Sandmaier software

Microfluidic platforms have been constructed for microbial extraction and have been combined with several analytical methods to detect pathogenic microorganisms [ 83 ]. For instance, a microfluidic chip can capture airborne pathogens. By converting the laminar flow to a twisted airflow inside the device, the contact probability between the channel wall and the bacteria in the airflow is increased. Hence, the microfluidic platform can collect hundreds of bacteria within a couple of microliters of aqueous media, which is sufficient for direct immune analysis or nucleic acid analysis.

However, this technique cannot work as itself, but it facilitates sampling and downstream bioanalysis [ 84 ].

Another substance that can be detected within microfluidic devices is creatinine. Its concentration is important in the determination of conditions like kidney failure, muscular dystrophy, and diabetic nephropathy. An example of this application was proposed by Narimani et al. The device requires polyvinylpyrrolidone-coated silver nanoparticles and polyvinyl alcohol-coated silver nanoparticles, as different concentrations of creatinine will create color differentiations when mixed with the synthesized solution.

The color changes were measured by capturing images in a designed isolated box with a uniformly illuminated imaging environment. MATLAB software applications allow real-time image processing, and the results are comparable with those from spectroscopic-based methods. Point-of-care technologies can be used for the detection of hormones as well [ 86 ].

The most common example is represented by the paper-based microfluidics within home pregnancy tests. Their working principle is the detection of human chorionic gonadotropin hormone, a glycoprotein that starts increasing its concentration in urine after a missed menstrual period [ 87 , 88 ]. Nowadays, these tests are advanced enough that they can not only sense the presence of hormones in urine, but they can also quantify it. To monitor hydration and manage health disorders, Choi et al.

Their soft, skin-compatible, multimodal microfluidic device presented integrated color reference markers that provided accurate colorimetric estimates of analyte concentrations under different lighting conditions and in remote settings. Amit Jadhav et al. Such constructions can successfully trap viruses from various biological fluids. Therefore, viruses may be accurately identified from their Raman signatures. However, this device is still in the prototype phase, and further investigations are required.

Just like the identification of pathogens or disease markers, DNA analyses can be performed on-chip to diagnose genetic-based diseases [ 34 ]. By controlling the reaction conditions and by introducing primers and other PCR reagents into the microfluidic platform, it can function as a point-of-care device for rapid and accurate analyses [ 83 ].

In this context, the use of microfluidic digital PCR has been employed for the detection of fetal chromosomal aneuploidy.

Fan et al. Le Roux et al. The analysis comprises a unique enzymatic liquid preparation of the DNA, microliter noncontact PCR, and a high-resolution separation. The proposed microfluidic chip is completely self-contained, meaning that, after sample input, no other liquids can enter or exit the microchip during the assay.

Moreover, the instrument itself is not directly in contact with any liquid. Therefore, the risk of contamination is minimized. Microfluidic devices for human identification are of great use also in forensics.

COC chips can be employed for DNA amplification and the testing of samples in a simple, quick, and relatively sensitive manner. The best results can be acquired with sample quantities of less than one milligram or with a pure substance, and the result can be observed with the unaided eye [ 37 ]. Moreover, the DNA extraction chip can be coupled with an expert profile-interpretation software that allows law enforcement agencies to check whether there is a match between a person under custody and the DNA profiles recovered from unsolved crime cases [ 94 ].

Since cells cultured in Petri dishes and tissue culture flasks undergo completely different environmental cues in comparison with natural tissues within a complex 3D ECM, miniaturized culture systems became a promising alternative [ 95 ]. Through accurately controlled fluid flows, microfluidic platforms can ensure relevant biochemical and biophysical cues to cultured cells in a well-defined and reproducible manner [ 96 ].

Therefore, it is possible to study tissue growth, renewal, and disease without difficulties specific to in vivo studies [ 95 ]. There is an increasing interest in developing microfluidic organs or tissues-on-a-chip, mainly due to two reasons: humans cannot be experimented on directly, and animal models may not mimic human physiology.

