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Terminal deletions of chromosome 6q are rare. The clinical findings are variable and most often include growth restriction, craniofacial anomalies, dysmorphism, microcephaly, cardiac anomalies, genitourinary anomalies, seizures, and tone abnormalities. Clinical manifestations are essentially due to differences in size and location of chromosomal deletions. This condition is usually associated with life-threatening morbidities often presented very early in neonatal period. Antenatal detailed ultrasound can help in identifying the condition which could then be confirmed by microarray after amniocentesis.Here, we report a case of 6q deletion associated with facial, skeletal, and brain anomalies in a male preterm neonate. Our case shows many features that have hitherto not been observed in the reported cases worldwide. By reporting this case we intend to expand the already known database of information on the phenotypic features associated with 6q deletion syndrome.

Array antennas play an important role in different communication systems. In the synthesis of array antennas, different important parameters like pattern shape, side lobe level reduction, placement of nulls, and beam width are to be considered. Array antenna synthesis is done on different types of antennas to generate different shaped beams for practical applications. Optimization methods like the Quasi Newton method (QNM), particle swarm optimization (PSO) and Firefly optimization (FF) are used in determining different shaped patterns. In array synthesis as the number of elements increases the pattern converges to that of the desired pattern with the square of the difference approaching zero. QNM reduces the error function in very less number of iterations for the generation of stair step and Ramp shape patterns, when compared with PSO and Firefly algorithms in all array configurations. When the number of elements in the linear array is 80, 100, 200 Firefly has better performance than the PSO algorithm. The height of ripples reduced as the number of elements increases for both Ramp pattern and stair step pattern. Convergence plots for all array configurations are plotted and error values for each iteration for all elements are measured.

Long-term survival rates of patients with acute myelogenous leukemia treated with intensive chemotherapy are 15-20%, despite efforts to develop new treatment strategies. Murine M195 [(I-M195.sup.131)], an anti-CD33, immunoglobulin (Ig) G2a monoclonal antibody has reactivity restricted to early myeloid cells and myeloid leukemic blasts but not hematopoietic progenitors. Previous trials in patients with relapsed or refractory myeloid leukemia showed that [(I-M195.sup.131)] rapidly targeted to the bone marrow and internalized into target cells. This article describes a therapeutic dose escalation study in which 24 patients received from 50 MCI/M2 to 210 mCi/[m.sup.2] of [(I-M195.sup.131)] in divided doses. Cytoreduction of peripheral cell counts and bone marrow blasts occurred without nonhematopoietic toxicity. Doses [(I-M195.sup.131)] greater than 135 mCi/[m.sup.2] were associated with marrow cytoreduction sufficient to necessitate bone marrow transplant. However, 37% of the patients developed human anti-mouse antibody, preventing retreatment. To decrease immunogenicity and improve effector function, chimeric IgG1 and IgG3, and complementarity-determining region-grafted, humanized Iggi and Igg3 versions of mouse M195 were developed by genetic engineering techniques. The new versions maintained speciIficity and biologic function, and they were superior to the mouse M195 in their ability to perform antibody-dependent cellular cytotoxicity against leukemia cells. Humanized M195, but not chimeric M195, showed a 4-8.6 times higher avidity than its mouse counterpart. Because effector function of IgG depends to a large extent on Fc clustering, a homodimeric HuG1 also was developed. Homodimeric HuG1 showed an ability to cause additional dramatic improvements in effector functions, as well as an ability to internalize and retain radioisotope in target leukemia cells. Monomeric and dimeric forms of humanized M195 may be advantageous in the therapy of acute myelogenous leukemia.

The role of radioimmunodetection in the detection of cancer has been established through the development of high affinity immunoconjugates and recent improvements in radiochemistry. Advances in imaging techniques, particularly single-photon emission computed tomography and image registration, also have dramatically improved the sensitivity and accuracy of tumor detection. Molecular engineering of immune constructs provides promise of enhanced tumor localization properties and reduced immunogenicity, allowing repeated studies to be performed. The role of radioimmunodetection in the evaluation of cancer patients will increase in importance in the future.

