WO1998020932A2 - Conditioning for allogeneic stem cell transplantation - Google Patents

Conditioning for allogeneic stem cell transplantation Download PDF

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Publication number
WO1998020932A2
WO1998020932A2 PCT/US1997/020946 US9720946W WO9820932A2 WO 1998020932 A2 WO1998020932 A2 WO 1998020932A2 US 9720946 W US9720946 W US 9720946W WO 9820932 A2 WO9820932 A2 WO 9820932A2
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WIPO (PCT)
Prior art keywords
patient
donor
host
regimen
allogeneic
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Ceased
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PCT/US1997/020946
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English (en)
French (fr)
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WO1998020932A3 (en
Inventor
Shimon Slavin
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Hadasit Medical Research Services and Development Co
Baxter International Inc
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Hadasit Medical Research Services and Development Co
Baxter International Inc
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Application filed by Hadasit Medical Research Services and Development Co, Baxter International Inc filed Critical Hadasit Medical Research Services and Development Co
Priority to EP97949457A priority Critical patent/EP1011694A4/en
Priority to AU71785/98A priority patent/AU7178598A/en
Priority to IL12957397A priority patent/IL129573A0/xx
Priority to JP52288698A priority patent/JP2002514193A/ja
Priority to CA002271464A priority patent/CA2271464A1/en
Publication of WO1998020932A2 publication Critical patent/WO1998020932A2/en
Anticipated expiration legal-status Critical
Publication of WO1998020932A3 publication Critical patent/WO1998020932A3/en
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
    • A61K40/22—Immunosuppressive or immunotolerising
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/418—Antigens related to induction of tolerance to non-self
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0647—Haematopoietic stem cells; Uncommitted or multipotent progenitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/48—Blood cells, e.g. leukemia or lymphoma
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/49—Breast
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/51—Stomach
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the invention features a method of treating a human patient having a pathogenic cell disease.
  • the method includes treating the patient with a conditioning regimen that retains a functional population of the patient's hematopoietic stem cells.
  • the method also involves administering a preparation that includes allogeneic stem cells from a donor to the patient under conditions effective for inducing host anti -donor unresponsiveness .
  • the regimen can be a m/L conditioning regimen or a -/L conditioning regimen.
  • the allogeneic stem cells are peripheral blood stem cells, cord blood stem cells or bone marrow stem cells.
  • the invention features treating a patient having a pathogenic cell disease with a conditioning regimen that retains a functional population of the patient's T lymphocytes.
  • This second method also includes administering a preparation that includes allogeneic stem cells from a donor to the patient under conditions effective for inducing host anti-donor unresponsiveness.
  • the regimen can be a M/- or a M/l conditioning regimen.
  • myeloablative as used herein includes any therapy that eliminates, through cell killing or cell inactivation, substantially all the hematopoietic stem cells of host origin. "Myeloablative” is herein referred to as "M” .
  • the elimination may be short-term or long-term.
  • M/- refers to a conditioning regimen that is myeloablative but that does not reduce the patient's T lymphocytes.
  • a human patient with a pathogenic cell disease is treated with a conditioning regimen that retains a functional population of the patient's hematopoietic stem cells.
  • Retention of a functional stem cell population allows the patient to avoid commonly encountered clinical effects of cytopenia, for example sepsis and fungal infections due to neutropenia, susceptibility to life- threatening parasites such as Pneumocystis carinii and bleeding due to thrombocytopenia.
  • the patient retains at least about 20% of the functional hematopoietic stem cell population, more preferably at least about 50%, and most preferably at least about 90%, of the functional stem cell population.
  • the conditioning regimens applicable to Method 1 can be classified as m/L or -/L conditioning regimens .
  • Busulfan 4mg/kg/day for two consecutive days (days -6 and -5)
  • an anti-GVHD agent may not be necessary if the veto capacity of the donor-derived preparation is adequately balanced by the veto capacity of the host patient.
  • the veto capacities can be balanced by adjusting the veto capacity of the donor-derived preparation to correspond to the conditioning regimen of the patient, or vice versa. In situations of mixed chimeras, where donor- and host-derived hematopoietic cells coexist, the veto capacities may be inherently balanced.
  • Engraftment of donor stem cells in the host can be detected by any number of standard methods.