Moreover, such devices may reduce investments and shorten the time for drug discovery and drug testing. Space and effort needed for animal testing are eliminated by the usage of organs-on-a-chip that can run in parallel on a single platform [ 81 ].

By lining up several such chips, each with different types of cells, the whole-body response can be replicated [ 79 ]. Organ-level functions can already be reproduced in microfluidic devices made of clear polymers with hollow microchannels containing cells [ 79 ]. Lung-on-a-chip devices are highly useful for examining the toxicity of several nanoparticles and understanding the pulmonary diseases that can result from the blockage of small air paths [ 98 ].

Heart-on-a-chip is also a viable modeling possibility, allowing the analysis of contractility and electrophysiological behaviors in vitro. Besides, cardiac tissue contractility quantification can be performed under conditions of health, disease, and even exposure to chemical agents [ 98 ]. Liver-on-a-chip platforms can mimic in vivo conditions by recapitulating the sinusoidal structure of this organ, maintaining high cell viability and cellular phenotypes, and emulating the functions of native tissues [ 16 ].

In this respect, several models have been developed and are available for studying liver disease progression, facilitating drug discovery, and enabling toxicity tests [ 99 ]. For instance, Lee et al. The researchers provided the device with vascular and biliary channels to enhance liver functionalities in the chip. Gut-on-a-chip microfluidic devices have also been developed [ 97 ], with one example offered by Baydoun et al.

Gut-on-a-chip microfluidic device. Reprinted from an open-access source [ ]. Kidney-on-a-chip platforms have also attracted significant attention in the field of microfluidics, imitating the real renal tubular cell environment [ ].

Yin et al. The researchers reported a better performance compared with cells cultured in Petri dishes, both in terms of cell growth and drug nephrotoxicity evaluation, rendering the device useful for preclinical studies. Kidney-on-a-chip microfluidic device.

Bone-marrow-on-a-chip is another microfluidic application that can lead to a better understanding of the lineage, commitment, and self-renewal of hematopoietic stem cells. Moreover, such models have the capacity to produce hematopoietic and immune cells in vitro, functioning as biosynthesis devices for generating various therapeutic agents.

Furthermore, the bone marrow relation to radiation therapy allows the application of these tools in simulating and alleviating radiation-induced toxicity as well [ 15 ]. Even brain-on-a-chip models can be created to improve the in vitro drug evaluation process. These instruments hold the potential for creating a uniform profile of the controlled flow of nutrients, establishing individual cellular activity and providing a platform for the monitoring and excitation of neuronal cells.

Besides, mechanical, physiological, pharmacological, and biochemical aspects can be studied in real-time through this technology [ 36 ]. Blood-brain barrier BBB replication on a microfluidic chip is also possible and highly useful. BBB-on-a-chip mimics the structure and complexity of the native BBB, allowing the investigation of central nervous system diseases [ 98 ].

Other opportunities for organs-on-a-chip involve the potential combinations between them to study complex mechanisms in disease and drug screening [ 38 ]. Tian et al. The authors used this multiorgan-on-a-chip to model the organotropism of breast cancer extracellular vesicles, obtaining similar results compared with animal models.

These platforms are especially useful for drug testing and minimizing screening costs [ 81 , 98 ]. Moreover, by integrating these replicas of the tumor environment with different physiological modules, including the vasculature, cancer-on-a-chip models can further explore the interactions between cancer and other organs [ 15 ].

The enormous potential of microfluidic devices has also become a great interest in the development of drug delivery systems [ 28 , ]. The advantages of such microfluidic delivery systems are the precise dosage, targeted delivery, sustained and controlled drug release, the possibility of multiple dosing, and the appearance of only slight side effects [ 79 ].

There are three main types of microfluidic delivery systems—namely, drug carrier-free microfluidic systems, drug carrier-integrated microfluidic lab-on-a-chip systems, and microneedle-based drug delivery systems [ ]. Each class of devices may have subcategories, as presented in Figure 6. Microfluidic drug delivery systems classifications.

Created based on information from a literature reference [ ]. One example of a carrier-free microfluidic system was offered by Kim et al. The researchers designed, fabricated, and tested a microfluidic intracochlear delivery system with a reservoir and active dose control.

