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T Büchner

Publications and source records attributed to T Büchner.

At least 19 recordsLinked to original sources
PubMed2003

Treatment of relapsed acute promyelocytic leukemia.

By all-trans retinoic acid (ATRA) and chemotherapy over 70% of patients with newly diagnosed acute promyelocytic leukemia (APL) may be cured; 20-30% of patients still relapse and require salvage therapy. For relapsed or refractory APL, a standard treatment has not yet been defined. However, several effective drugs and approaches have been described. Treatment options for relapsed APL include chemotherapy regimens used in the treatment of relapsed acute myeloid leukemia usually combined with ATRA or of other differentiating agents such as liposomal ATRA or synthetic retinoids. Presently, allogeneic peripheral stem cell or bone marrow transplantation is the treatment of choice for younger patients who have a histocompatible donor, as it gives the chance of cure in second or further relapse. For patients without a donor or for those who are not suitable for allogeneic transplantation, autologous stem cell or bone marrow transplantation may offer at least the possibility of a prolongation of remission, if the harvested cells are negative in the RT-PCR of PML/RAR alpha. Arsenic compounds have a high antileukemic effectiveness on APL cells. Arsenic trioxide has recently been approved for relapsed or refractory APL. With this drug, complete hematologic remission rates of 80-92% and long-lasting molecular remissions were achieved in relapsed patients. For patients who do not qualify for these treatment options, monoclonal anti-CD33 antibodies may represent further treatment options.

Antineoplastic Agents↗
PubMed2002

Treatment of severe Candida infections in high-risk patients in Germany: consensus formed by a panel of interdisciplinary investigators.

Now that modern medicine can provide increasing chances of cure to patients with formerly incurable disorders, therapy-related complications play the key role in outcome. Thus, among opportunistic infections, severe candidiasis remains a challenge. A multidisciplinary panel of 20 investigators was formed to find a consensus on antifungal strategies for various underlying conditions in neutropenic and non-neutropenic patients. To record their preferences, the investigators used an anonymous voting system. Among antifungal agents, fluconazole emerged as the major alternative to the classic amphotericin B, being therapeutically at least equivalent but clearly less toxic. Factors that restrict the use of fluconazole include pretreatment with azoles, involvement of resistant species like Candida krusei, and an inability to exclude aspergillosis. Flucytosine can be reasonably combined with both amphotericin B and fluconazole. Within the limited antifungal armamentarium, amphotericin B lipid formulations and itraconazole also appear useful and require further investigation. The general consensus of the group is that antifungal agents should be administered at sufficient dosages, rather early, and often empirically.

Antifungal Agents↗
PubMed2002

Overexpression of vascular endothelial growth factor (VEGF) and its cellular receptor KDR (VEGFR-2) in the bone marrow of patients with acute myeloid leukemia.

Vascular endothelial growth factor (VEGF) and its cellular receptor VEGFR-2 have been implicated as the main endothelial pathway required for tumor neovascularization. However, the importance of the VEGF/VEGFR-2 system for angiogenesis in hematologic malignancies such as AML remains to be elucidated. In 32 patients with newly diagnosed untreated AML, we observed by immunohistochemical analysis of bone marrow biopsies significantly higher levels of VEGF and VEGFR-2 expression than in 10 control patients (P <0.001). In contrast, VEGFR-1 staining levels in AML patients were in the same range as in the controls. Expression of VEGF and VEGFR-2 was significantly higher in patients with a high degree of microvessel density compared to those with a low degree (VEGF: P =0.024; VEGFR-2: P =0.040) and correlated well with bone marrow microvessel density (r(s)=0.566 and 0.609, respectively; P <0.001). Furthermore, in patients who achieved a complete remission following induction chemotherapy VEGFR-2 staining levels decreased into the normal range. In conclusion, our results provide evidence for increased expression of VEGF/VEGFR-2 of leukemic blasts and correlation with angiogenesis in the bone marrow of AML patients. Thus, VEGF/VEGFR-2 might constitute promising targets for antiangiogenic and antileukemic treatment strategies in AML.

Acute Disease↗
PubMed2001

Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia.

