Polarisation signals: a new currency for communication.

Most polarisation vision studies reveal elegant examples of how animals, mainly the invertebrates, use polarised light cues for navigation, course-control or habitat selection. Within the past two decades it has been recognised that polarised light, reflected, blocked or transmitted by some animal and plant tissues, may also provide signals that are received or sent between or within species. Much as animals use colour and colour signalling in behaviour and survival, other species additionally make use of polarisation signalling, or indeed may rely on polarisation-based signals instead. It is possible that the degree (or percentage) of polarisation provides a more reliable currency of information than the angle or orientation of the polarised light electric vector (e-vector). Alternatively, signals with specific e-vector angles may be important for some behaviours. Mixed messages, making use of polarisation and colour signals, also exist. While our knowledge of the physics of polarised reflections and sensory systems has increased, the observational and behavioural biology side of the story needs more (and more careful) attention. This Review aims to critically examine recent ideas and findings, and suggests ways forward to reveal the use of light that we cannot see.

Use of azathioprine for graft-vs-host disease is the major risk for development of secondary malignancies after haematopoietic stem cell transplantation: a nationwide population-based study.

BACKGROUND: As more patients are treated by haematopoietic stem cell transplantation (HSCT), development of secondary malignancy (SM) becomes an increasingly common issue in long-term survivors. METHODS: We conducted a nationwide population-based study of the Taiwanese population to analyse patients who received HSCT between January 1997 and December 2010. Standardised incidence ratios (SIRs) were used to compare the risk of SM in HSCT patients and the general population. Multivariate analysis was performed to identify independent predictors of SM. RESULTS: Patients receiving HSCT had a significantly greater risk of developing SM (SIR 2.00; 95% confidence interval (CI) 1.45-2.69; P<0.001). Specifically, the incidence increased for cancers of the oral cavity (SIR 14.18) and oesophagus (SIR 14.75) after allogeneic HSCT. Multivariate analysis revealed an increased SIR for cancer in patients who received the immunosuppressant azathioprine. The risk of SM also increased with greater cumulative doses of azathioprine. CONCLUSIONS: This study demonstrates an increased incidence of SM in Taiwanese patients who received allogeneic HSCT, especially for cancers of the oral cavity and oesophagus. This finding is different from results in populations of Western countries. Physicians should be cautious about azathioprine use for graft-vs-host disease after HSCT.

Increased cancer risk in patients with haemophilia A: a nationwide population-based 14-year study in Taiwan.

Haemostasis is associated with the development and dissemination of cancer. Whether cancer incidence is increased in haemophiliacs remains uncertain; thus, we aimed to further examine this issue. By using data from the National Health Insurance Research Database in Taiwan, we obtained a cohort of 683 patients with haemophilia A, and compared the incidence rate ratio (IRR) of cancer in this cohort with an age- and sex-matched control of 6830 patients. The log-rank test was used to compare Kaplan-Meier curve of the cumulative cancer incidence between two cohorts. Cox regressions were used to identify independent risk factors of cancer in the study patients. The cancer incidence of patients with haemophilia A was significantly higher compared to the control group (IRR 1.95, 95% CI 1.18-3.09, P = 0.008) during the 14-year follow-up period. The non-lymphoma and non-liver cancer incidence in the haemophilia A cohort remained higher than that of the matched control (P = 0.050 by the log-rank test). The multivariate Cox proportional hazards analysis indicated that age (per year, HR 1.09, 95% CI 1.06-1.12, P < 0.001) was the only significant risk factor for cancer development in haemophilia patients. Patients with haemophilia A had higher cancer incidence than the age- and sex-matched patients, especially for the elderly. With increasing life expectancy for haemophiliacs, physicians should be aware of their cancer development.

Adult T-cell leukaemia/lymphoma can mimic other lymphomas in a non-endemic area: dilemmas in diagnosis and treatment.