This approach resulted in a zero-net volume of liquid transfer while enabling the mass transport of compounds to the cochlea through diffusion and mixing. The system included a planar micropump to generate reciprocating flow and a drug reservoir a long microchannel connected in a series with a micropump and parallel with the reciprocating flow network.

The integrated device was tested on guinea pigs, leading to good results in terms of the safety and efficacy of the delivery. The authors were confident of the future use of their implantable cochlear drug delivery system for human clinical applications. A carrier-integrated microfluidic chip was proposed by Gianella et al. Their device could carry hydrophobic materials and could be used as a theranostic tool for simultaneous imaging-guided drug delivery in cancers.

This two-fold goal could be achieved due to the oil-in-water nanoemulsions that could carry iron oxide nanocrystals for magnetic resonance imaging, fluorescent dye Cy7 for near-infrared fluorescence imaging, and hydrophobic glucocorticoid prednisolone acetate valerate for therapeutic purposes. Microneedle systems are another good example of drug delivery via microfluidics [ 79 ].

Microneedles are minimally invasive devices that can access the microcirculation of the skin and deliver drugs through transdermal routes [ ]. One such example was represented by biodegradable composite microneedles based on calcium sulfate and gelatin for the transdermal delivery of insulin created by Yu et al.

The researchers reported less insertion pain and faster onset and offset of insulin pharmacokinetics in the body than for traditional subcutaneous administration. Moreover, the insulin released from the biodegradable microneedles had an effective hypoglycemic effect for a longer time compared with the subcutaneous injection route, holding great potential for diabetes treatment. It is undeniable that the development of nanotechnology has revolutionized many aspects of modern medicine, especially in the fields of biosensors, diagnostics, targeted drug delivery, and therapeutics [ , , ].

Numerous nanotechnology-based pharmaceutical products have already been approved for clinical use, while many others are at different stages of preclinical development [ , ]. Microfluidic devices are excellent synthesis platforms for a wide range of nanoparticles, which, due to their narrow size distribution, uniform shape, improved reproducibility, and high encapsulation efficiency, can further serve in a plethora of applications [ 8 , 79 ].

Due to their unique physicochemical properties, such as a higher contrast or higher brightness than conventional small-molecule agents, nanoparticles synthesized in microfluidic devices are promising materials for fluorescence, magnetic resonance, and ultrasound imaging [ 8 , 97 ].

An example of materials appealing for nanomedicine is represented by iron oxide nanoparticles, which can be used as diagnostic and therapeutic agents against human disease.

These non-toxic and biodegradable particles can act as contrast agents in magnetic resonance imaging or fluorescence imaging, drug carriers for small-molecule delivery, transfection vectors for gene therapy, and enhancers for magnetic hyperthermia [ 27 ].

Moreover, superparamagnetic iron particles can be employed in the on-demand release of active ingredients by magnetic positioning and exposure to an external stimulus, e. Microfluidic reactors can also be employed to produce radioisotopes required in positron emission tomography PET , a noninvasive medical diagnostic based on the intravenous injection of a drug with a known biological activity labeled with a positron-emitting nuclide.

The most widely used drug of this sort is 2-[ 18 F]-fluorodeoxy-D-glucose FDG , which is normally produced in batch processes in quantities sufficient for multiple doses from a single production run.

However, FDG production is quite a complicated task, combining automation with computer science and involving specialized equipment, high costs, timescale planning, and personnel exposure. These challenges can be overcome by synthesizing FDG in microfluidic devices. Besides the general advantages of microfluidic synthesis over batch processes, in this case, it should also be mentioned that this technology is compatible with the dose-on-demand approach, allowing the production of a single dose of a tracer when a single PET scan is needed, with the possibility to restart synthesis whenever a new dose is required as well.

As the reaction, purification, formulation, and quality control are all performed on a single small, disposable chip, the environmental impact is also reduced [ , , ]. The delicate control of nano-synthesis achievable with microfluidic methods also allows for obtaining nanoparticles with higher sensing capacities and broader detection ranges than bulk materials.