  • the presence of donor markers, such as sex chromosome-specific markers, in the host can be determined, for example, using standard cytogenetic analysis, polymerase chain reaction (PCR) with appropriate primers, variable number of tandem repeats-PCR (VNTR-PCR) , microsatelite markers or other finger-printing techniques, or fluorescence in situ hybridization (FISH) .
  • Host-donor chimerism can also be determined by determining the percentage of donor-type cells in host blood using, for example, standard complement-dependent microcytotoxicity tests.
  • allo-CT is performed after a desired level of anti-donor unresponsiveness has been induced in the host, with the allo-CT functioning to generate or amplify the graft versus pathogenic cell effect. Additionally, allo-CT can increase the proportion of donor cells in the host by causing further displacement of host hematopoietic stem cells.
  • a myeloablative (M/-) or (M/l) conditioning regimen may be used. These regimens substantially reduce the patient's functional hematopoietic stem cell population while retaining substantially all (M/-) or a substantial fraction (M/l) of the functional T lymphocyte population. As a consequence, a patient treated with an M/- or M/l conditioning regimen has a particularly high veto capacity mediated by residual T lymphocytes.
  • Suitable myeloablative conditioning regimens can include administration of myeloablative doses of one or more of the myeloablative agents described above.
  • a typical conditioning regimen under Method 2 can be summarized as follows :
  • Busulfan 4mg/kg/day for four consecutive days (days -4 to -1) It is to be understood that the use of busulfan at this dosing schedule is illustrative only, and that other agents and dosing schedules having similar effects on the patient can be employed.
  • Other conditioning regimens may involve melphalan (120-240 mg/m 2 in 1 or 2 divided doses) , thiotepa (10 mg/kg in 1 or 2 divided doses) , high dose hydroxyurea (3-6g/day until myeloablation is accomplished) or other variations of myleran such as dimethyl -myleran .
  • Dibromomanitol (DBM) may also be substituted for busulfan.
  • allo-CT may also be administered to the patient following induction of host anti-donor unresponsiveness and in the absence of significant GVHD.
  • a donor hematopoietic stem cell preparation for a particular patient .
  • such preparations can be considered to possess a "veto" capacity defined by the ability of cells in the preparation to veto the anti -donor activity of T lymphocytes in the host patient.
  • T lymphocytes in the stem cell preparation possess a significantly higher veto activity compared to the stem cells. Nevertheless, it appears that stem cells do have a relatively weak, but not insignificant, veto activity.
  • Host and donor immunocompetent T cells that possess the most effective veto capacity can also cause untowards rejection and GVHD; thus, their numbers must be carefully balanced.
  • donor stem cell preparations also can be tailored to the conditioning regimens of Method 2, where the patient retains a functional population of T lymphocytes.
  • the donor-derived stem cell preparation typically is adjusted to have a relatively high veto capacity, balancing with the high veto capacity of the host patient. This can be accomplished by including high numbers of purified stem cells, or stem cells enriched for T cells.
  • the methods described herein may be safely offered to patients in all age groups with low anticipated incidence of immediate and long-term complications that result commonly from conventional transplants when myeloablation is combined with lymphoablation (M/L) .
  • M/L lymphoablation
  • Donor Cell Infusion The patient received 7.79 x IO 8 cells/kg G-CSF mobilized allo-PBSCT from her HLA-matched sister.
  • IP Interstitial Pneumonitis
  • Hb hemoglobin
  • Hb remained low (median 6.5 g/dl, range 5.4-7.0 g/dl) , and serum ferritin levels rose from 437 to 700 ⁇ g/1.
  • the patient displayed normal growth and development (percentile 50) , although spleen size increased gradually to 4 cm below the left coastal margin and echo cardiogram showed disturbed left ventricle function.
  • a ⁇ -globin gene mutation assay was performed on cultured erythroid colonies, +/- erythropoietin (Epo) .
  • Epo erythropoietin
  • Patient 6 G.S. is a 50 -year-old woman. She had a skin malignant melanoma over the shoulder that was removed and she received no further therapy. Three years later, a mass in the left axilla was found. She had wide excision of the mass including axillary lymph node and nuchal lymph node. Following surgery, she was treated with local radiation of 8,000 rads .
  • Pre-transplant conditioning consisted of rabbit anti-human thymocyte globulin (ATG- Fresenius S, Bad Homburg, Germany, 10 mg/kg/day) from day -8 to day -5 and cyclophosphamide (50 mg/kg/day) from day -4 to day -1.
  • IV CSA (3 mg/kg/day) was administered from day -1 as the only GVHD prophylactic drug.
  • the patient received allogeneic peripheral blood stem cells (2.4 x 10 s CD34 + cells/kg out of a total number 5.5 x 10 s nucleated cells/kg) mobilized by subcutaneous injections of G-CSF 10 ⁇ g/kg/day x 5 days) . Engraftment was documented on day +12, with a white blood cell count of 1 x 10 9 /L and granulocyte count of >0.5 x 10 9 /L. From day +13 platelet count was above 25 x 10 9 /L.