BACKGROUND: The diagnosis of Adult T-cell leukaemia/lymphoma (ATL) in non-endemic regions is challenging. AIM: This study analyses the clinicopathologic features and diagnostic processes of ATL patients in Taiwan. METHODS: ATL patients diagnosed and treated at Taipei Veterans General Hospital from 1998 through 2010 were retrospectively identified. The diagnosis of ATL was confirmed by in situ detection of human T-cell leukaemia virus type 1 (HTLV-1) when necessary. Patients' data were reviewed and analysed. RESULTS: Fourteen ATL patients were identified, among whom six (42.9%) had an antecedent diagnosis of other malignant lymphomas before the ATL diagnosis, including two diagnosed with Hodgkin disease (HD), one with peripheral T-cell lymphoma, two with chronic lymphocytic leukaemia and one with angioimmunoblastic T-cell lymphoma. Of the 14 patients, eight (57%) were subclassified as the acute type, three (21.4%) as the lymphoma type, and three (21.4%) as the chronic type ATL. Five of six (83.3%) patients with initial non-ATL misdiagnosis were diagnosed with non-acute type ATL. In particular, a patient with an antecedent diagnosis of HD presented with typical Reed-Sternberg (RS)-like cells harbouring Epstein-Barr virus genomes in affected lymph nodes. The patient progressed to acute type ATL 3 years after the initial diagnosis, and HTLV-1 genomes were identified in the previous RS-like cells. CONCLUSION: In non-endemic areas, such as Taiwan, ATL, particularly the non-acute type, may mimic other lymphomas and easily be misdiagnosed. HTLV-1 serology should be routinely screened in all malignant lymphoma patients. In situ detection of HTLV-1 is helpful in cases with diagnostic dilemmas.

Interleukin 10 and residual kidney function are associated with risk of vascular calcification in patients undergoing peritoneal dialysis.

AIMS: Vascular calcification is a common complication among dialysis patients and its pathogenesis involves a variety of factors. The roles of pro-inflammatory cytokines and residual kidney function (RKF) in peritoneal dialysis (PD) patients with vascular calcification have not been investigated. MATERIALS AND METHODS: 157 stable PD patients were enrolled. All patients had plain X-ray film examination including chest (posterior-anterior view, CXR) and pelvis. Vascular calcification was interpreted as calcified deposit over aortic arch and linear calcification of pelvic arteries. Relevant biochemical data, pro-inflammatory markers, and PD-related factors were measured and collected. RESULTS: Vascular calcification prevalence in CXRs was higher than that in pelvis films (38.2% vs. 22.3%, p < 0.05). Patients with vascular calcification in CXR had higher incidence of calcification in pelvis films (p < 0.05). Only a minor portion (14.6%) had two calcification sites. Regression analysis revealed that age, PD duration, body mass index, and RKF were independent factors associated with vascular calcification in CXR. Age, diabetes, IL-10 and RKF were factors associated in pelvis films. Factors independently related to vascular calcification in both films were age, duration, diabetes, IL-10, and RKF. CONCLUSIONS: Besides traditional risk factors, IL-10 and RKF were important factors associated with vascular calcification in PD patients.

A new hospice consulting system for terminal cancer patients in transferring to post-acute care options in Taiwan.

The terminal cancer patients increase needs for hospice care day by day. A new hospice consulting system has been developed in Taiwan to provide options for terminal cancer patients in choosing a suitable post-acute hospice care while a combined hospice care system is also given by the consulting team in the acute wards. Hereinafter is our report. From March 2005 to January 2006, 313 terminal cancer patients were analysed. These patients had signed consent forms for palliative treatment and had received consultations from the new hospice consulting system. Multivariate analysis showed that the home care patients had better performance status (P = 0.012), less shortness of breath (P = 0.006), less limbs swelling (P = 0.043), less flatulency (P = 0.000) and less constipation (P = 0.018). Among the 162 patients with regular follow-up, the symptoms/signs were significantly improved after intervention of consulting team in pain (P = 0.000), shortness of breath (P = 0.000), difficulty in sleeping (P = 0.002), nausea (P = 0.004), constipation (P = 0.008), changes in skin (P = 0.024) and adoption (P = 0.000). This new system had significant improvement in the terminal cancer patients' symptoms/signs control in acute wards and could contribute to the care quality of home care patients.