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP+exosomes. Moreover, uptake of CEMIP+exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnfand Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.

The incidence of gynecological malignancies is on the rise partly because of the availability of screening programmes, awareness, higher technological advancements, and availability of better medical care. Early diagnosis of any malignancy leads to prompt treatment. Use of 18Fluorine-Fluorodeoxyglucose (18F-FDG) PET/CT in the treatment and follow-up of patients with Ca cervix considerably improves patient management. The primary diagnosis of Ca cervix is made either by biopsy of a visible tumor on the cervix or by a cone biopsy of a nonvisible malignant cervical focus. The staging procedure is purely clinical (i.e. gynecologic examination under general anesthesia) according to the International Federation of Gynaecology and Obstetrics classification. Earlier, with the nonavailability of sophisticated medical equipment and imaging specialists, oncologists relied heavily on clinical examination. However, anatomical and functional imaging has been proven to be considerably superior in understanding parametrial involvement and nodal/distant metastases in the cancer cervix than clinical examination alone. Data are evolving on the usage of 18F-FDG PET/CT in initial staging, treatment planning, and monitoring therapy response for gynecological malignancies. Prognostic information derived from the primary lesion such as the maximum standardized uptake value, metabolic tumor volume, and extent of para-aortic nodal metastatic disease plays a critical role in tailoring therapy on the basis of patient tumor-specific factors rather than on International Federation of Gynaecology and Obstetrics stage alone. Thus, 18F-FDG PET/CT needs to be listed not only under the panel of pretherapy investigations for Ca cervix but also for recurrence and therapy response assessments. It allows a more confident approach to patient management at initial staging, especially in terms of the decision to choose surgical versus palliation measures.

•Semi-automated 18F-FDG PET image analysis may aid measuring MM treatment response.•Semi-automated and reader-driven PET image analyses agreed in most SULpeakscans.•Semi-automated pipeline findings are predictive of MRD assessment by NGS.

Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0–8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8–20), RUNX1+FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20–28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGFβ and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders.

Combined heart-kidney transplantation (CHKT) is a therapy for a carefully selected subgroup of patients with concomitant heart and kidney failure. Discerning whether there is reversible or irreversible kidney disease is crucial to selection for CHKT versusheart transplant alone to optimize therapeutic value and organ allocation. Methods for determining extent of kidney disease include estimating glomerular filtration rate, creatinine clearance, kidney ultrasonography, and kidney biopsy. Additionally, the use of extracorporeal membrane oxygenation (ECMO) in the setting of CHKT only recently emerged as feasible. We present a case of a 69-year-old man with cardiogenic shock who was placed on venoarterial-ECMO (VA-ECMO) following orthotopic heart transplant (OHT) due to severe mediastinal bleeding and remained on VA-ECMO during kidney transplant. To our knowledge, this is the second report of a patient undergoing kidney transplant while on VA-ECMO following OHT.

Background: Stethorini are specialized mite predators in the family Coccinellidae, which are small with black body and brown or yellow colored appendages. This study aimed to survey species of Stethorini associated with phytophagous mites of South India and their prey range. Results: Eight species of Stethorini, viz., Parastethorussp. Stethorus(Allostethorus) forficatus, S. (A.) pauperculus, S. (A.) tetranychi, S. (A.) sp., S. keralicus, S. (S.) raniand S. (S.) sp., each associated with distinct species of mite were identified in this study and part of mitochondrial cytochrome c oxidase subunit I sequences of seven of these species are provided. Barcode gap analysis and distance summary analysis in the BOLD system as well as phylogenetic analysis of these seven species were given. Conclusions: This study revealed the species of Stethorini in South India along with their prey range and associated plants. As all the species look similar with black body and yellow appendages, DNA barcodes generated can be used as an effective bio-identification tool for this group.