These properties serve well for creating biosensors [ 8 ]. One such material is polydiacetylene PDA , which has a unique, naked eye-observable color switch and fluorescence enhancement in response to various external stimuli, e. The interesting structural, spectral, and optical properties of PDA are considered only for self-assembled particles with controllable and uniform sizes. Other microfluidic synthesis products that can be used as biosensors are Au nanoparticles.

Zheng et al. In the first mixing channel of the chip, nanoparticles modified with capture antibodies, polystyrene microspheres modified with detection antibodies, and catalases are employed in the reaction with the target bacteria.

Then, hydrogen peroxide is injected and catalyzed on the nanoparticle—bacteria—polystyrene complexes, which are captured in a separation chamber. After this, the mixture of Au nanoparticles and crosslinking agents is injected to react with the catalysate in the second mixing channel and is incubated in the detection chamber.

There, Au nanoparticles aggregate, leading to a color changes from blue to red, which are is detected using the Hue—Saturation—Lightness-based imaging app on Android smartphones. Depending on this color, the concentration of the target bacteria is determined. Microfluidics synthesis is also appealing for the pharmaceutical industry, as it allows the production of cheaper, more effective, and more accessible drug formulations [ , ].

Active pharmaceutical ingredients APIs that result from highly exothermic reactions can be obtained in microreactors, as is the case of nitroglycerin, an active agent used for acute cardiac infarction [ ]. The enhanced control over the reaction, coupled with the quality of the products, convinced several pharmaceutical companies to implement microfluidic technology, especially for hazardous exothermic power-intensive syntheses [ , ].

Moreover, microfluidic devices are a valuable instrument for the encapsulation of water-soluble drugs in lipid nanoparticles in an effort to create more efficient drug formulations. In this respect, Hibino et al. The researchers obtained homogeneously distributed, small-sized CoQ 10 -MITO-Porters that were efficiently internalized into cells and accumulated in the mitochondria.

Other APIs reportedly produced within microfluidics are ibuprofen [ ], lactose [ ], aspirin [ ], indomethacin [ ], danazol [ ], cefuroxime axetil [ ], piroxicam [ ], piracetam [ ], carbamazepine [ ], and more. In addition, microreactors have been successfully employed in the fabrication of biodegradable polymer-based nanocarriers. One such example is poly lactic-co-glycolic acid copolymer PLGA , a macromolecular compound approved by the Food and Drug Administration FDA that can be used for the synthesis of drug-loaded nanoparticles via a flow-focusing method in microchannels [ ].

Chiesa et al. The biocompatibility and biodegradability of these chosen polymers, together with precise control over the nanoparticle properties achieved through microfluidic fabrication, improved the in vivo biodistribution performances and N-Ac pharmacokinetic profile after administration. Other biodegradable polymers that have attracted research interest towards microfluidic production are poloxamer, chitosan, hyaluronic acid, alginate, and polyvinylpyridine-b-poly ethylene oxide [ , , ].

Much interest has also been drawn to the microfluidic platform synthesis of liposomes, as they represent highly efficient drug delivery systems [ ]. Liposomal carriers achieve selective and sufficiently precise localization of the diseased site, also ensuring a slow and sustained release [ , ], the features required for the treatment of cancers and inflammatory conditions [ ], infections, meningitis, malaria, HIV, hepatitis A, and influenza [ ].

Liposomes of well-controlled sizes can encapsulate small molecules, such as amphotericin B and doxorubicin [ ], being proposed to deliver vaccines, anticancer drugs, and gene therapy [ ]. Solid lipid nanoparticles SLNs have also been widely evaluated as alternative drug delivery systems due to the possibility of a prolonged drug release and enhanced stability of the nanoparticle system.

Producing SNLs by microfluidic methods results in superior properties in terms of size, polydispersity, and morphology compared to SNLs synthesized in bulk [ ]. Niosomes represent a less-researched, yet equally promising, drug delivery platform.

These nonionic surfactant-based vesicles can be prepared in microfluidic chips and be further used in food, cosmetic, and pharmaceutical applications [ ]. In this respect, Ag Seleci et al. Another sector in great need of microfluidic-produced nanoparticles is theranostics, an emerging field concerning the combination of diagnosis and treatment abilities into a single agent.

