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Article ; Online: Splenic rupture in a plasma cell leukemia, mobilized with G-CSF for autologous stem cell transplant.

Funes, Consuelo / Garcia-Candel, Faustino / Majado, Maria Juliana / González-García, Consuelo / Bas, Agueda / Salido, Eduardo / Moraleda, Jose M / Morales, Alfonso

Journal of clinical apheresis

2010 Volume 25, Issue 4, Page(s) 223–225

Abstract: Splenic rupture (SR) is a rare adverse event observed in patients treated with G-CSF as a peripheral hematopoietic stem cell (PHSC) mobilizing agent, mostly in myeloma multiple and amiloidosis; to date, to our knowledge, it has not been previously ... ...

Abstract	Splenic rupture (SR) is a rare adverse event observed in patients treated with G-CSF as a peripheral hematopoietic stem cell (PHSC) mobilizing agent, mostly in myeloma multiple and amiloidosis; to date, to our knowledge, it has not been previously described in plasma-cell leukemia (PCL). We report a case of a woman with PCL, who presented a SR after PHSC mobilization with Cyclophosphamide+G-CSF. The spleen removed showed hematopoietic foci and amiloid material. In the course of a second mobilization, 2 months after, the patient died from sepsis. We considered it important to report this case, in order to keep in mind the possibility of SR in patients with malignant gammopathy.
MeSH term(s)	Fatal Outcome ; Female ; Granulocyte Colony-Stimulating Factor/adverse effects ; Hematopoietic Stem Cell Mobilization/methods ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Leukemia, Plasma Cell/complications ; Middle Aged ; Splenic Rupture/etiology ; Splenomegaly/chemically induced ; Transplantation, Autologous
Chemical Substances	Granulocyte Colony-Stimulating Factor (143011-72-7)
Language	English
Publishing date	2010
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	604912-6
ISSN	1098-1101 ; 0733-2459
ISSN (online)	1098-1101
ISSN	0733-2459
DOI	10.1002/jca.20233
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Article: Dock10, a novel CZH protein selectively induced by interleukin-4 in human B lymphocytes.

Yelo, Estefanía / Bernardo, María Victoria / Gimeno, Lourdes / Alcaraz-García, María José / Majado, María Juliana / Parrado, Antonio

Molecular immunology

2008 Volume 45, Issue 12, Page(s) 3411–3418

Abstract: The Dock or CZH proteins are a family of activators for Rho GTPase proteins. The Zizimin subfamily is composed of three members: Dock9, Dock10, and Dock11. We have identified DOCK10 as an interleukin-4 (IL4)-inducible gene in chronic lymphocytic ... ...

Abstract	The Dock or CZH proteins are a family of activators for Rho GTPase proteins. The Zizimin subfamily is composed of three members: Dock9, Dock10, and Dock11. We have identified DOCK10 as an interleukin-4 (IL4)-inducible gene in chronic lymphocytic leukemias (CLLs). Subsequently, we have obtained the full-length cDNA sequence, which encodes a 2180 amino acid protein. Dock9 (2069 amino acids) and Dock11 (2073 amino acids) share more identity between them (58%) than with Dock10 (52% and 50%, respectively). Among normal human tissues, DOCK10 and DOCK11 mRNAs were mainly expressed in peripheral blood (PB) leukocytes. Dock10 protein was expressed at similar levels in normal PB-B and PB-T cells. Dock10 protein levels were heterogeneous in CLLs. IL4 consistently increased Dock10 mRNA and protein levels in CLL and normal PB-B cells. In contrast, IL4 did not affect the levels of Dock10 expression in normal PB-T cells. IL4 neither increased DOCK9 or DOCK11 mRNA levels in CLL cells. Dock10 protein distributed in the cytoplasm and nucleus of CLL cells, and IL4 increased its expression in both cellular compartments. The rapid and distinctive induction of Dock10 expression by IL4 in CLL and normal PB-B cells suggests a role for Dock10 in IL4-induced B-cell activation. Dock10 could represent a point of convergence for IL4 signalling and small Rho GTPase function in B cells.
MeSH term(s)	Amino Acid Sequence ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; Cloning, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Guanine Nucleotide Exchange Factors/chemistry ; Guanine Nucleotide Exchange Factors/genetics ; Guanine Nucleotide Exchange Factors/metabolism ; Humans ; Interleukin-4/pharmacology ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Lymphocyte Subsets/drug effects ; Molecular Sequence Data ; Protein Transport/drug effects ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid
Chemical Substances	Dock10 protein, human ; Guanine Nucleotide Exchange Factors ; RNA, Messenger ; Interleukin-4 (207137-56-2)
Language	English
Publishing date	2008-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2008.04.003
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Article ; Online: An automatic wash method for dimethyl sulfoxide removal in autologous hematopoietic stem cell transplantation decreases the adverse effects related to infusion.

