Thin endometrium after radiation therapy as an unresolved treatment challenge: a case report.

Receptive endometrium is essential for successful implantation and ongoing pregnancy. Significant health issues and associated therapies, especially oncologic therapies, have potential to negatively impact future fertility in young women. Irradiation and chemotherapeutic alkylating agents are known to cause ovarian failure in most females; however, less well is characterized the impact of irradiation on uterine development and integrity. With an increasing number of cancer survivors, women are seeking infertility treatment after such therapies. Here, we present a young woman who developed ovarian failure after the treatment of acute myeloid leukemia with bone marrow transplant and preceding irradiation and chemotherapy and who was diagnosed with thin endometrial lining while seeking infertility therapy.

Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.

Radioimmunotherapy (RIT) for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab) labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J) model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11) targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g) of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM) and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.

Patient-specific alpha-particle dosimetry.

Alpha-particle therapy has received increased attention during the last few years because of the development of new targeting constructs and new labeling techniques and the availability of suitable α-particle - emitting radionuclides. This work provides an overview of methods that have been used in clinical trials in estimating the absorbed dose to tumors and healthy tissue in patients following such α-particle therapy. Similarities and differences compared to conventional therapies using ߯-particle emitters are presented. The specific challenges of establishing accurate dosimetry for α- particles in the individual patient are also discussed, as is the effect that improved patient-specific dosimetry might have on the overall efficacy of this type of therapy.

Pretargeted radioimmunotherapy using anti-CD45 monoclonal antibodies to deliver radiation to murine hematolymphoid tissues and human myeloid leukemia.

Radioimmunotherapy (RIT) for treatment of hematologic malignancies frequently fails because of disease recurrence. We therefore conducted pretargeted (P)RIT studies to augment the efficacy in mice of therapy using a pretargeted anti-human (h)CD45 antibody (Ab)-streptavidin (SA) conjugate followed by a biotinylated clearing agent and radiolabeled 1,4,7,10-tetraazacylodode cane N,N',N",N'''-tetraacetic (DOTA)-biotin. Tumor-to-blood ratios at 24 hours were 20:1 using pretargeted anti-hCD45 RIT and <1:1 with conventional RIT. In vivo imaging studies confirmed that the PRIT approach provided high-contrast tumor images with minimal blood-pool activity, whereas directly labeled anti-hCD45 Ab produced distinct tumor images but the blood pool retained a large amount of labeled Ab for a prolonged time. Therapy experiments showed that (90)Y-DOTA-biotin significantly prolonged survival of mice treated with pretargeted anti-hCD45 Ab-SA compared with mice treated with conventional RIT using (90)Y-labeled anti-hCD45 Ab at 200 muCi. Because human CD45 antigens are confined to xenograft tumor cells in this model, and all murine tissues are devoid of hCD45 and will not bind anti-hCD45 Ab, we also compared one-step and PRIT using an anti-murine (m)CD45 Ab where the target antigen is present on normal hematopoietic tissues. After 24 h, 27.3% +/- 2.8% of the injected dose of activity was delivered per gram (% ID/g) of lymph node using (131)I-A20-Ab compared with 40.0 +/- 5.4% ID/g for pretargeted (111)In-DOTA-biotin. These data suggest that pretargeted methods for delivering RIT may be superior to conventional RIT when targeting CD45 for the treatment of leukemia and may allow for the intensification of therapy, while minimizing toxicities.

[Comparison of total body irradiation-cyclophosphamide versus busulphan-cyclophosphamide as conditioning regimens for myelogenous leukemia: a meta-analysis].