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PCT/US1997/020946 1996-11-15 1997-11-14 Conditioning for allogeneic stem cell transplantation Ceased WO1998020932A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP97949457A EP1011694A4 (en) 1996-11-15 1997-11-14 TREATMENT FOR ALLOGENIC STEM CELL TRANSPLANTATION
AU71785/98A AU7178598A (en) 1996-11-15 1997-11-14 Conditioning for allogeneic stem cell transplantation
IL12957397A IL129573A0 (en) 1996-11-15 1997-11-14 Conditioning for allogeneic stem cell transplantation
JP52288698A JP2002514193A (ja) 1996-11-15 1997-11-14 同種幹細胞移植のためのコンディショニング
CA002271464A CA2271464A1 (en) 1996-11-15 1997-11-14 Conditioning for allogeneic stem cell transplantation

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US3083396P 1996-11-15 1996-11-15
US60/030,833 1996-11-15
US3702497P 1997-01-31 1997-01-31
US60/037,024 1997-01-31

Publications (2)

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WO1998020932A2 true WO1998020932A2 (en) 1998-05-22
WO1998020932A3 WO1998020932A3 (en) 1999-10-21

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PCT/US1997/020946 Ceased WO1998020932A2 (en) 1996-11-15 1997-11-14 Conditioning for allogeneic stem cell transplantation

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US (1) US6544787B1 (enExample)
EP (1) EP1011694A4 (enExample)
JP (1) JP2002514193A (enExample)
CA (1) CA2271464A1 (enExample)
IL (1) IL129573A0 (enExample)
WO (1) WO1998020932A2 (enExample)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002529426A (ja) * 1998-11-09 2002-09-10 アイデック・ファーマシューティカルズ・コーポレイション キメラ抗ｃｄ２０抗体を用いた、循環腫瘍細胞に関連した血液学的悪性疾患の治療
JP2002534083A (ja) * 1998-12-31 2002-10-15 ハダシット メディカル リサーチ サービス アンド デベロップメント リミテッド 骨髄機能廃絶性ではない寛容原性の処置
US6558662B2 (en) 1997-11-14 2003-05-06 The General Hospital Corporation Treatment of hematologic disorders
US8673321B2 (en) 2006-09-15 2014-03-18 The Johns Hopkins University Cyclophosphamide in combination with anti-idiotypic vaccines
WO2014128611A1 (en) * 2013-02-20 2014-08-28 Novartis Ag Treatment of graft versus host disease in transplant patients
US9026372B2 (en) 2007-11-21 2015-05-05 Accentia Biopharmaceuticals, Inc. Methods for providing a system of care for a high-dose oxazaphosphorine drug regimen
US9279803B2 (en) 2006-09-15 2016-03-08 The Johns Hopkins University Method of identifying patients not suitable for high-dose cyclophosphamide treatment
US9539267B2 (en) 2006-09-15 2017-01-10 The Johns Hopkins University Cyclophosphamide in combination with immune therapeutics
WO2020092694A3 (en) * 2018-10-31 2020-06-11 Magenta Therapeutics Inc. Methods for hematopoietic stem and progenitor cell transplant therapy
RU2816662C1 (ru) * 2023-01-09 2024-04-02 Федеральное государственное бюджетное образовательное учреждение высшего образования "Тихоокеанский государственный медицинский университет" Министерства здравоохранения Российской Федерации Способ консервативной мирингопластики с использованием "КОЛЛОСТ" мембраны

