valtola J, Pyörälä M, Vasala K, Kuittinen O, Kuitunen H, Penttilä K, Kuittinen T, Mäntymaa P, Pelkonen J, Varmavuo V, and Jantunen E

Subjects
Antigens, CD34, Granulocyte Colony-Stimulating Factor, Hematopoietic Stem Cell Mobilization, Humans, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Lymphoma, T-Cell, Peripheral therapy, Peripheral Blood Stem Cell Transplantation
Published
2020
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