Theranostics is especially useful for tackling cancer challenges. In this field, microfluidic systems contributed through their capability of multistep flow control to forming multifunctional nanoparticles bearing therapeutic and diagnostic agents with higher drug encapsulations in comparison to the classic methods [ 8 , 28 , ].

An example of such particles is cancer cell membrane-coated nanoparticles, which consist of a nanoparticle core covered by a cancer cell plasma membrane coating that can carry tumor-specific receptors and antigens for cancer targeting. The core of these biomimetic nanoparticles can serve as a carrier for imaging and therapeutic moieties.

The major applications for which these particles are used in cancer are homologous targeting to deliver imaging and therapeutic agents, the disruption of cancer cell—stromal cell interactions, and the induction of an immune response.

However, some challenges and issues need to be solved before translating this therapeutic approach for use in humans [ ]. Furthermore, quantum dots obtained through microfluidic methods are capable of diagnosing and delivering molecules to cancer cells in vivo.

Through the control and maneuvering of reaction conditions in microfluidic synthesis, quantum dot functionality is increased, improving their sensitivity and ensuring the early detection of solid nodules or circulating tumor cell markers. As quantum dots hold great theranostic potential, academic research is moving towards clinical translation [ ]. Even though there are already many available applications, the development of microfluidics has just begun.

The existing technology can be further improved, devices can be even more miniaturized, chips can be integrated with various other devices, synthesis processes can be better controlled, new reaction pathways can be investigated, and novel applications may arise.

A kit of standardized stickers is packed in a toolbox, each sticker representing one component of the final microfluidic chip. The fabrication process is mobile, inexpensive, and time-saving, while the resultant microfluidic devices have well-defined features, ideal performances, and customizability [ 7 ].

A distinct field that has begun to develop is flexible microfluidics, a multifunctional and multidisciplinary field that ingeniously combines biology, electronics, chemistry, and medicine [ ]. The creation of flexible chips with reduced thicknesses and enhanced wear comfort opens the door for future use in smart contact lens sensors, the real-time noninvasive monitoring of physiological parameters, or tattoo-based sensors.

Such applications are attractive for assessing the health status of astronauts, being capable of estimating their blood sugar, kidney function, and liver activity without impacting the overall mass of the spaceship [ ]. Another area of opportunity for microfluidics is in pediatric patients or in patients suffering from conditions that make the sampling process difficult.

For instance, microfluidic devices may be used to perform the sweat chloride test needed in cystic fibrosis. This is advantageous because it only requires a small-volume sample, which is a really important aspect, as the possible sample volume is limited by the low sweat volume and evaporation [ ].

Another new and promising field has appeared at the convergence of microfluidics and ultrasounds. This combination is technically feasible, leading to synergistic results for drug encapsulation [ 3 ], diagnostics, and therapeutic applications [ ].

Moreover, microfluidics can be involved in studying blood cell deformability to provide vital information for the early diagnosis of blood-related diseases. Besides, blood analog fluids can be analyzed in microfluidic devices, with the aim of developing new treatments in a personalized medicine approach [ ].

Cells can not only be cultured and analyzed in microfluidic devices, but they can be created there as well. As these biomimetic materials can imitate cell behaviors and act as bioreactors for synthetic biology, this emerging technology has great potential for cell function research, biomaterial fabrication, and regenerative tissue engineering [ ]. Another synergistic convergence is the combined field of microfluidics and machine learning. Nowadays, most microfluidic devices are operated manually, but it is possible to develop and integrate on-chip multimodal instrumentation.

In this way, autonomous platforms can be created, and the experimental data can be sent to machine learning for processing. Hence, instead of analyzing the results of the experiment after it is performed, machine learning allows the device to learn from the data and make accurate predictions to guide and optimize the conducted research. This intelligent microfluidics represents the next generation of platforms for drug discovery, nanomaterials, in vitro organ modeling, and developmental biology [ ].