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050042679A1 (en) * 1999-04-15 2005-02-24 Monash University Diagnostic indicator of thymic function
US20040258672A1 (en) * 1999-04-15 2004-12-23 Monash University Graft acceptance through manipulation of thymic regeneration
US20040265285A1 (en) * 1999-04-15 2004-12-30 Monash University Normalization of defective T cell responsiveness through manipulation of thymic regeneration
RU2165765C1 (ru) * 2000-01-28 2001-04-27 Туманов Владимир Павлович Способ устранения травматического дефекта барабанной перепонки
US7541184B2 (en) * 2000-02-24 2009-06-02 Invitrogen Corporation Activation and expansion of cells
US7572631B2 (en) 2000-02-24 2009-08-11 Invitrogen Corporation Activation and expansion of T cells
US20060088512A1 (en) * 2001-10-15 2006-04-27 Monash University Treatment of T cell disorders
US20050112122A1 (en) * 2003-09-02 2005-05-26 Greiner Dale L. Generation of hematopoietic chimerism and induction of central tolerance
EP1663308A1 (en) * 2003-09-22 2006-06-07 Xcyte Therapies, Inc Compositions and methods to accelerate hematologic recovery
US20070269412A1 (en) 2003-12-02 2007-11-22 Celavie Biosciences, Llc Pluripotent cells
US20080279812A1 (en) * 2003-12-05 2008-11-13 Norwood Immunology, Ltd. Disease Prevention and Vaccination Prior to Thymic Reactivation
WO2006004592A2 (en) * 2004-05-28 2006-01-12 Mayo Foundation For Medical Education And Research Methods for autologous stem cell transplantation
US20070202077A1 (en) * 2005-12-02 2007-08-30 Brodsky Robert A Use of High-Dose Oxazaphosphorine Drugs for Treating Immune Disorders
US20100215629A1 (en) * 2007-10-12 2010-08-26 Universite Pierre Et Marie Curie (Paris 6) Treatment of tumors using t lymphocyte preparations
WO2009067690A2 (en) * 2007-11-21 2009-05-28 Accentia Biopharmaceuticals, Inc. Methods for safe and effective treatment using oxazaphosphorine drugs
WO2009094456A2 (en) * 2008-01-22 2009-07-30 Johns Hopkins University Use of high-dose, post-transplantation oxazaphosphorine drugs for reduction of transplant rejection
WO2010077313A1 (en) 2008-12-17 2010-07-08 Sand9, Inc. Mechanical resonating structures including a temperature compensation structure
US20100209399A1 (en) * 2009-02-13 2010-08-19 Celavie Biosciences, Llc Brain-derived stem cells for repair of musculoskeletal system in vertebrate subjects
US8604888B2 (en) * 2009-12-23 2013-12-10 Sand 9, Inc. Oscillators having arbitrary frequencies and related systems and methods
US8736388B2 (en) * 2009-12-23 2014-05-27 Sand 9, Inc. Oscillators having arbitrary frequencies and related systems and methods
ES2686424T5 (es) 2010-05-04 2023-03-27 Yeda Res & Dev Inmunoterapia con células alogénicas redireccionadas
MX2014007648A (es) 2011-12-22 2015-03-19 Yeda Res & Dev Una terapia de combinacion para un injerto estable y a largo plazo usando protocolos especificos para agotamiento de celulas t/b.
WO2015054400A2 (en) * 2013-10-08 2015-04-16 Immunogen, Inc. Anti-folr1 immunoconjugate dosing regimens
US10800649B2 (en) 2016-11-28 2020-10-13 Analog Devices International Unlimited Company Planar processing of suspended microelectromechanical systems (MEMS) devices
EP3873502A4 (en) * 2018-11-01 2022-06-29 Children's Hospital Medical Center Reduced intensity conditioning with melphalan
US10843920B2 (en) 2019-03-08 2020-11-24 Analog Devices International Unlimited Company Suspended microelectromechanical system (MEMS) devices
EP3969905A4 (en) * 2019-05-16 2023-06-14 Children's Hospital Medical Center METHODS FOR DETERMINING A CUSTOMIZED FULL DOSE OF MELPHALAN IN A REDUCED-INTENSITY DOSAGE REGIMEN PRIOR TO HEMATOPOIETIC CELL TRANSPLANTATION