This study is an attempt at achieving diesel fuel equivalent performance from diesel engines with maximum substitution of diesel with renewable fuels. In this context the study has been designed to analyze the influence of B20 algae biodiesel as a pilot fuel in a biodiesel biogas dual fuel engine, and results are compared to those of biodiesel and diesel operation at identical engine settings. Experiments were performed at various loads from 0 to 100 % of maximum load at a constant speed of 1500 rpm. In general, B20 algae biodiesel is compatible with diesel in terms of performance and combustion characteristics. Dual fuel mode operation displays lower thermal efficiency and higher fuel consumption than for other fuel modes of the test run across the range of engine loads. Dual fuel mode displayed lower emissions of NOxand Smoke opacity while HC and CO concentrations were considerably higher as compared to other fuels. In dual fuel mode peak pressure and heat release rate were slightly higher compared to diesel and biodiesel mode of operation for all engine loads.

Tumor endothelial marker 1 (TEM1, endosialin) is a tumor vascular marker with significant diagnostic and therapeutic potential. However, in vivo small animal models to test affinity reagents specifically targeted to human (h)TEM1 are limited. We describe a new mouse tumor model where tumor vascular endothelial cells express hTEM1 protein.Methods: Immortalized murine endothelial cells MS1 were engineered to express hTEM1 and firefly luciferase and were inoculated in nude mice either alone, to form hemangioma-like endothelial grafts, or admixed with ID8 ovarian tumor cells, to form chimeric endothelial-tumor cell grafts. MORAb-004, a monoclonal humanized IgG1antibody specifically recognizing human TEM1 was evaluated for targeted theranostic applications, i.e., for its ability to affect vascular grafts expressing hTEM1 as well as being a tool for molecular positron emission tomography (PET) imaging.Results: Naked MORAb-004 treatment of mice bearing angioma grafts or chimeric endothelial-tumor grafts significantly suppressed the ability of hTEM1-positive endothelial cells, but not control endothelial cells, to form grafts and dramatically suppressed local angiogenesis. In addition, highly efficient radioiodination of MORAb-004 did not impair its affinity for hTEM1, and [124I]-MORAb-004-PET enabled non-invasive visualization of tumors enriched with hTEM1-positive, but not hTEM1 negative vasculature with high degree of specificity and sensitivity.Conclusion: The development of a new robust endothelial graft model expressing human tumor vascular proteins will help accelerate the development of novel theranostics targeting the tumor vasculature, which exhibit affinity specifically to human targets but not their murine counterparts. Our results also demonstrate the theranostic potential of MORAb-004 as PET imaging tracer and naked antibody therapy for TEM1-positive tumor.

In this study a multiaxial isokinetic dynamometer was used to measure strength during various upper-body isokinetic exertions. Ten male participants performed 7 different upper-body isokinetic exertions. In addition, to evaluate the effect of speed on strength, each participant performed sitting pull exertions at the speed of 0.026, 0.130, and 0.260 m/s. Average isokinetic strength increased from 236.6 ± 39.1 to 291.8 ± 65.8 N with the initial increase in speed from 0.026 to 0.130 m/s. The average isokinetic strength decreased to 276.7 ± 87.2 N with a further increase in speed to 0.260 m/s. The curve between isokinetic strength and speed followed a bell-shaped curve (fitted with the Gaussian function, R2= .9). The results of this study could be useful in deciding on the work pace of various manual material handling tasks requiring maximal and/or near maximal exertions.

Unlike β particle–emitting isotopes, α emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the β-emitters 131I and 90Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of β-emitting constructs, the α-emitting isotope 213Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg 213Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the 213Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with β-emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of 213Bi-HuM195, and it is the first proof-of-concept for systemic targeted α particle immunotherapy in humans.