Several other innovative combinations of microfluidics with new domains, such as artificial intelligence, metamaterials, and neuromorphic engineering, may bring about unprecedented technological advancements in the foreseeable future [ ].

To summarize, microfluidics technology represents an emerging multidisciplinary research field with extensive applications in various domains. The inexpensive, portable, and disposable nature of these chips makes them suitable for applications such as point-of-care devices, wearable biosensors, forensic tests, drug delivery systems, drug screening platforms, and microreactors for in situ preparations of various compounds. The wide range of materials that are accessible nowadays, combined with the numerous possibilities for processing them, result in countless alternatives for fabricating microfluidic chips.

By correlating and tailoring these two elements, it is possible to meet most if not all of the requirements coming from the market. Moreover, through a series of advancements in interconnected science fields, microfluidic devices have the potential to reach industrial-scale production.

To conclude, despite still being in its infancy, microfluidics has gained a lot of attention from researchers worldwide. Therefore, this field is expected to soon expand the knowledge of nanoparticle synthesis and nano- and biomedicine, pointing to disruptive applications that will solve some of the most pressing current healthcare problems. All authors have read and agreed to the published version of the manuscript.

National Center for Biotechnology Information , U. Int J Mol Sci. Published online Feb Find articles by Cristina Chircov. Author information Article notes Copyright and License information Disclaimer. Received Jan 28; Accepted Feb This article has been cited by other articles in PMC. Abstract Microfluidics is a relatively newly emerged field based on the combined principles of physics, chemistry, biology, fluid dynamics, microelectronics, and material science.

Keywords: microfluidic devices, fabrication techniques, chip materials, biomedical applications, drug delivery, organ-on-a-chip. Fabrication of Microfluidic Devices 2. Microfluidic Device Materials One of the fundamental steps in microfluidic applications is selecting the optimum material for device fabrication [ 11 ]. Table 1 Comparison of several available materials for the fabrication of microfluidic platforms.

Open in a separate window. Chip Fabrication Methods Microfluidics has come a long way in a relatively short time due to several technological advancements from various fields that have gained research interest and been adapted for chip production.

Figure 1. Table 2 The classification of microfluidic fabrication techniques. Chemical Processes Several chemical fabrication processes have been used for a long time for manufacturing glass and silicon microfluidic channels [ 10 , 19 ]. Mechanical Processes Micromachining was one of the first known methods for fabricating microfluidic devices, as it was borrowed from the pre-existing field of semiconductors [ 20 ]. Figure 2. Laser-Based Processes Generally, lasers are expensive tools, but compared to cleanroom facility costs, they are considered a more accessible fabrication technique [ 66 ].

Three-Dimensional printing Three-dimensional printing is a relatively new, yet successful approach to forming microfluidic channels [ 17 ]. Hybrid Technologies Hybrid technologies appeared as a solution to overcome the challenges and limitations of each stand-alone fabrication method. Applications of Microfluidic Devices Microfluidic devices can be used in a plethora of applications, seeking to overcome the difficulties or challenges in traditional assays.

Diagnosis Devices Microfluidic devices allow the analysis of various samples, such as blood, saliva, or cell tissues, to provide a rapid and accurate diagnosis [ 81 ] Figure 3. Figure 3. Cell Culture Media Since cells cultured in Petri dishes and tissue culture flasks undergo completely different environmental cues in comparison with natural tissues within a complex 3D ECM, miniaturized culture systems became a promising alternative [ 95 ].

Figure 4. Figure 5. Drug Delivery Systems The enormous potential of microfluidic devices has also become a great interest in the development of drug delivery systems [ 28 , ].

Figure 6. Nanomaterial Synthesis Platforms It is undeniable that the development of nanotechnology has revolutionized many aspects of modern medicine, especially in the fields of biosensors, diagnostics, targeted drug delivery, and therapeutics [ , , ]. Emerging and Future Applications Even though there are already many available applications, the development of microfluidics has just begun. Conclusions To summarize, microfluidics technology represents an emerging multidisciplinary research field with extensive applications in various domains.