Hepatitis B infection in haematopoietic stem cell transplantation: still unresolved.

Impact of hepatitis B virus (HBV) infection on haematopoietic stem cell transplantation (HSCT) was reported earlier since late 1980s. It was shown that changing patterns of HBV serological markers was accompanied by variable severity of hepatitis after transplantation. Recipient's hepatitis B virus surface antigen (HBsAg) positivity was not considered an absolute contra-indication to allogeneic HSCT. However, HBsAg positivity was an important risk factor of reactivation hepatitis after transplantation, especially in allogeneic setting. Managing HBV reactivation in HSCT recipients was not successful till the availability of lamivudine since mid-1990s. For HBsAg-positive recipients, prophylactic lamivudine has been shown to significantly reduce reactivation hepatitis. As for HBsAg-negative recipients, there have been a small number of patients who develop so-called reverse seroconversion, that is, appearance of HBsAg after transplantation. In addition to chronic graft-versus-host disease, the risk was also high in allogeneic HSCT recipients who received fludarabine-antithymocyte globulin-containing conditioning regimens. The HBV is harboured earlier in the recipients before transplantation rather than transmitted via transfusion. At present, the optimal duration of lamivudine prophylaxis is not well-defined, and there are several fatal cases associated with early withdrawal and resistant HBV mutants. In conclusion, in HBV-endemic areas, the war between HBV and HSCT recipients continued even though several anti-HBV agents and molecular detection techniques are available. It deserves additional effort to overcome and also presents a chance to elucidate underlying mechanisms of HBV immunity, which are not easily studied in non-HSCT setting.

Haematopoietic stem cell transplantation in Taiwan: past, present, and future.

In Taiwan, haematopoietic stem cell transplantation (HSCT) has been used to treat patients with haematological diseases since 1983. Thereafter till 2007, there were 2537 patients who had undergone HSCT in more than 15 hospitals. Their diseases included acute myeloid leukaemia in 27.8% of cases, non-Hodgkin's lymphoma 23.3%, acute lymphoblastic leukaemia 12.8%, chronic myeloid leukaemia 11.9%, severe aplastic anaemia 8.7%, and multiple myeloma 4.1%. Most of the cases received myeloablative conditioning regimens. More than 15% of cases received non-myeloablative regimens, and the mean age of these cases was at least 10 years older than those who received myeloablative regimens. The types of graft included peripheral blood (60.4%) and bone marrow (32.0%). A total of 35% of patients received autologous grafts. Of 1557 allogeneic HSCT patients, 338 (21.7%) received grafts from unrelated donors. Cord blood transplantation has been successfully performed in paediatric patients with thalassaemia major and with a large body size, and adult patients. The incidence of acute graft-versus-host disease was relatively low in Taiwan. On the contrary, a relatively higher proportion of hepatitis B carrier in the recipients had led to a higher incidence of reactivation hepatitis, which was markedly decreased following lamivudine prophylaxis. In conclusion, HSCT has become a routine therapy for major medical centres in Taiwan. Our unique experiences in the past decades also contributed to the progress of HSCT. With the establishment of professional association and patient supportive groups, we hope we can fully improve our daily practice and clinical as well as basic research in HSCT.

Current status of hematopoietic stem cell transplantation in Taiwan.