The small molecule receptor tyrosine kinase (RTK) inhibitor SU5416 targets the vascular endothelial growth factor receptor 2 and the stem cell factor receptor c-kit. Herein is described the successful treatment of a 65-year-old woman with SU5416, in second relapse of acute myeloid leukemia (AML) and refractory toward standard chemotherapy regimens. After 12 weeks of treatment with SU5416, the blast cell counts (blood and bone marrow) decreased to undetectable levels and the peripheral blood cell counts normalized with the exception of the platelet count (50-80 x 10(9)/L [50-80 x 10(3)/microL]). The duration of the remission is longer than 4 months during maintenance therapy with SU5416. Microvessel density in the patient's bone marrow dropped from 33.4 to 12.3 microvessels/x500-field 8 weeks after SU5416 administration and remains in the normal range. This is the first report of a stable remission achieved after administration of the RTK inhibitor SU5416 in a patient with AML relapse.

Acute Disease↗
PubMed2001

Amplification of ribosomal RNA genes in acute myeloid leukemia.

Gene amplification is a relatively rare event in acute myeloid leukemia (AML). Double minutes (dmin) and homogeneously staining regions are well established phenomena as cytogenetic correlates of gene amplification. Recently, however, two additional mechanisms leading to gene amplification, i.e., segmental jumping translocations and formation of ring chromosomes, have been described. We report four patients with AML, in whom bone marrow cells exhibited amplifications of ribosomal RNA (rRNA) genes in the form of ring chromosomes or a hsr. In two patients, the MLL gene, and in one patient the CBFA2 gene were shown to be co-amplified with rRNA genes. In two of the four patients, multiple copies of alpha-satellite sequences of the centromeres 13 and 21, respectively, were also demonstrated. In three of the four patients, the clinical course was very aggressive, leading to death within 2-8 months. In these three patients, complex karyotype abnormalities were found, whereas the karyotype of Patient 4 was characterized only by supernumerary ring 21 chromosomes of different sizes and a trisomy 8 in half of the metaphases. Modes of origin and clinical significance of the amplification of rRNA genes are discussed.

Acute Disease↗
PubMed2001

Efficacy of fludarabine, intermittent sequential high-dose cytosine arabinoside, and mitoxantrone (FIS-HAM) salvage therapy in highly resistant acute leukemias.

Patients with refractory acute leukemias after intensive induction and salvage attempts have a particularly poor prognosis and therapeutic options are limited. In the current study, the pharmacologically based FIS-HAM regimen was applied, which included fludarabine 15 mg/m2 q 12 h (days 1, 2, 8, and 9), cytosine arabinoside as a 45-min infusion every 3 h at 750 mg/m2 per single application (days 1, 2, 8, and 9), and mitoxantrone 10 mg/m2 (days 3, 4, 10, 11). Twenty-six intensively pretreated patients [median age: 38 years; range: 22-65; 16 cases of acute myeloid leukemia (AML) and 10 of acute lymphoblastic leukemia (ALL)] were included. Of 16 patients with AML, 5 achieved a complete remission (CR, 31%), 1 a partial remission (PR, 6%), 2 were nonresponders (13%), and 8 succumbed to early death (ED, 50%). Of 10 patients with ALL, 5 achieved a CR, 1 a PR, 1 was a nonresponder, and 3 died early. Overall, the CR rate was 38%. The median disease-free survival time was 50 days and median survival 90 days. Two patients underwent allogeneic bone marrow transplantation and are alive after 27 and 28 months. Neutropenia amounted to a median of 46 days. Toxicity WHO III/IV included infection (61%), diarrhea (48%), nausea/vomiting (43%), impairment of heart function (30%), and mucositis (26%). The current data indicate a significant activity of FIS-HAM chemotherapy in advanced acute leukemias. However, due to its pronounced toxicity, this regimen should be restricted to third-line therapy for patients expecting a suitable donor for allogeneic transplantation, and supportive treatment should be optimized.

Acute Disease↗
PubMed2001

Remission induction therapy: the more intensive the better?