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5004681B1 (en) 1987-11-12 2000-04-11 Biocyte Corp Preservation of fetal and neonatal hematopoietic stem and progenitor cells of the blood
US5635156A (en) 1993-09-13 1997-06-03 University Of Pittsburgh Non-lethal methods for conditioning a recipient for bone marrow transplantation
US5514364A (en) 1993-09-13 1996-05-07 University Of Pittsburgh Non-lethal methods for conditioning a recipient for bone marrow transplantation
IL112969A (en) 1994-03-17 2001-05-20 Baxter Int Pharmaceutical compositions for the treatment of cancer comprising allogenic lymphocytes or their combination with a t-cell activator

Cited By (17)

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Publication number Priority date Publication date Assignee Title
US6558662B2 (en) 1997-11-14 2003-05-06 The General Hospital Corporation Treatment of hematologic disorders
US7408039B2 (en) 1997-11-14 2008-08-05 The General Hospital Corporation Kits for treatment of hematologic disorders
US7892578B2 (en) 1997-11-14 2011-02-22 The General Hospital Corporation Treatment of hematologic disorders
JP2010285439A (ja) * 1998-11-09 2010-12-24 Biogen Idec Inc キメラ抗ｃｄ２０抗体を用いた、循環腫瘍細胞に関連した血液学的悪性疾患の治療
JP4842435B2 (ja) * 1998-11-09 2011-12-21 バイオジェン・アイデック・インコーポレイテッド キメラ抗ｃｄ２０抗体を用いた、循環腫瘍細胞に関連した血液学的悪性疾患の治療
JP2002529426A (ja) * 1998-11-09 2002-09-10 アイデック・ファーマシューティカルズ・コーポレイション キメラ抗ｃｄ２０抗体を用いた、循環腫瘍細胞に関連した血液学的悪性疾患の治療
JP2002534083A (ja) * 1998-12-31 2002-10-15 ハダシット メディカル リサーチ サービス アンド デベロップメント リミテッド 骨髄機能廃絶性ではない寛容原性の処置
US9539267B2 (en) 2006-09-15 2017-01-10 The Johns Hopkins University Cyclophosphamide in combination with immune therapeutics
US8673321B2 (en) 2006-09-15 2014-03-18 The Johns Hopkins University Cyclophosphamide in combination with anti-idiotypic vaccines
US9279803B2 (en) 2006-09-15 2016-03-08 The Johns Hopkins University Method of identifying patients not suitable for high-dose cyclophosphamide treatment
US9026372B2 (en) 2007-11-21 2015-05-05 Accentia Biopharmaceuticals, Inc. Methods for providing a system of care for a high-dose oxazaphosphorine drug regimen
WO2014128611A1 (en) * 2013-02-20 2014-08-28 Novartis Ag Treatment of graft versus host disease in transplant patients
AU2014220377B2 (en) * 2013-02-20 2017-05-04 Priothera Limited Treatment of graft versus host disease in transplant patients
EA030783B1 (ru) * 2013-02-20 2018-09-28 Керин Фармасьютикал Ко., Лтд. Способ лечения и/или предупреждения реакции "трансплантат против хозяина" у пациента, подвергаемого трансплантации гемопоэтических стволовых клеток
US11224604B2 (en) 2013-02-20 2022-01-18 Priothera Limited Treatment of graft versus host disease in transplant patients
WO2020092694A3 (en) * 2018-10-31 2020-06-11 Magenta Therapeutics Inc. Methods for hematopoietic stem and progenitor cell transplant therapy
RU2816662C1 (ru) * 2023-01-09 2024-04-02 Федеральное государственное бюджетное образовательное учреждение высшего образования "Тихоокеанский государственный медицинский университет" Министерства здравоохранения Российской Федерации Способ консервативной мирингопластики с использованием "КОЛЛОСТ" мембраны

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US6544787B1 (en) 2003-04-08
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