In Taiwan, hematopoietic SCT (HSCT) has been used to treat patients with hematological diseases since 1983. Since then, more than 2200 patients have undergone HSCT in 15 large hospitals. The disease entities included acute leukemia in 37% of cases, non-Hodgkin's lymphoma in 26%, CML in 10%, multiple myeloma in 7% and severe aplastic anemia in 6%. The conditioning regimens used were mainly myeloablative (84% of cases). Non-myeloablative regimens were fludarabine-based. The average age of allogeneic recipients was at least 10 years older than those in the era before their application. The grafts of all patients were derived from peripheral blood in 85% of cases, BM in 13% and cord blood (CB) in 2%. Forty percent of HSCT patients received autologous grafts, whereas more than 25% of allogeneic HSCT patients received grafts from unrelated donors, and overall, there were more than 200 Taiwan HSCT recipients. Currently, CB has been used successfully in pediatric patients with thalassemia major and also in adult patients with hematological malignancy. After transplantation, there was a relatively lower prevalence of acute GVHD. However, a relatively higher proportion of hepatitis B carriers in the recipients had led to a higher incidence of viral reactivation and clinical hepatitis, which was dramatically decreased following lamivudine prophylaxis. In conclusion, HSCT has been successfully adapted to routine clinical care in Taiwan. Several important findings contributing to the progress of HSCT in the past two decades have also been noticed on this island.

A program of cell death and extracellular matrix degradation is activated in the amnion before the onset of labor.

Fetal membranes usually rupture during the process of labor. Premature fetal membrane rupture occurs not infrequently and is associated with significant fetal and maternal morbidity. The mechanisms of normal and pathologic fetal membrane rupture are not well understood. We have examined structural and biochemical changes in the rat amnion as labor approaches in order to characterize this process in normal pregnancy. Here we report that before the onset of active labor the amnion epithelial cells undergo apoptotic cell death which encompasses degradation of 28S ribosomal subunit RNA and associated P proteins and fragmentation of nuclear DNA. Concurrent with these cellular changes, the amnion type I collagen matrix is degraded with the accumulation of three-quarter length type I collagen fragments in extraembryonic fluid, characteristic of the cleavage of fibrillar collagen by interstitial collagenase. Western blot and immunohistochemical analyses confirmed that interstitial collagenase protein appears in association with the loss of amnion type I collagen. We conclude that amnion epithelial cells undergo a process of programmed cell death associated with orchestrated extracellular matrix degradation which begins before the onset of active labor. Thus, fetal membrane rupture is likely to be the result of biochemical changes as well as physical forces.

Biodegradable interstitial release polymer loading a novel small molecule targeting Axl receptor tyrosine kinase and reducing brain tumour migration and invasion.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour. The neoplasms are difficult to resect entirely because of their highly infiltration property and leading to the tumour edge is unclear. Gliadel wafer has been used as an intracerebral drug delivery system to eliminate the residual tumour. However, because of its local low concentration and short diffusion distance, patient survival improves non-significantly. Axl is an essential regulator in cancer metastasis and patient survival. In this study, we developed a controlled-release polyanhydride polymer loading a novel small molecule, n-butylidenephthalide (BP), which is not only increasing local drug concentration and extending its diffusion distance but also reducing tumour invasion, mediated by reducing Axl expression. First, we determined that BP inhibited the expression of Axl in a dose- and time-dependent manner and reduced the migratory and invasive capabilities of GBM cells. In addition, BP downregulated matrix metalloproteinase activity, which is involved in cancer cell invasion. Furthermore, we demonstrated that BP regulated Axl via the extracellular signal-regulated kinases pathway. Epithelial-to-mesenchymal transition (EMT) is related to epithelial cells in the invasive migratory mesenchymal cells that underlie cancer progression; we demonstrated that BP reduced the expression of EMT-related genes. Furthermore, we used the overexpression of Axl in GBM cells to prove that Axl is a crucial target in the inhibition of GBM EMT, migration and invasion. In an in vivo study, we demonstrated that BP inhibited tumour growth and suppressed Axl expression in a dose-dependent manner according to a subcutaneous tumour model. Most importantly, in an intracranial tumour model with BP wafer in situ treatment, we demonstrated that the BP wafer not only significantly increased the survival rate but also decreased Axl expression, and inhibited tumour invasion. These results contribute to the development of a BP wafer for a novel therapeutic strategy for treating GBM invasion and increasing survival in clinical subjects.