Intensive induction therapy in acute myeloid leukemia (AML) as in some other systemic malignancies is a strategy fundamentally different from post-remission strategies. Approaches such as consolidation treatment, prolonged maintenance, and autologous or allogeneic transplantation in first remission are directed against the minimal residual disease in which a malignant cell population has survived induction treatment and shows resistance due to special genetic or kinetic features. In contrast, induction therapy deals with naive tumor cells possibly different from their counterparts in remission in terms of their kinetic status and sensitivity. Therefore, in AML the introduction of intensification strategies into the induction phase of treatment has been suggested as a new step in addition to intensification in the postremission phase. As expected from the dose effects observed in post-remission treatment with high-dose cytarabine (AraC) or longer treatment, similar dose effects have been found in induction treatment both from the incorporation of high-dose AraC and from the double-induction strategy used in patients up to 60 years of age. As a particular effect, patients with poor-risk AML according to an unfavorable karyotype, high LDH in serum, or a delayed response show longer survival following double induction containing high-dose AraC as compared to standard-dose AraC. A corresponding dose effect in the induction treatment of patients aged 60 years and older has been found with daunorubicin 60 vs 30 mg/m2 as part of the thioguanine/ AraC/daunorubicin (TAD) regimen with the higher dosage significantly increasing the response rate and survival in these older patients who represent a poor-risk group as a whole. Thus we have been able to demonstrate both in younger and older patients that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits cumulative toxicity in that repeated courses containing high-dose AraC in the post-remission period lead to long-lasting aplasias of about 6 weeks. Thus after intensive induction treatment, high-dose chemotherapy in remission may be practicable using stem-cell rescue and may contribute to a further improvement in the outcome in poor-risk as well as average-risk patients with AML. These approaches are currently under investigation by the German AML Cooperative Group (AMLCG). "The more intensive the better" is certainly not the way to go in the management of AML and other systemic malignancies but some increase in intensity may be possible and better.

Acute Disease↗
PubMed2001

Current status and perspectives of therapy for acute myeloid leukemia.

Intensification of induction and postremission chemotherapies has resulted in a steady improvement in outcomes for adults with acute myeloid leukemia (AML) over the past two decades. The global response to initial therapy is now in the range of 60% to 80%, with 20% to 30% of patients experiencing long-term disease-free survival. Modern methodologies have revealed that cytogenetic aberrations are closely related to treatment outcome and have allowed subgroups of patients to be identified who have AML with a good, intermediate, or poor prognosis. The actions and interactions of cytogenetics and therapy in determining treatment outcome have been investigated in a series of clinical trials conducted by the German AML Cooperative Group. Evidence is presented that therapy and cytogenetics can independently influence outcome. It is hoped that our increasing understanding of the biological mechanisms that dictate disease characteristics will lead to improved outcomes for patients with AML.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Rhinocerebral zygomycosis in a patient with acute lymphoblastic leukemia.

We report a case of a 28-year-old man with acute lymphoblastic leukemia who developed rhinocerebral zygomycosis during induction chemotherapy. This life-threatening fungal infection is an infrequent cause of neutropenic fever, and is occasionally found in patients with leukemia and lymphoma, or patients with severely compromised defence mechanisms due to other diseases. It is caused by moulds belonging to the Mucoraceae family, and is characterized by local destruction of the affected organ. In our patient, the infection spread from the paranasal sinuses to the right orbit, destroyed intraorbital structures and resulted in blindness within days. Biopsy from the right maxillary sinus was performed and mucormycosis was suspected through microscopic examination. Culture of the resected specimen identified Rhizopus arrhizus as the causing agent. Treatment of zygomycosis should consist of radical surgical debridement of the infected tissue, together with intensive broad-spectrum antimycotic therapy with amphotericin B. What could be learned from this case is, that aggressive approaches to identify the cause of infection is necessary, and that aggressive treatment strategies are inevitable to overcome the infection. Furthermore, treatment of the underlying disease should be continued as soon as possible.

Adult↗
PubMed2001

Cytogenetic subgroups in acute myeloid leukemia differ in proliferative activity and response to GM-CSF.