Bone marrow toxicity is generally dose-limiting for radioimmunotherapy (RIT) with β-emitting radionuclides. Treatment may be prescribed on the basis of administered activity or absorbed dose. An optimal definition of maximum tolerated dose will enable the clinical benefits of RIT to be maximized.Methods: We examined data from six clinical studies of RIT with various 131-I labeled antibodies and antibody fragments that treated a total of 114 patients. We also examined a sub-set of 36 patients with minimal prior chemotherapy who were treated with 131I-labeled intact murine IgG at a single institution. For both these groups the ability of absorbed dose-based methods to predict bone marrow tolerance was compared with that of activity-based methods.Results: Marrow toxicity was more accurately predicted by absorbed dose than by activity in the general case where a variety of different antibodies and antibody fragments were used. For the more homogeneous smaller group, well defined "dose-response" relationships were observed for both absorbed dose and administered activity. However, absorbed dose-based definitions of maximally tolerated dose yielded a better stratification of patients than activity-based definitions (including per meter squared) such that fewer patients had major toxicity when treated below "tolerance", and fewer patients had minor toxicity when treated above "tolerance".Conclusions: Absorbed dose-based definitions of maximum tolerated dose and escalation variables are optimal for 131I-labeled antibody therapy. The ability of pre-therapy dosimetry studies to predict the behavior of therapeutic administrations must be validated for prospective clinical applications.

We performed a prospective study to evaluate the imaging potential of thallium-201 as compared with other imaging modalities in differentiating residual/re-current tumors from post-therapy changes in patients with musculoskeletal sarcomas.201TI scans, magnetic resonance imaging (17), X-ray computed tomography (6) or contrast angiography (6) studies in 29 patients previously treated for musculoskeletal sarcomas were correlated with either histopathologic findings (26 patients) or 2-year clinical follow-up (three patients). All imaging studies were acquired within 2 weeks. Ratios of201T1 tumor uptake to the contralateral (28 patients) or adjacent region of interest were calculated. When qualitative interpretation was in doubt, only those cases with a ratio of 1.5 or more were considered suggestive of recurrent or residual viable tumor tissue. Residual or recurrent tumor tissue was verified in 21 patients by biopsy. All had true-positive201Tl scans while the other imaging modalities were true-positive in 20 and equivocal in one. In eight patients, there was no evidence of viable tumor tissue as proven by biopsy in five and long-term clinical follow-up in three.201Tl scan was false-positive (ratio 1.5) in one patient and true-negative in seven while the other' imaging modalities had four false-positives. The average201T1 ratios were 3.8±1.1 in the true-positive cases and 1.3±0.3 in the true-negative cases. The percentage sensitivities, specificities, and accuracy for201T1 were 100%, 87.5%, and 96.5% versus 95%, 50%, and 82.7% respectively for other imaging modalities These results indicate that201T1 scintigraphy is more accurate than other imaging modalities in differentiating residual/recurrent musculoskeletal sarcomas from post-therapy changes.