Isovolemic hemodilution normalizes the prolonged passage of red cells and plasma through cerebral microvessels in the partially ischemic forebrain of rats.

The objective of this study was to determine whether hemodilution could normalize the mean transit times of red blood cells (Tr) and plasma (Tp) through cerebral microvessels in a partially ischemic brain. Wistar-Kyoto (WKY) rats, aged 30-40 weeks, were divided randomly into three groups. The first group was the nonocclusion, nonhemodilution (NN) normal control group. The second group was the occlusion, nonhemodilution (ON) group, in which animals were treated with bilateral carotid artery ligation. The third group was the occlusion-hemodilution (OH) group, in which animals were treated with bilateral common carotid artery ligation and, then, isovolemic hemodilution by replacing blood with the same volume of 3% modified fluid gelatin. Local cerebral blood flow (lCBF) and microvascular volumes of red blood cells (Vr) and plasma (Vp) in 14 brain structures were measured using 14C-iodoantipyrine, iron-55 labeled red blood cells, and 14C-inulin, respectively. The amount of oxygen delivered to local brain structures (OD), cerebral microvascular blood volume (Vb), mean transit time of blood (Tb), Tr, and Tp through cerebral microvessels were calculated from the data. Two hours after carotid artery ligation, lCBF decreased by approximately 38% in forebrain structures, 22% in rostral hindbrain areas, and 8% in the caudal hindbrain (29% for all 14 structures). The decreases in ODs were parallel with those of lCBFs, at 33, 17, and 2% in the three regions, respectively (24% for all structures). In contrast, Vb increased by 68, 37, and 16% in the three regions, respectively (48% for all structures). Tr and Tp were markedly prolonged (180% for Tr and 154% for Tp) in the forebrain regions, moderately (91% for Tr and 73% for Tp) in the rostral hindbrain, and mildly (60% for Tr and 13% for Tp) in the caudal hindbrain, with a mean increase of 136% for Tr and 111% for Tp in all structures. When data in the OH and NN groups were compared, lCBF values tended to be slightly higher and Vb values were significantly higher (p < 0.05) in the OH group. ODs in the eight forebrain structures were all significantly less (p < 0.05) in the OH group than the NN group. Tr and Tp values in the forebrain were similar between the OH and the NN groups. In conclusion, occlusion of the bilateral common carotid arteries in WKY rats causes partial forebrain ischemia, in which both Tr and Tp are prolonged. These prolongations of Tr and Tp can be normalized by isovolemic hemodilution. However, the ischemic forebrain remains hypoxic after hemodilution.

Fulminant hepatitis is significantly increased in hepatitis B carriers after allogeneic bone marrow transplantation.

BACKGROUND: Bone marrow transplantation (BMT) is effective treatment for many hematologic disease, but performed in a population with a high endemic hepatitis B virus carrier rate, the incidence of liver function impairment and fulminant hepatitis (FH) is expected to be raised. METHODS: Forty-three hepatitis B virus carriers received high-dose chemotherapy and BMT, 32 patients received an allogeneic graft, and 11 patients autologous marrow. Acute graft-versus-host disease prophylaxis consisted of methotrexate on day 1, 3, 6, and 11 and cyclosporine for 6 months. RESULTS: After a median follow-up period of 68 months (range: 1-11.5 years), 26 (81.3%) allogeneic BMT patients developed impaired liver function (LF), 5 progressed to FH on day 93, 169, 170, 180, and 468, respectively, and died after an average of 13.8 days (range: 1-45 days). Whereas only 4 (36.4%) autologous BMT patients developed impaired LF, and none FH. Impaired LF (P=0.026, chi-square), and FH (odds ratio=12.86, P=0.009 for coefficient) were significantly related to an allogeneic marrow graft, and the timing of liver function impairment coincided with cyclosporine withdrawal. Hepatitis B surface antigen (HbsAg) disappeared from the serum in 4/14 (28.6%) patients receiving a marrow graft from an HbsAg+ donor. HbsAg was not detected in the serum after BMT in 2/11 (18.2%) autologous BMT patients. CONCLUSIONS: Hepatitis B virus carriers receiving a marrow graft from an HbsAg+ donor have a significantly increased risk of FH.