The current study was undertaken to search for differences in the biology of cytogenetic subgroups in patients with de novo acute myeloid leukemia (AML). In addition, factors influencing the metabolism of cytosine arabinoside (araC) as the key agent of antileukemic activity were assessed. Bone marrow aspirates from 91 patients with newly diagnosed AML in whom karyotypes were successfully obtained were analyzed: (1) for spontaneous proliferative activity by 3H-thymidine (3H-TdR) incorporation; (2) proliferative response to GM-CSF by in vitro incubation of blasts for 48 h with or without GM-CSF (100 U/ml) followed by an additional 4-h exposure to 3H-TdR (0.5 microCi/ml); and (3) parameters of araC metabolism comprising 3H-araC uptake in vitro and the activities of polymerase alpha (poly alpha), deoxycytidine kinase (DCK) and deoxycytidine deaminase (DCD). According to the results of chromosome analyses four cytogenetic subgroups were discriminated: (I) normal karyotypes (n = 38); (II) favorable karyotypes [t8;21), t(15;17), inv(16)] (n = 16); (III) unfavorable karyotypes [inv (3), -5, 5q-, t(6;9), +8, t (9;11), complex abnormalities] (n = 20); (IV) karyotypes of unknown prognostic significance (n = 17). Proliferative activity of leukemic blasts was significantly higher in favorable karyotypes (group II) as compared to cases with unfavorable cytogenetics (group III) with median values and range for 3H-TdR uptake in group II of 2.48 pmol/10(5) cells (0.28-25.8) and in group III of 0.51 pmol/10(5) cells (0.04-7.6) (P = 0.0096). The respective values in group I and group IV were 0.7pmol/10(5) cells (0.0-6.7) and 0.98 pmol/10(5) cells (0.0-4.0), respectively. Inversely, response to GM-CSF, as defined by an increase in 3H-TdR incorporation >1.5- fold over control values after 48h of GM-CSF exposure, was significantly lower for patients with a favorable karyotype (group II) as compared to group I (P = 0.04) and group III (P = 0.013). No significant differences between karyotype groups I, II, III and IV were found for 3H-araC incorporation, nor for the activities of poly alpha, DCK and DCD. These data demonstrate differences in the biology of cytogenetic subgroups in AML which may partly explain the well established differences in clinical outcome.

Acute Disease↗
PubMed2001

Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients.

The clinical significance of complex chromosome aberrations for adults with acute myeloid leukaemia (AML) was assessed in 920 patients with de novo AML who were karyotyped and treated within the German AML Cooperative Group (AMLCG) trials. Complex chromosome aberrations were defined as three or more numerical and/or structural chromosome aberrations excluding translocations t(8;21)(q22;q22), t(15;17)(q22;q11-q12) and inv(16)(p13q22). Complex chromosome anomalies were detected in 10% of all cases with a significantly higher incidence in patients > or = 60 years of age (17.8% vs. 7.8%, P < 0.0001). Clinical follow-up data were available for 90 patients. Forty-five patients were < 60 years of age and were randomly assigned to double induction therapy with either TAD-TAD [thioguanine, daunorubicin, cytosine arabinoside (AraC)] or TAD-HAM (high-dose AraC, mitoxantrone). Twenty-one patients achieved complete remission (CR) (47%), 20 patients (44%) were non-responders and 9% of patients died during aplasia (early death). The median overall survival (OS) was 7 months and the OS rate at 3 years was 12%. Patients receiving TAD-HAM showed a significantly higher CR rate than patients receiving TAD-TAD (56% vs. 23%, P = 0.04). Median event-free survival was less than 1 month in the TAD-TAD group and 2 months in the TAD-HAM group, respectively (P = 0.04), with a median OS of 4.5 months vs. 7.6 months (P = 0.13) and an OS after 3 years of 7.6% vs. 19.6%. Forty-five patients were > or = 60 years of age: 28 of these patient were treated for induction using one or two TAD courses and 17 cases received TAD-HAM with an age-adjusted reduction of the AraC dose. The CR rate was 44%, 38% were non-responders and 18% experienced early death. The median OS was 8 months and the OS rate at 3 years was 6%. In conclusion, complex chromosome aberrations in de novo AML predicted a dismal outcome, even when patients were treated with intensive chemotherapy. Patients under the age of 60 years with complex aberrant karyotypes may benefit from HAM treatment during induction. However, long-term survival rates are low and alternative treatment strategies for remission induction and consolidation are urgently needed.

Acute Disease↗
PubMed2001

Spectral karyotyping and fluorescence in situ hybridization detect novel chromosomal aberrations, a recurring involvement of chromosome 21 and amplification of the MYC oncogene in acute myeloid leukaemia M2.