Author Contributions A. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. References 1. Whitesides G. The origins and the future of microfluidics. Ren K. Materials for Microfluidic Chip Fabrication. Shrimal P. A review on novel methodologies for drug nanoparticle preparation: Microfluidic approach.

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Author information Copyright and License information Disclaimer. Corresponding author: George L. Copyright notice. The publisher's final edited version of this article is available at Biol Blood Marrow Transplant. See other articles in PMC that cite the published article. Abstract Background Disease relapse and toxicity are the shortcomings of reduced intensity conditioning RIC for allogeneic hematopoietic cell transplantation alloHCT.

Introduction Reduced intensity conditioning RIC regimens for allogeneic hematopoietic cell transplantation were developed based upon the hypothesis that hematologic malignancies could be controlled by allograft derived immunologic anti-tumor effects without intensive cytoreductive chemotherapy or radiation and their toxicities. Open in a separate window. Figure 1. Consort Diagram. Supportive care Acute graft-versus-host disease GvHD prophylaxis consisted of tacrolimus, methotrexate, and mycophenolate as previously described.

Results Patient and disease characteristics Patient demographics are presented in Table 1. Table 1. Patient demographics a. Table 2. Unadjusted univariate alloHCT outcomes. Figure 2. Transplant related mortality. Table 3. Table 4. Figure 3. Table 5. Table 6. Figure 4. Survival for patients not in complete remission upon allogeneic hematopoietic cell transplantation. Discussion Toxicity and disease relapse have been the shortcomings of RIC regimens. Acknowledgements We thank the patients who participated in this study and the BMT Program clinical team members for their contributions to this study.

Footnotes Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Low-dose total body irradiation TBI and fludarabine followed by hematopoietic cell transplantation HCT from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil MMF can induce durable complete chimerism and sustained remissions in patients with hematological diseases.

HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Cellular and clinical pharmacology of fludarabine. Clin Pharmacokinet. Fludarabine-mediated repair inhibition of cisplatin-induced DNA lesions in human chronic myelogenous leukemia-blast crisis K cells: induction of synergistic cytotoxicity independent of reversal of apoptosis resistance.

Mol Pharmacol. Fludarabine triphosphate inhibits nucleotide excision repair of cisplatin-induced DNA adducts in vitro. Cancer Res. Chemo-radiotherapy: radiosensitizing nucleoside analogues review. Oncol Rep. Bone Marrow Transplantation. TBI lung dose comparisons using bilateral and anteroposterior delivery techniques and tissue density corrections.

J Appl Clin Med Phys. Bone Marrow Transplant. Multi-centre validation of the prognostic value of the haematopoietic cell transplantation- specific comorbidity index among recipient of allogeneic haematopoietic cell transplantation. Br J Haematol. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Regimen-related toxicity in patients undergoing bone marrow transplantation.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Perspectives on cancer therapy-induced mucosal injury. Classification systems for chronic graft-versus-host disease. Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection.

A multiple testing procedure for clinical trials. Scandinavian Journal of Statistics. ISBN 3——0; Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure.

J Clin Oncol. Rinsho Ketsueki ; 53 — Conditioning regimen of melphalan, fludarabine and total body irradiation in unmanipulated HLA haploidentical stem cell transplantation based on feto-maternal tolerance. Intern Med. Total body irradiation, fludarabine, melphalan, and allogeneic hematopoietic stem cell transplantation for advanced pediatric hematologic malignancies.

Addition of low dose total body irradiation to fludarabine melphalan reduced intensity conditioning is feasible, tolerable, and may improve outcomes in patients with high-risk acute myeloid leukaemia and other high risk myeloid malignancies. Am J Hematol. Comparison of error rates in single-arm versus randomized phase II cancer clinical trials.

Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. Significant improvement in survival after unrelated donor hematopoietic cell transplantation in the recent era.

Support Center Support Center. External link. Please review our privacy policy. Median time from diagnosis to alloHCT, months range. Disease status prior to transplant. Prior hematopoietic cell transplant. Time to neutrophil engraftment, median range days. Time to platelet engraftment, m edian range days. Hepatic veno-occlusive disease.

Disease status at alloHCT. Progression Free Survival.