Study of bone marrow cells in non-Hodgkin's lymphoma by DNA analysis.

Using Southern-blot analysis, we studied samples of bone marrow (BM) cells from 73 patients with non-Hodgkin's lymphoma (NHL) in various clinical status. The frequency of gene rearrangement was disease-status dependent with a frequency of 65.8% at the diagnostic stage, 81.8% after relapse and 33.3% upon complete remission (CR). BM involvement was evident in a substantial portion of patients with untreated and relapsed lymphoma. The significance of BM involvement by DNA hybridization in relation to conventional clinical staging and histological grade was studied. By Southern-blot analysis, BM involvement was found in 76% of the patients at clinical stages (CS) I-III. The incidence of BM involvement in low, intermediate and high grades of NHL (Working Formulation) was 57%(4/7), 67%(22/33), and 89%(8/9) respectively. A comparative study of conventional BM biopsy vs DNA hybridization in a group of 47 NHL patients showed that all 12 patients (100%) with morphological BM involvement and 25 out of 35 patients (71%) with morphologically normal BM had clonal rearrangements of immunoglobulin (Ig), heavy chain and/or light chain; or T-cell receptor beta chain (TCR beta) genes in BM cells. The false negative rate in conventional BM biopsy was 53%(25/47). Southern-blot analysis on lymph nodes (LN) and BM cells from 37 patients showed that 6 patients (16%) had cross-lineage or different rearranged patterns in the same or different tissues. Southern-blot analysis was found to be highly reliable for the detection of even minimal populations of lymphoma cells in the BM and therefore should be the diagnostic choice for clinical staging of lymphoma.

Screening of anti-HTLV antibody in sera of normal individuals and patients with malignancies in Taiwan.

In the present study an immunofluorescence using KH-2 cells as target cells, has been developed for the screening of 1200 serum samples from normal individuals and 450 of cases from patients with various malignancies. The positive anti-HTLV-I antibody rate in the former group is 0.083% (1/1200) and while in the latter it is found to be 1.8% (8/450) (including 3 adult T-cell leukemia/lymphoma cases of the 92 hematopoietic and 5 of 358 non-hematopoietic malignancies). The differences between the two groups are found to be significantly different (p value is less than 0.0001). In addition to the 3 adult T-cell leukemia/lymphoma cases, the 5 seropositive cancer patients are of 5 different diseases. We have searched for the adult T-cell leukemia virus antigen and the p19 core protein in lymphoid cells of seropositive persons and the only positive cases were from cells of two proven adult T-cell leukemia (ATL) patients. Our results suggest that Taiwan is not an endemic area of adult T-cell leukemia virus and that KH-2 cells may be used for the detection of anti-HTLV-I antibodies.

Nonmyeloablative allogeneic bone marrow transplantation for orbital granulocytic sarcoma associated with t(8;21)(q22;q22) in acute myeloid leukemia.

We report a nonmyeloablative allogeneic bone marrow transplant (allo-BMT) from an HLA-matched unrelated donor in a case of acute myeloid leukemia (AML), M2 with t(8;21)(q22;q22) and the presence of orbital granulocytic sarcoma (GS), who had residual tumor after conventional chemotherapy. The course of BMT was well tolerated, with no major procedure-related toxicity. The residual orbital GS regressed completely 4 months after BMT. She is currently 19 months post BMT, disease-free. To our knowledge, this is the first reported pediatric patient with AML, GS and t(8;21)(q22;q22) who received a nonmyeloablative allo-BMT.

Liver disease in patients with liver dysfunction prior to bone marrow transplantation.