Sánchez-Salinas, Andrés / Cabañas-Perianes, Valentín / Blanquer, Miguel / Majado, María Juliana / Insausti, Carmen Luisa / Monserrat, Jorge / Sánchez-Ibáñez, Maria Victoria / Menchón, Pilar / García-Hernández, Ana / Gómez-Espuch, Joaquín / Morales, Alfonso / Moraleda, José M

Transfusion

2012 Volume 52, Issue 11, Page(s) 2382–2386

Abstract: Background: Products cryopreserved with dimethyl sulfoxide (DMSO) in stem cell transplant (SCT) often cause many adverse effects during their infusion (major cardiovascular events, dyspnea … even death). These are especially frequent in pediatric ... ...

Abstract	Background: Products cryopreserved with dimethyl sulfoxide (DMSO) in stem cell transplant (SCT) often cause many adverse effects during their infusion (major cardiovascular events, dyspnea … even death). These are especially frequent in pediatric patients. We tested if a fully automated and closed wash procedure (Sepax S-100, Biosafe) allowed us to maintain the absolute CD34+ cell number, cell viability, and engraftment potential, decreasing the untoward reactions. Study design and methods: Forty-six washes of DMSO cryopreserved peripheral blood hematopoietic progenitor (HP) apheresis were studied. Blood aliquots were taken both after thawing and after washing to assess the total nucleated and CD34+ cell counts, as well as cell viability. The washed products were infused in 26 autologous SCTs (ASCTs). Results were compared with the 53 previous SCTs performed without DMSO removal. Results: After washing there were no significant differences between the pre- and postwashing CD34+ cell counts (p=0.08) or viability (p=0.68). No significant differences were observed between washed and nonwashed infusions in relation to the day of the neutrophil (p=0.46) and platelet (p=0.26) engraftment. One adverse event, abdominal pain, occurred during the washed cells infusions. When compared with the 14 untoward reactions that took place during the nonwashed HP infusions, significance was reached (p=0.00043). Conclusions: The automatic method described is effective in terms of CD34+ cell recovery and viability in ASCT. Moreover, Sepax decreased significantly the untoward reactions during the infusion.
MeSH term(s)	Adult ; Aged ; Blood Component Removal ; Blood Preservation/adverse effects ; Blood Preservation/methods ; Blood Transfusion, Autologous ; Cell Survival/drug effects ; Child ; Child, Preschool ; Cryoprotective Agents/adverse effects ; Cryoprotective Agents/isolation & purification ; Dimethyl Sulfoxide/adverse effects ; Dimethyl Sulfoxide/isolation & purification ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cell Transplantation/standards ; Hodgkin Disease/therapy ; Humans ; Lymphoma, Non-Hodgkin/therapy ; Male ; Middle Aged ; Multiple Myeloma/therapy
Chemical Substances	Cryoprotective Agents ; Dimethyl Sulfoxide (YOW8V9698H)
Language	English
Publishing date	2012-11
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/j.1537-2995.2012.03585.x
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Article ; Online: Human and mouse DOCK10 splicing isoforms with alternative first coding exon usage are differentially expressed in T and B lymphocytes.