This trial studied the biodistribution, pharmacology, toxicity, immunogenicity, and biologic characteristics of a trace-labeled, anti-CD33, humanized monoclonal antibody M195 (Hu-M195) in patients with relapsed and refractory myeloid leukemia. Hu-M195 is a computer-modeled, “complementarity-determining region-grafted,” lgG1, humanized version of M195. M195 is a murine monoclonal antibody that reacts with CD33, a 67-kD glycoprotein expressed on early myeloid progenitor cells and myeloid leukemia (acute myelogenous leukemia and chronic myelogenous leukemia) cells, but not normal stem cells. 131I-murine-M195 has already shown significant ability to cytoreduce patients with relapsed or refractory myeloid leukemias. Hu-M195 has higher avidity than the original mouse monoclonal antibody and, unlike murine M195, has the capability to mediate antibody-dependent cellular cytotoxicity against leukemia targets. Thirteen patients with relapsed or refractory myelogenous leukemia were treated with Hu-M195 at 4 levels of 0.5, 1.0, 3.0, and 10.0 mg/m2in a phase I trial. Patients received a total of 6 doses per patient over 18 days. Two patients were retreated for a total of 12 doses. The first dose of Hu-M195 was trace-labeled with 131I to allow detailed pharmacokinetic and biodistribution studies by serial sampling of blood, radioimmunoassays of cells, and whole-body gamma-camera imaging. Cumulative total doses of up to 216 mg of Hu-M195 were administered safely. Reversible fever and rigors were observed after infusion at the highest dose levels. The entire bone marrow was specifically and clearly imaged within hours after infusion, with optimal biodistribution occurring at the 3 mg/m2level. Adsorption of Hu-M195 onto targets in vivo was demonstrated by flow cytometry; near saturation of available sites occurred at the 3 mg/m2dose level. Plasma and whole body half lives were 38 and 51 hours, respectively, which may reflect continual replenishment of target sites on new leukemia cells. 131I-Hu-M195 was rapidly internalized into the target cells in vivo within 1 hour. Human antihuman antibody responses were not observed. In conclusion, Hu-M195 can be administered safely in multiple doses, without significant toxicity or any evidence of immunogenicity, and can localize rapidly and efficiently to the bone marrow in patients with myeloid leukemias. Additional phase II trials with this agent alone or in combination with cytokines or isotopes are warranted at the optimal biologic dose.

Nuclear medicine techniques have a long history in pulmonary medicine, one that has been continually changing and growing. Even longstanding methods, such as perfusion scanning for embolic disease or for pretherapy pulmonary function evaluation, have largely withstood the test of recent careful scrutiny. Not only have these techniques remained an important part of the diagnostic armamentarium, but we have learned how to use them more effectively. Furthermore, because of technical advances, we are in a phase of expanding roles for nuclear imaging. Gallium citrate scanning for the mediastinal staging and follow-up of lymphoma has been recognized as a valuable adjunct to the anatomic information provided by CT and MRI. With the growth of PET technology in areas that have been explored in a limited fashion until now, such as noncardiogenic pulmonary edema and lung carcinoma, evaluation and management of these patients may substantially improve. Finally, in the field of radiolabeled monoclonal antibodies, attention is now being turned to both the diagnostic and the therapeutic problems presented by lung carcinoma. As radiolabeling methods are refined and as new and better antibodies are developed, radioimmunodetection and therapy in lung carcinoma may begin to make inroads on this common and hard to control disease.

No relevant conflicts of interest to declare.

(Abstracted from Fertil Steril2016;105:364–368)In the last few decades as result of increasing obesity in the general population, greater numbers of obese women present to clinics for assisted reproduction Several studies examining autologous cycles have demonstrated detrimental effects of body mass index (BMI) on in vitro fertilization (IVF) outcomes. The mechanism of these adverse effects is unclear.