Twenty-two patients with previous hepatic compromise who underwent allogeneic bone marrow transplant (BMT) for treatment of hematologic malignancy or other hematologic disease between 1984 and 1990 were chosen for the present study. After transplant, 19 (86.4%) of the patients developed hepatitis, including six cases (27.3%) of acute hepatitis, 12 (54.6%) of chronic hepatitis and one uncharacterized hepatitis. Nine chronic hepatitis patients were followed-up for 7-56.5 months (medium 35.5 months) with biochemistry studies and ultrasonography. Throughout the observation period, liver cirrhosis or hepatoma were not detected and no patients developed veno-occlusive disease. Furthermore patients who developed hepatitis after transplant had worse prognoses. Based on serial serological survey of the various hepatitis B virus (HBV) antigens and antibodies, we have found that most of the recurrent viral hepatitis in transplant patients could be attributed to the reactivation of the virus. In addition, the use of immunosuppressive drugs, persisting infection by HCV and the development of graft-versus-host disease may also play a role in modulating the course of viral hepatitis in BMT patients.

Relapse of Graves' disease after successful allogeneic bone marrow transplantation.

As shown in many reports, allogeneic BMT can help cure autoimmune diseases. Conversely, we present a 24-year-old woman with Graves' disease, which was diagnosed just before BMT for CML. The Graves' disease remitted immediately after BMT but relapsed 18 months later. Since the donor was free from thyroid diseases and the patient showed a rapid shift to complete donor chimerism after BMT, the autoimmune problem seemed neither to arise directly from the donor nor simply from the recipient's residual lymphocytes. On the contrary, it was most likely compounded by chronic GVHD as suggested by the accompanying GVHD symptoms and the absolute donor karyotype in bone marrow cells. A Graves' disease-susceptible HLA allele was also shared between recipient and donor, possibly enhancing the chances of this condition developing. Thus, allogeneic BMT may facilitate relapses in autoimmune diseases as well as alleviating them.

CY/TBI-800 as a pretransplant regimen for allogeneic bone marrow transplantation for severe aplastic anemia using HLA-haploidentical family donors.

Allogeneic BMT is the treatment of choice for patients with SAA who have an HLA-identical sibling donor. The results, however, have been relatively poor for transplants from partially matched family donors or unrelated donors because of the high incidence of graft rejection and/or GVHD. Six multiply transfused patients received a novel conditioning regimen of CY 200 mg/kg and TBI 800 cGy prior to receiving marrow from their HLA-haploidentical family donors. Three recipient-donor pairs were mismatched for one HLA locus, one for two loci and two for three loci. A combination of MTX and CsA was used for GVHD prophylaxis. Engraftment was noted in all six patients. Acute GVHD occurred in four patients, two each for grade I and II, respectively. One patient, who was ABO-compatible with her donor had delayed onset of pure red cell aplasia (PRCA) which completely recovered 6 months after additional immunotherapy with prednisolone. There were two deaths; both occurred while patients were on treatment for GVHD. One was from systemic fungemia and the other probably from cytomegalovirus interstitial pneumonitis (CMV-IP). Four patients (66.7%) have been alive and disease-free for more than 8.2, 27.3, 38.4 and 47.2 months after BMT, respectively. The results suggest that CY/TBI-800 may be a simple and effective conditioning regimen for SAA patients receiving BMT from family members other than HLA-identical siblings.

Successful pregnancy following very high-dose total body irradiation (1575 cGy) and bone marrow transplantation in a woman with acute myeloid leukemia.

A 22-year-old woman had a normal full-term delivery 6 years after a successful allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI) to a total of 1575 cGy in seven fractions (225 cGy x 7, at a dose rate of 3.5 cGy/min). Graft-versus-host disease prophylaxis was with methotrexate and cyclosporin A. Grade I acute GVHD developed after BMT but there was no chronic GVHD. She became amenorrhoeic after BMT and serial gonadal testing indicated hypergonadotrophic hypogonadism. She became pregnant and delivered a full-term, healthy baby 6 years after BMT. Successful pregnancy after TBI of more than 1200 cGy is extremely rare. This case, to the best of our knowledge, is the second patient who received a higher dose of TBI (1575 cGy) to have a successful pregnancy. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 1200 cGy.