Alcaraz-García, María José / Ruiz-Lafuente, Natalia / Sebastián-Ruiz, Silvia / Majado, María Juliana / González-García, Consuelo / Bernardo, María Victoria / Alvarez-López, María Rocío / Parrado, Antonio

Human immunology

2011 Volume 72, Issue 7, Page(s) 531–537

Abstract: DOCK10 is a member of the dedicator of cytokinesis (DOCK) family of Rho GTPase activators preferentially expressed in lymphocytes. In this paper, we analyzed DOCK10 mRNA diversity produced because of alternative splicing. Alternative first coding exon ... ...

Abstract	DOCK10 is a member of the dedicator of cytokinesis (DOCK) family of Rho GTPase activators preferentially expressed in lymphocytes. In this paper, we analyzed DOCK10 mRNA diversity produced because of alternative splicing. Alternative first coding exon usage led to 2 main protein-coding transcripts, DOCK10.1 and DOCK10.2. Full-length cDNA clones of both isoforms were obtained from both normal human peripheral blood mononuclear cells and mouse spleen for the first time for human DOCK10.1, mouse DOCK10.1, and mouse DOCK10.2. Human and mouse DOCK10.1 clones corresponded to the protein coding assemblies provided by the National Center for Biotechnology Information as Reference Sequences for DOCK10. Our analysis especially focused on human cDNA clones, of which 63% were alternatively spliced forms involving diverse exons and introns. DOCK10.1 expression was enriched in normal T cells, and DOCK10.2 expression was enriched in normal B cells and chronic lymphocytic leukemia (CLL) B cells. Both isoforms were upregulated in response to interleukin-4 in B cells, both normal and CLL, but not in T cells. Our data suggest that cell-specific mechanisms regulate expression of the alternative first exon variants of DOCK10 in vertebrates.
MeSH term(s)	Alternative Splicing/genetics ; Amino Acid Sequence ; Animals ; B-Lymphocytes/metabolism ; Cell Line, Tumor ; Exons/genetics ; Gene Expression Regulation/drug effects ; Guanine Nucleotide Exchange Factors/genetics ; Guanine Nucleotide Exchange Factors/metabolism ; HL-60 Cells ; HeLa Cells ; Hep G2 Cells ; Humans ; Immunologic Factors/pharmacology ; Interleukin-4/pharmacology ; Jurkat Cells ; K562 Cells ; Mice ; Molecular Sequence Data ; Polymorphism, Single Nucleotide/genetics ; Protein Isoforms/genetics ; T-Lymphocytes/metabolism ; Transcription, Genetic
Chemical Substances	DOCK10 protein, mouse ; Dock10 protein, human ; Guanine Nucleotide Exchange Factors ; Immunologic Factors ; Protein Isoforms ; Interleukin-4 (207137-56-2)
Language	English
Publishing date	2011-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2011.03.024
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Article ; Online: Large-volume-apheresis facilitates autologous transplantation of hematopoietic progenitors in poor mobilizer patients.

Majado, Maria Juliana / Minguela, Alfredo / González-García, Consuelo / Salido, Eduardo / Blanquer, Miguel / Funes, Consuelo / Insausti, Carmen Luisa / García-Hernández, Ana María / Moraleda, José María / Morales, Alfonso

Journal of clinical apheresis

2009 Volume 24, Issue 1, Page(s) 12–17

Abstract: Given that pre-apheresis CD34(+) cell count (PA-CD34) predicts the apheresis' yield, a minimum of 5 to 20 PA-CD34/microl is required in many institutions to initiate cell collection. The aim of this study was to clarify whether large-volume-apheresis ( ... ...