Recurring chromosomal aberrations are of aetiological, diagnostic, prognostic and therapeutic importance in acute myeloid leukaemia (AML). However, aberrations are detected in only two thirds of AML cases at diagnosis and recurrent balanced translocations in only 50%. Spectral karyotyping (SKY) enables simultaneous visualization of all human chromosomes in different colours, facilitating the comprehensive evaluation of chromosomal abnormalities. Therefore, SKY was used to characterize 37 cases of newly diagnosed AML-M2, previously analysed using G-banding. In 15/23 patients it was possible to obtain metaphases from viably frozen cells; in 22 additional cases, fixed-cell suspensions were used. Of the 70 chromosomal aberrations identified by SKY, 30 aberrations were detected for the first time, 18 aberrations were redefined and 22 were confirmed. SKY detected two reciprocal translocations, t(X;3) and t(11;19). In five cases, eight structural aberrations resulted in partial gains of chromosome 21, six of which were undetected by G-banding. In 4/5 cases, these resulted in copy number increases for AML1. Amplification of MYC was detected in three cases. Using SKY and FISH, clonal aberrations were identified in 5/18 cases with a presumed normal karyotype; 3/5 aberrations were of known unfavourable prognostic significance. Karyotypes were entered into a custom-designed SKY database, which will be integrated with other cytogenetic and genomic databases.

Chromosome Aberrations↗
PubMed2001

Acute myeloid leukaemia (AML): treatment of the older patient.

Undertreatment of the older patients with acute myeloid leukaemia (AML) can explain, in part, their inferior outcome when compared with that of younger patients. Corresponding to the benefit to patients under the age of 60 from high-dose Ara-C there are also dose effects in those over 60 years old, in particular for daunorubicin in the induction treatment, and for the quantity in terms of duration of postremission treatment. The use of these effects can partly overcome the mostly unfavourable disease biology seen in older age AML patients, which is expressed by the absence of favourable and the over-representation of adverse chromosomal abnormalities as well as by the expression of drug resistance. We recommend an adequate dosage of 60 mg/m(2)daunorubicin for 3 days in combination with standard dose Ara-C and 6-thioguanine given for induction and consolidation, followed by a prolonged monthly maintenance chemotherapy for a duration of at least 1 year. Further improvements in supportive care may help in delivering additional anti-leukaemic cytotoxicity. As a novel approach, non-myeloablative preparative regimens may open up the field of allogeneic transplantation for older patients with AML. Given that the actual median age in this disease is more than 60 years the management of older age AML remains as the major challenge.

Acute Disease↗
PubMed2000

Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways.

Somatic mutations of the receptor tyrosine kinase Flt3 consisting of internal tandem duplications (ITD) occur in 20% of patients with acute myeloid leukemia. They are associated with a poor prognosis of the disease. In this study, we characterized the oncogenic potential and signaling properties of Flt3 mutations. We constructed chimeric molecules that consisted of the murine Flt3 backbone and a 510-base pair human Flt3 fragment, which contained either 4 different ITD mutants or the wild-type coding sequence. Flt3 isoforms containing ITD mutations (Flt3-ITD) induced factor-independent growth and resistance to radiation-induced apoptosis in 32D cells. Cells containing Flt3-ITD, but not those containing wild-type Flt3 (Flt3-WT), formed colonies in methylcellulose. Injection of 32D/Flt3-ITD induced rapid development of a leukemia-type disease in syngeneic mice. Flt3-ITD mutations exhibited constitutive autophosphorylation of the immature form of the Flt3 receptor. Analysis of the involved signal transduction pathways revealed that Flt3-ITD only slightly activated the MAP kinases Erk1 and 2 and the protein kinase B (Akt) in the absence of ligand and retained ligand-induced activation of these enzymes. However, Flt3-ITD led to strong factor-independent activation of STAT5. The relative importance of the STAT5 and Ras pathways for ITD-induced colony formation was assessed by transfection of dominant negative (dn) forms of these proteins: transfection of dnSTAT5 inhibited colony formation by 50%. Despite its weak constitutive activation by Flt3-ITD, dnRas also strongly inhibited Flt3-ITD-mediated colony formation. Taken together, Flt3-ITD mutations induce factor-independent growth and leukemogenesis of 32D cells that are mediated by the Ras and STAT5 pathways. (Blood. 2000;96:3907-3914)

Acute Disease↗
PubMed2000

Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia.