Total body irradiation combined with cyclophosphamide (TBI/CY) and busulphan combined with cyclophosphamide (BU/CY) are standard conditioning regimens in hematological stem cell transplantation for patients with myelogenous leukemia. This study was aimed to compare the therapeutic efficacy of TBI/CY and BU/CY as conditioning regiment for acute or chronic myelogenous leukemia. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CNKI, CBM (Chinese Bio-medicine Database) had been searched for all relevant articles (1999-2007). Comparative studies were carried out on clinical therapeutic effects of TBI/CY and BU/CY including stem cell engraftment, relapse, complications, transplant-related mortality, and disease-free survival. A meta-analysis was performed using Review Manager 4.2 software and funnel plot regression was adopted to assess the publication bias. The results indicated that 2149 articles in English and 46 articles in Chinese were got, and finally 9 clinical trials with total 3039 patients have been assessed. No significantly difference was found in engraftment failure and transplant-related mortality resulting from TBI/CY and BU/CY conditioning regimens, but the incidence of veno-occlusion of liver and hemorrhagic cystitis obviously increased in BU/CY group after transplantation, the acute GVHD, interstitial pneumonia and cataract significantly increased in TBI/CY group. The relapse rate of AML in TBI/CY group was lower than that in BU/CY group, and the rate of long-term disease-free survival of AML patients in TBI/CY group also significantly lower than that in BU/CY group, but the relapse rate of CML in TBI/CY group after transplantation was obviously higher than that in BU/CY group, but there was no difference in longterm disease-free survival rate between the two conditioning regimens mentioned above. It is concluded that the meta-analysis confirms different effects of TBI/CY and BU/CY regimens on myelogenous leukemia transplantation. This result is useful for physicians to select treatment regimens.

Nuclear localizing sequences promote nuclear translocation and enhance the radiotoxicity of the anti-CD33 monoclonal antibody HuM195 labeled with 111In in human myeloid leukemia cells.

UNLABELLED: Our objective was to evaluate the toxicity of the anti-CD33 monoclonal antibody HuM195 modified with peptides (CGYGPKKKRKVGG) harboring the nuclear localizing sequence (NLS; underlined) of simian virus 40 large T antigen and labeled with (111)In against acute myeloid leukemia (AML) cells. METHODS: HuM195 was derivatized with sulfosuccinimidyl-4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (sulfo-SMCC) to introduce maleimide groups for reaction with NLS-peptides and then conjugated with diethylenetriaminepentaacetic acid for labeling with (111)In. The immunoreactivity of NLS-HuM195 was evaluated by its ability to displace the binding of (111)In-HuM195 to HL-60 leukemia cells. Nuclear localization was measured in HL-60 cells by subcellular fractionation. The antiproliferative effects of (111)In-NLS-HuM195 and (111)In-HuM195 on HL-60, U937, or K562 cells with high, intermediate, or minimal CD33 expression, respectively, were studied. The survival of HL-60 cells or patient AML specimens treated with (111)In-NLS-HuM195 or (111)In-HuM195 was studied. Normal tissue toxicity was evaluated in BALB/c mice injected intravenously with of 3.7 MBq (22 microg) of (111)In-NLS-HuM195 or (111)In-HuM195. RESULTS: NLS-HuM195 exhibited relatively preserved CD33 binding affinity (dissociation constant [K(d)] = 4.3 +/- 1.7 x 10(-9) mol/L to 6.9 +/- 1.3 x 10(-9) mol/L). Nuclear uptake increased from 10.5% +/- 0.5% for (111)In-HuM195 to 28.5% +/- 4.1% or 65.9% +/- 1.5% for (111)In-HuM195 substituted with 4 or 8 NLS-peptides, respectively. The inhibitory concentrations of 50% (IC(50)) and 90% (IC(90)) for HL-60 cells treated with (111)In-NLS-HuM195 were 37 kBq per 10(3) cells and 77-81 kBq per 10(3) cells, respectively. The IC(50) and IC(90) values for (111)In-HuM195 were 92 kBq per 10(3) cells and 203 kBq per 10(3) cells. Growth inhibition was correlated with the level of CD33 expression. The survival of HL-60 cells was reduced from 232 +/- 22 colonies (control) to 7 +/- 1 colonies with 1.48 mBq per cell of (111)In-NLS-HuM195; no colonies were found at 3.33 mBq per cell. The surviving fraction decreased >2-fold in 7 of 9 AML specimens treated with an excess of (111)In-NLS-HuM195 and >10-fold in 2 of these specimens. There were no decreases in body weight or hematologic parameters or increases in alanine aminotransferase or creatinine in mice administered 3.7 MBq (22 microg) of (111)In-NLS-HuM195 or (111)In-HuM195. There was no morphologic damage to the liver or kidneys. CONCLUSION: We conclude that NLS-peptides routed (111)In-HuM195 to the nucleus of AML cells, where the emitted Auger electrons were lethal. (111)In-NLS-HuM195 is a promising targeted radiotherapeutic agent for AML.

Heart and muscle involvement by extra-medullary myeloid leukemia: a case report and review of the literature.