The ETS family of transcription factors is known to play an essential role in hematopoietic and vascular development. One such factor that is widely expressed in all vascular beds and almost all hematopoietic lineages, extending from long term hematopoietic stem cells to terminally differentiated peripheral blood cells, is Fli1. Global deletion of Fli1 leads to embryonic lethality at E12.5 due to dramatic hemorrhaging caused by poor vascular integrity and platelet dysfunction. The role of Fli1 in adults has been explored in several different cells types ranging from megakaryocytes to B and T cells. It has also been implicated in transcriptional regulation of hematopoietic stem and progenitor cells through combinatorial analysis, however its exact contribution to stem cell maintenance and function remains unclear. We hypothesized that Fli1 plays a dual role in regulating both the seed and the soil - specifically hematopoietic stem cell (HSC) function in a cell autonomous manner as well as the niche required for nurturing these cells. In this study, we focused our attention on the cell autonomous function of Fli1. We found that global deletion of Fli1 leads to lethality as a result of complete peripheral blood failure in addition to aberrant vasculature. Using the cre-lox system and various transplantation strategies, we identify Fli1 as one of the critical regulators of adult hematopoietic stem cell function. Specific deletion of Fli1 in the hematopoietic compartment alone is sufficient to induce significant reduction in peripheral blood counts, accompanied by hemorrhage, resulting in lethality. On further inspection, Fli1-/-HSCs are unable to expand ex vivo or engraft in a competitive setting. Additionally, Fli1 is essential for hematopoietic reconstitution post radiation and its deletion abolishes the ability of stem cells to reconstitute the bone marrow and contribute to peripheral blood lineages. ChIP-seq analysis demonstrates Fli1 occupancy in almost all essential hematopoietic gene enhancers and promoters. By correlating Fli1-/-HSC RNA seq analysis with the ChIP occupancy data we can conclude that Fli1 is, in fact, one of the master regulators of the HSC transcriptional program essential to maintain the balance between self-renewal and differentiation. Taken together, our results indicate that Fli1 is required for maintenance of HSC homeostasis and function, making it one of the unique transcription factors to play a critical role in HSC function in adults as well as during development.

No relevant conflicts of interest to declare.

HuM195, a humanized anti-CD33 monoclonal antibody, targets myeloid leukemia cells and has activity against minimal residual disease. To enhance the potency of native HuM195 and avoid nonspecific cytotoxicity seen with β-emitting radioimmunoconjugates, the α-emitting radiometal 213Bi was conjugated to HuM195. The feasibility, safety, and antileukemic activity of therapy with 213Bi-HuM195 were shown in a phase I trial (Jurcic et al. Blood 2002). Because of the short-range (50–80 μm) and high linear energy transfer (8400 keV) of α particles, radioimmunotherapy with 213Bi is ideally suited for the treatment of residual disease. To determine the effects of 213Bi-HuM195 after partial cytoreduction with chemotherapy, we treated 25 patients (median age, 67 years; range, 49–80) with cytarabine 200 mg/m2/day for 5 days followed by 213Bi-HuM195 in a phase I/II trial. Fourteen patients had relapsed or primary refractory AML; 5 patients had previously untreated de novoAML, and 6 patients had untreated secondary AML. Sixteen patients had intermediate-risk cytogenetics, and 9 had poor-risk cytogenetics. During the phase I portion of the study, cohorts of 3–6 patients were treated with 0.5, 0.75, 1, and 1.25 mCi/kg. At the 1.25 mCi/kg dose level, 2 of the 4 patients had dose-limiting myelosuppression (grade 4 leukopenia lasting ≥ 35 days) and 1 patient died of progressive pneumonia. Therefore, the maximum tolerated dose was determined to be 1 mCi/kg. No responses were seen at the first two dose levels. Seven of the 19 patients (37%) who received 1 mCi/kg (n=15) or 1.25 mCi/kg (n=4) responded. There were 2 CRs lasting 9 and 12 months; 3 CRp (CR with incomplete platelet recovery) lasting 1, 2, and 6 months and 2 PRs lasting 3 and 8 months. The median time from initiation of chemotherapy to recovery of leukocyte counts was 34 days (range, 21–59 days). Delayed count recovery was attributed to persistent leukemia in 6 patients. Neutropenic fever occurred in all patients, and 19 patients had documented infections. At the phase II dose level, two of the 15 patients died of progressive infections, and one had grade 4 hyperbilirubinemia. The most common extramedullary toxicities were transient, low-grade elevations in liver function tests (n=19) and serum creatinine (n=11). Thirteen patients had infusion-related reactions following the first injection of 213Bi-HuM195, typically characterized by reversible grade 1 or 2 fever and/or chills. One patient had orthostatic hypotension and syncope after the first antibody infusion associated with concomitant bacteremia. Sequential administration of cytarabine and 213Bi-HuM195 is tolerable and can produce complete remissions in patients with AML.