Abstract	Given that pre-apheresis CD34(+) cell count (PA-CD34) predicts the apheresis' yield, a minimum of 5 to 20 PA-CD34/microl is required in many institutions to initiate cell collection. The aim of this study was to clarify whether large-volume-apheresis (LVA) could facilitate progenitor cell transplantation in patients with low PA-CD34. Apheresis was initiated in 226 patients, disregarding PA-CD34, at days: +5 in G-CSF, +10 in cyclophosphamide+G-CSF, and +15 to +20 in other chemotherapy+G-CSF mobilization, when leucocytes >2.5 x 10(9)/L. Four times the blood volume was processed. Patients were grouped according to their PA-CD34: >or=10/microl (group-A, n = 143); <10/microl but >or=5/microl (group-B, n = 40) and <5/microl (group-C, n = 43). No differences were found in diagnoses, gender, age, previous treatments or mobilization regimen between groups. Enough CD34(+) cells (>1.9 x 10(6)/kg) were obtained in 31 patients (72%) from group-C, although in this group two mobilizations were needed in 20 patients (46.5%), compared to 5 (3.5%) and 1 (2.5%) in groups A and B, respectively (P < 0.01). Evenly three apheresis or more were required in 28 patients (65.1%) from group-C, compared to 8 (5.6%) and 6 (15.0%) in groups A and B, respectively (P < 0.01). In conclusion LVA can facilitate autologous transplantation in poor-mobilizer-patients, low PA-CD34 should not be an inflexible exclusion factor.
MeSH term(s)	Adolescent ; Adult ; Aged ; Antigens, CD34/analysis ; Blood Component Removal/methods ; Child ; Child, Preschool ; Cyclophosphamide/administration & dosage ; Female ; Granulocyte Colony-Stimulating Factor/administration & dosage ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Mobilization/methods ; Hematopoietic Stem Cell Mobilization/standards ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Treatment Outcome ; Young Adult
Chemical Substances	Antigens, CD34 ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2009
Publishing country	United States
Document type	Controlled Clinical Trial ; Journal Article
ZDB-ID	604912-6
ISSN	1098-1101 ; 0733-2459
ISSN (online)	1098-1101
ISSN	0733-2459
DOI	10.1002/jca.20191
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Article ; Online: Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: a pilot safety study.

Blanquer, Miguel / Moraleda, Jose M / Iniesta, Francisca / Gómez-Espuch, Joaquín / Meca-Lallana, José / Villaverde, Ramón / Pérez-Espejo, Miguel Ángel / Ruíz-López, Francisco José / García Santos, José María / Bleda, Patricia / Izura, Virginia / Sáez, María / De Mingo, Pedro / Vivancos, Laura / Carles, Rafael / Jiménez, Judith / Hernández, Joaquín / Guardiola, Julia / Del Rio, Silvia Torres /

Antúnez, Carmen / De la Rosa, Pedro / Majado, Maria Juliana / Sánchez-Salinas, Andrés / López, Javier / Martínez-Lage, Juan Francisco / Martínez, Salvador

Stem cells (Dayton, Ohio)

2012 Volume 30, Issue 6, Page(s) 1277–1285

Abstract: The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) ... ...

Abstract	The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity.
MeSH term(s)	Adult ; Amyotrophic Lateral Sclerosis/pathology ; Amyotrophic Lateral Sclerosis/surgery ; Bone Marrow Cells/pathology ; Bone Marrow Transplantation/methods ; Female ; Humans ; Male ; Middle Aged ; Motor Neurons/pathology ; Nerve Degeneration/pathology ; Pilot Projects ; Spinal Cord/pathology ; Spinal Cord/surgery
Language	English
Publishing date	2012-06
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1002/stem.1080
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Article ; Online: Splenic rupture in a plasma cell leukemia, mobilized with G-CSF for autologous stem cell transplant.

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Article: Dock10, a novel CZH protein selectively induced by interleukin-4 in human B lymphocytes.

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Article ; Online: An automatic wash method for dimethyl sulfoxide removal in autologous hematopoietic stem cell transplantation decreases the adverse effects related to infusion.

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Article ; Online: Human and mouse DOCK10 splicing isoforms with alternative first coding exon usage are differentially expressed in T and B lymphocytes.

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Article ; Online: Large-volume-apheresis facilitates autologous transplantation of hematopoietic progenitors in poor mobilizer patients.

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Article ; Online: Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: a pilot safety study.

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