The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. In contrast, only few data are available for hematologic neoplasms. To investigate the role of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies from 62 adults with newly diagnosed, untreated AML (day 0) were evaluated. Further studies were done after the completion of remission induction chemotherapy (day 16 of induction chemotherapy, n = 21; complete remission, n = 20). Microvessels were scored in at least 3 areas (x500 field, 0.126 mm(2)) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for von Willebrand factor and thrombomodulin. Microvessel counts were significantly higher in patients with AML (n = 62) compared with control patients (n = 22): median (interquartile range) 24.0 (21.0-27.8)/x500 field vs 11.2 (10. 0-12.0)/x500 field, respectively (P <.001). On day 16 of induction chemotherapy, microvessel density was reduced by 60% (44-66) (P <. 001) in hypoplastic marrows without residual blasts, in contrast to only 17% (0-37) reduction in hypoplastic marrows with >/= 5% residual blasts (P <.001 for the difference between both groups). Bone marrow biopsies taken at the time of complete remission displayed a microvessel density in the same range as the controls. In conclusion, there is evidence of increased microvessel density in the bone marrow of patients with AML, which supports the hypothesis of an important role of angiogenesis in AML. Furthermore, these findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of AML. (Blood. 2000;95:2637-2644)

Acute Disease↗
PubMed2000

Effective ex vivo generation of megakaryocytic cells from mobilized peripheral blood CD34(+) cells with stem cell factor and promegapoietin.

OBJECTIVE: The additional transplantation of ex vivo-generated megakaryocytic cells might enable the clinician to ameliorate or abrogate high-dose chemotherapy-induced thrombocytopenia. Therefore, the ex vivo expansion of CD34(+) PBPC was systematically studied aiming for an optimum production of megakaryocytic cells. MATERIALS AND METHODS: CD34(+) PBPC were cultured in serum-free medium comparing different (n = 23) combinations of stem cell factor (SCF) (S), IL-1beta (1), IL-3 (3), IL-6 (6), erythropoietin (EPO) (E), thrombopoietin (TPO) (T) and promegapoietin (PMP, a novel chimeric IL-3/TPO receptor agonist). Ex vivo-generated cells were assessed by flow cytometry, morphology, and progenitor cell assays. RESULTS: Addition of TPO to cultures stimulated with S163E, a potent progenitor cell expansion cocktail previously described by our group, effectively induced the generation of CD61(+) cells (day 12: 31.4 +/- 7.9%). The addition of PMP tended to be more effective than TPO +/- IL-3. Whereas EPO was not required to maximize TPO- or PMP-induced megakaryocytic cell production, the use of IL-6 and IL-1beta augmented cellular expansion as well as CD61(+) cell production rates in the majority of cytokine combinations studied. Thus, the most effective CD61(+) cell expansion cocktail consisted of S163 + PMP which resulted in 65.9 +/- 3.0% CD61(+) at day 12 and an overall production of 40.7 +/- 4.5 CD61(+) cells per seeded CD34(+) PBPC. However, the basic 2-factor combination S + PMP also allowed for an effective CD61(+) cell production (day 12 CD61(+) cell production: 15.1 +/- 1.6). Moreover, maximum amplification of CFU-Meg was observed after 7 days using this two-factor cocktail (12.9 +/- 2.6-fold). The majority of CD61(+) cells generated in TPO- or PMP-based medium were low-ploidy 4N and 8N cells, and ex vivo-generated CD61(+), CD41(+), and CD42b(+) cells were mainly double positive for FACS-measured intracellular von Willebrand Factor (vWF) (76.7 +/- 3.3%, 58.8 +/- 4.4%, and 82.7 +/- 2.5%, respectively). CONCLUSIONS: Taken together, this study demonstrates that megakaryocytic cells can be effectively produced ex vivo with as little as two-factors (SCF + PMP), an approach that might be favorably employed in a clinical expansion trial aiming to ameliorate high-dose chemotherapy-induced thrombocytopenia.

Cell Differentiation↗