Extra-medullary myeloid tumours (EMT) have been described after curative treatment for acute myeloid leukaemia (AML) in increasing numbers after allogeneic stem cell transplantation. The sites of manifestations are ubiquitous and the discovery is most frequently guided by symptoms reported by the patient or by findings on clinical examination. This study reports a case of EMT in muscles and the heart 1.5 years after allogeneic transplantation for an AML with t(8;21)(q22;23) who achieved a complete remission by use of an idarubicine-based combination chemotherapy. Pathological and imaging findings are presented and treatment options are discussed.

Treatment of childhood acute myeloid leukemia.

Childhood acute myeloid leukemia is rare, but accounts for a significant number of malignancy-related deaths in this age group. However, the prognosis has improved over past decades, and survival rates of 60% and above have been reported. Still, this implies that more than a third of children and adolescents die from this disease. Moreover, treatment is intensive, and quality of life and late effects are worrying issues. Therefore, there is a need for further improved treatment of pediatric acute myeloid leukemia. This review describes several important developments in this respect, such as improved diagnostics, prognostic factors, subgroup-directed and tailored treatment, and targeted therapy. In addition, background information is provided and current treatment strategies are described, as well as the late effects of treatment. Most groups now have risk-group adapted protocols, with allogeneic stem cell transplantation often being reserved for the higher risk group. Even in these cases, the benefit of stem cell transplantation has not been demonstrated beyond reasonable doubt with current high-intensive chemotherapy. Similarly, the use of cranial irradiation for CNS prophylaxis and maintenance treatment does not seem to be indicated in general. Subgroup-directed treatment has become a reality for acute myeloid leukemia in young children with Down's syndrome and in acute promyelocytic leukemia. In addition to tailoring therapy according to biologic features and especially monitoring treatment by measurements of minimal residual disease, targeted therapy for subgroups with activating mutations in receptor tyrosine kinases will further optimize the treatment of pediatric acute myeloid leukemia. Together with the development of many novel agents that have different mechanisms of action than the currently available anticancer agents, and improved supportive care, it is realistic that the prognosis of acute myeloid leukemia in children and adolescents will improve further in the next 5-10 years.

Production of actinium-225 for alpha particle mediated radioimmunotherapy.

The initial clinical trials for treatment of acute myeloid leukemia have demonstrated the effectiveness of the alpha emitter (213)Bi in killing cancer cells. Bismuth-213 is obtained from a radionuclide generator system from decay of 10-days (225)Ac parent. Recent pre-clinical studies have also shown the potential application of both (213)Bi, and the (225)Ac parent radionuclide in a variety of cancer systems and targeted radiotherapy. This paper describes our five years of experience in production of (225)Ac in partial support of the on-going clinical trials. A four-step chemical process, consisting of both anion and cation exchange chromatography, is utilized for routine separation of carrier-free (225)Ac from a mixture of (228)Th, (229)Th and (232)Th. The separation of Ra and Ac from Th is achieved using the marcoporous anion exchange resin MP1 in 8M HNO(3) media. Two sequential MP1/NO(3) columns provide a separation factor of approximately 10(6) for Ra and Ac from Th. The separation of Ac from Ra is accomplished on a low cross-linking cation exchange resin AG50-X4 using 1.2M HNO(3) as eluant. Two sequential AG50/NO(3) columns provide a separation factor of approximately 10(2) for Ac from Ra. A 60-day processing schedule has been adopted in order to reduce the processing cost and to provide the highest levels of (225)Ac possible. Over an 8-week campaign, a total of approximately 100 mCi of (225)Ac (approximately 80% of the theoretical yield) is shipped in 5-6 batches, with the first batch typically consisting of approximately 50 mCi. After the initial separation and purification of Ac, the Ra pool is re-processed on a bi-weekly schedule or as needed to provide smaller batches of (225)Ac. The averaged radioisotopic purity of the (225)Ac was 99.6 +/- 0.7% with a (225)Ra content of < or =0.6%, and an average (229)Th content of (4(-4)(+5)) x 10(-5)%.

The incidence of testicular recurrence in boys with acute leukemia treated with total body and testicular irradiation and stem cell transplantation.

BACKGROUND: The incidence of testicular recurrence of childhood acute leukemia after total body irradiation (TBI) in conjunction with stem cell transplantation (SCT) has been reported to be as high as 24%. The authors studied the incidence of testicular failure in a large series of male patients who underwent SCT using either TBI and a testicular irradiation boost or chemotherapy alone. METHODS: One hundred thirty-one boys with either acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) were treated with SCT with either TBI with testicular boost (n = 94 patients), TBI without testicular boost (n = 1 patient), or chemotherapy alone (n = 36 patients) between 1991 and 1999. RESULTS: The median follow-up was 26.5 months (range, 0.6-99.5 months) from the date of bone marrow infusion. Two patients in the study had a primary testicular failure after TBI with testicular boost followed by an umbilical cord blood transplantation. The first patient had ALL, did not engraft, and was rescued with autologous cells. He developed disease in the testicle 15 months afterward and subsequently died. The second patient had Philadelphia chromosome-positive ALL and developed a testicular recurrence 26 months after SCT. He was treated with orchiectomy, further testicular irradiation, and chemotherapy and remained in complete remission > 3 year after his failure. The incidence of testicular failure in boys who received TBI and testicular irradiation who survived > or = 1 year was 4.2%. There were no primary testicular failures reported in boys who received chemotherapy alone. CONCLUSIONS: Boys with AML or ALL had a low incidence of primary testicular failure when they were treated with TBI plus a testicular boost or with chemotherapy alone.

Serum thyroglobulin as a marker of thyroid neoplasms after childhood cancer.

AIM: To evaluate serum thyroglobulin (Tg) level as a marker of the development of thyroid disease when following individuals who received neck irradiation therapy in childhood. METHODS: In a non-randomized cross-sectional study Tg was assessed in 172 survivors of childhood cancer 10.8 y (1.9-24) median (range) after diagnosis and 7.9 y (0.9-24.3) median (range) after the end of treatment. The patients were divided into two groups: group 1 included 47 patients who had received irradiation to the neck and group 2 included 125 patients who did not receive irradiation to the neck. RESULTS: Patients who had received irradiation to the neck had significantly higher Tg levels compared with those who did not receive neck irradiation: median 14.0 (1.0-189.0) microg/L vs median 8.8, (0.7-112.2) microg/L (p < 0.001). Six out of seven patients with elevated Tg levels (>70 microg/L) had received neck irradiation. Among these six patients, two patients developed secondary differentiated thyroid cancer and two patients developed benign thyroid neoplasms. None of the patients who had normal levels of Tg developed thyroid cancer. CONCLUSION: A high Tg level should be a cause for further investigation in the follow-up of individuals who have received irradiation therapy in childhood.

Myeloablative conditioning regimens for AML allografts: 30 years later.

During the last three decades, several myeloablative conditioning regimens have been used for AML allografts. In this review, we systematically examine the data from studies reporting on myeloablative conditioning regimens for AML allografts. High-dose busulfan combined with cyclophosphamide (BuCy) and cyclophosphamide in combination with total body irradiation (CyTBI) are the two most commonly used conditioning regimens for AML allografts. From the available data, there are no significant differences in survival with these two regimens. A small benefit of decreased relapse rate with CyTBI is counterbalanced by a nonsignificant increase in treatment-related mortality. The incidence of veno-occlusive disease is significantly higher in patients treated with BuCy. Therapeutic monitoring of busulfan was not reported in any of the studies comparing the regimens. Either of the regimens can be used for AML allografts, and the choice may ultimately depend on local availability and expertise. Further improvements may be possible from modifications of the standard regimens. Data from these latter studies seem to be encouraging, but are not based on comparative randomized trials.

Preclinical studies targeting normal and leukemic hematopoietic cells with Yttrium-90-labeled anti-CD45 antibody in vitro and in vivo in nude mice.

A study was undertaken to investigate the suitability of using a high affinity (Kd = 1.1 nM) anti-CD45 monoclonal antibody for delivering the high energy beta-particle emitting isotope (90)Y to lymphohematopoietic target cells in vivo. The antibody, AHN-12, recognized the tyrosine phosphatase CD45 expressed on the surface of normal and malignant hematopoietic cells and studies showed that it reacted with both CD45-expressing normal peripheral blood cells and leukemia cells from patients. The antibody was readily labeled with (90)Y using the highly stable chelate 1B4M-DTPA and the radioimmunoconjugate was designated (90)Y-anti-CD45. The agent selectively bound to CD45(+) B cell line Daudi, but not CD45(-) control cells and significantly (p = 0.007) more bound to Daudi tumors growing in athymic nude mice than did a control non-reactive antibody. Moreover, biodistribution data correlated well to an anti-Daudi effect observed against established tumors in nude mice. The effect was dose dependent and irreversible with the best results in mice receiving a single dose of 137 microCi (90)Y-anti-CD45. These mice displayed a significantly (p < 0.0095) better anti-tumor effect than a control (90)Y-labeled antibody and survived over 135 days with no evidence of tumor. Histology studies showed no significant injury to kidney, liver, or small intestine even at 254 microCi, the highest dose tested. Because radiolabeled anti-CD45 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data indicate that this agent may be used to improve treatment of hematopoietic malignancies, particularly leukemia and lymphoma, when combined with hematopoietic stem cell transplantation in a future clinical trial.

Thyroid neoplasms after therapeutic radiation for malignancies during childhood or adolescence.

BACKGROUND: Recent data indicate that the risk of developing a thyroid neoplasm clearly is increased after high-dose, therapeutic radiation therapy during childhood. To better understand the time course, natural history, and histopathology of thyroid lesions that develop after high-dose irradiation, the authors undertook a retrospective study of all survivors of childhood and adolescent malignancies who were treated at Memorial Sloan-Kettering Cancer Center and who developed a clinically apparent thyroid neoplasm. METHODS: The authors searched the data base of the Department of Pediatrics, the hospital-based tumor registry, and the hospital medical records database for patients with thyroid neoplasms. RESULTS: Thirty-three patients were identified who developed a thyroid neoplasm after therapeutic radiation. Primary diagnoses were Hodgkin disease (n = 18 patients), non-Hodgkin lymphoma (n = 10 patients), acute lymphoblastic leukemia (n = 2 patients), acute myeloid leukemia (n = 1 patient), Wilms tumor (n = 1 patient), and neuroblastoma (n = 1 patient). The median age at the time of diagnosis of the primary malignancy was 12.0 years (range, 3.7-18.3 years), the median radiation dose to the thyroid gland was 2400 centigrays (cGy; range, 1000-4200 cGy), and the median interval from the time of radiation therapy until the recognition of thyroid disease was 13.0 years (range, 6.2-30.1 years). Thirteen of 33 thyroid lesions (39%) were malignant (11 papillary carcinomas and 2 follicular carcinomas). Age at diagnosis, gender ratio, and time elapsed since initial treatment did not differ between patients with malignant and benign lesions, but the median radiation dose to the thyroid was lower in patients who had malignant disease compared with patients who had benign disease (2000 cGy vs. 2950 cGy; P = 0.03). Disease was confined to the neck in all patients who had malignant thyroid lesions; after a median follow-up of 6.5 years (range, 0.9-12 years), none of the patients developed progressive or recurrent disease. CONCLUSIONS: Data from this study suggest that a high proportion of clinically apparent thyroid neoplasms that develop after therapeutic radiation for a childhood malignancy are malignant. However, most of these thyroid malignancies do not appear to behave in an aggressive fashion. Because thyroid neoplasms may not become evident for decades after radiation therapy, all individuals who are at risk require life-long follow-up.

Exploring technical and cultural appeals in strategic risk communication: the Fernald radium case.

Risk disputes are often characterized by tensions between technical and cultural understandings of risk and by communication practices that reflect those differing perspectives. This study considers how participants in risk debates draw upon and combine aspects of technical and cultural rationality as broad orientations to risk in expressing their views and formulating persuasive appeals during risk debates. Rhetorical theorist Kenneth Burke's (1984) concept of frames of acceptance is used to analyze a case study involving competing priorities for radium stored at the Fernald site, a former Department of Energy nuclear weapons facility. A rhetorical analysis is conducted using the transcript from a 1995 public meeting during which local residents and a nuclear medicine expert discussed priorities of Fernald site cleanup versus providing radium stored on site for promising cancer research. Two tensions are identified that fostered disagreement among discussants: the first a tension between a local or global context for the controversy and the second a tension between competing definitions of public participation for this issue. This study analyzes the rhetorical strategies by which participants in the Fernald radium debate articulated these tensions and argues that technical and cultural rationality (Plough & Krimsky, 1987) acted as sources of rhetorical invention influencing participants' individual frames of acceptance and the ways they defined and interpreted the situation and crafted persuasive appeals.

Irradiation for conjunctival granulocytic sarcoma.

CASE HISTORY AND FINDINGS: A 73-year-old woman with a history of myeloproliferative syndrome (MPS) presented with bilateral chemosis, redness and burning of the eyes. The ocular motility was severely impaired. Ophthalmological examination revealed markedly distended conjunctivas on both sides. Biopsy disclosed conjunctival granulocytic sarcoma as an initial symptom of acute myelogenous leukemia (AML). Diagnosis was confirmed by peripheral blood smear and bone marrow aspiration. TREATMENT AND OUTCOME: The orbital tumor disappeared completely after local external beam irradiation with a total dose of 30 Gy and no further orbital recurrence occurred. With chemotherapy following irradiation transient hematological remission was achieved. 5 months after diagnosis the patient died of respiratory failure following atypical pneumonia as a consequence of her underlying disorder. CONCLUSION: Detection of orbital granulocytic sarcoma, even in the absence of typical leukemic symptoms is of practical importance, because treatment with irradiation can lead to stabilization or improvement in the patient's vision.

Targeted therapy of cancer with radiolabeled antibodies.

This review focuses on the use of radiolabeled antibodies in the therapy of cancer, termed radioimmunotherapy (RAIT). Basic problems concerning the choice of antibody and radionuclide and the physiology of tumor and host are discussed. Then follows a review of pertinent clinical publications on various radioantibody constructs in the treatment of hematopoietic and solid tumors of diverse histopathologies, grades, and stages, and in different clinical settings. Factors such as dose rate delivered, tumor size, and radiosensitivity play a major role in determining therapeutic response, while target-to-nontarget ratios and, particularly, circulating radioactivity to the bone marrow determine the major dose-limiting toxicities. RAIT appears to be gaining a place in the therapy of hematopoietic neoplasms, such as non-Hodgkin's lymphoma, with several agents advancing in clinical trials toward registration, of which one has just been approved by the FDA. Although RAIT of solid tumors has shown less progress, pretargeting strategies, such as an affinity-enhancement system consisting of bispecific antibodies separating targeting from delivery of the radiotherapeutic, appear to enhance tumor-to-nontumor ratios and may increase rad doses to tumor more selectively than directly labeled antibodies.

A case of generalised cutaneous granulocytic sarcoma in an elderly patient with myelodysplastic syndrome.

Granulocytic sarcoma is a rare extramedullary malignant mass composed of primitive cells of the granulocytic lineage. It can arise from any part of the body and is frequently associated with haematological diseases, commonly acute myeloid leukaemia. Rarely, it has been found in conjunction with myelodysplastic syndrome. We report a case of cutaneous granulocytic sarcoma in a 73-year-old lady. The patient presented with a two-month history of multiple skin nodules which were confirmed by skin biopsy to be granulocytic sarcoma. Bone marrow examination was consistent with myelodysplastic syndrome. Localised radiotherapy to the skin lesions were given. She died from septicaemia six months after presentation. The management of this condition presents a diagnostic and therapeutic dilemma for both the pathologist and physician. In cases which are poorly differentiated as in this case, histological diagnosis is particularly difficult. Its definitive diagnosis would then require the additional use of a broad panel of immunohistochemical and cytochemical stains.

In vitro testing of the leukaemia monoclonal antibody WM-53 labeled with alpha and beta emitting radioisotopes.

We report the preparation and testing of a new alpha emitting radio-immunoconjugate (RIC) against acute myeloid leukaemia (AML) using CD33 positive monoclonal antibody WM-53 (specific for HL-60 cell line). Using cyclic anhydride of diethylenetriaminepentacetic acid (cDTPAa) as chelator, antibody was labeled with 213Bi (alpha), 149Tb (alpha), 153Sm (beta) and 152Tb (positron). In vitro testing showed high labeling efficiency (90-95%) and stability (11-19% leaching) with immunoreactivity virtually the same before and after labeling. DNA synthesis data and MTS cell survival were compared for all RICs. Only the alpha emitter was found to be capable of inhibiting DNA synthesis and had selective cell kill with activity as low as 2-3 microCi. The high stability and outstanding cytotoxicity of the 213Bi conjugate provides the basis for targeted alpha therapy for the control of metastatic and disseminated cancer such as AML.