New Constraint on the Local Relic Neutrino Background Overdensity with the First KATRIN Data Runs.

We report on the direct search for cosmic relic neutrinos using data acquired during the first two science campaigns of the KATRIN experiment in 2019. Beta-decay electrons from a high-purity molecular tritium gas source are analyzed by a high-resolution MAC-E filter around the end point at 18.57 keV. The analysis is sensitive to a local relic neutrino overdensity ratio of η<9.7×10^{10}/α (1.1×10^{11}/α) at a 90% (95%) confidence level with α=1 (0.5) for Majorana (Dirac) neutrinos. A fit of the integrated electron spectrum over a narrow interval around the end point accounting for relic neutrino captures in the tritium source reveals no significant overdensity. This work improves the results obtained by the previous neutrino mass experiments at Los Alamos and Troitsk. We furthermore update the projected final sensitivity of the KATRIN experiment to η<1×10^{10}/α at 90% confidence level, by relying on updated operational conditions.

Bound on 3+1 Active-Sterile Neutrino Mixing from the First Four-Week Science Run of KATRIN.

We report on the light sterile neutrino search from the first four-week science run of the KATRIN experiment in 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are analyzed by a high-resolution MAC-E filter down to 40 eV below the endpoint at 18.57 keV. We consider the framework with three active neutrinos and one sterile neutrino. The analysis is sensitive to the mass, m_{4}, of the fourth mass state for m_{4}^{2}≲1000 eV^{2} and to active-to-sterile neutrino mixing down to |U_{e4}|^{2}≳2×10^{-2}. No significant spectral distortion is observed and exclusion bounds on the sterile mass and mixing are reported. These new limits supersede the Mainz results for m_{4}^{2}≲1000 eV^{2} and improve the Troitsk bound for m_{4}^{2}<30 eV^{2}. The reactor and gallium anomalies are constrained for 100<Δm_{41}^{2}<1000 eV^{2}.

Current technical surgical practice of emergency appendicectomy: a cross-sectional survey of surgical registrars in the UK.

INTRODUCTION: Appendicectomy remains one of the most commonly performed procedures in general surgery. The aim of this study was to explore variation in operative techniques of an appendicectomy among surgical registrars in England. MATERIALS AND METHODS: An anonymised survey was sent out to surgical registrars in the UK via email and social media. Subgroup analyses were performed comparing respondents based on their level of seniority and subspecialty background. RESULTS: A total of 168 respondents completed the survey, of whom 77.4% (130/168) were specialty trainees years 3-8 and 44.6% (75/168) were colorectal trainees. The majority (98.8%) preferred a laparoscopic approach to appendicectomy. Overall, 73.2% opted to use diathermy to divide an uninflamed mesoappendix. Half of the respondents (50%) preferentially used diathermy to control the appendicular artery, followed by 44% preferring use of metal or polymeric clips. The appendicular stump was most often secured with Endoloops (85.7%) when removing a macroscopically uninflamed appendix but less readily used in the visibly inflamed appendix (75.6%, p = 0.01). Colorectal and upper gastrointestinal registrars were more likely to use diathermy on the mucosa of the appendix stump compared with other subspecialties (p = 0.03). The majority (82.1%) of respondents extracted the appendix via a retrieval bag. Regarding skin closure, most respondents (69%) adopted absorbable subcuticular sutures. Preferential duration of postoperative antibiotic use following appendicectomy for complicated appendicitis varied among the respondents. CONCLUSION: There are similarities and differences across surgical registrars in terms of technical practice in appendicectomy, partially attributed to prior experience and training.

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9}) eV^{2}. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation.

Serotonin transporter polymorphisms predict response inhibition in healthy volunteers.

Serotoninergic transmission is reliably implicated in inhibitory control processes. The aim of this study was to test the hypothesis if serotonin transporter polymorphisms mediate inhibitory control in healthy people. 141 healthy subjects, carefully screened for previous and current psychopathology, were genotyped for the 5-HTTLPR and rs25531 polymorphisms. Inhibitory control was ascertained with the Stop Signal Task (SST) from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The triallelic gene model, reclassified and presented in a biallelic functional model, revealed a dose-dependent gene effect on SST performance with Individuals carrying the low expressive allele had inferior inhibitory control compared to high expressive carriers. This directly implicates serotonin transporter polymorphisms (5-HTTLPR plus rs25531) in response inhibition in healthy subjects.

Alefacept treatment for refractory chronic extensive GVHD.

Alefacept (Amevive) is an immunosuppressive dimeric fusion protein that is used for psoriasis control. We recently showed its effect in acute steroid-resistant/dependent GVHD. In this study, we describe the effect of alefacept treatment on chronic extensive GVHD (cGVHD). Twelve patients were included in this study; of these 8 (9 of 13 episodes) showed response. The median time to initial response was 2.25 weeks and the response was marked (n=3), moderate (n=2) or minimal (n=4). In two responding patients, the response was only temporary. Complications that appeared during treatment included infection, pericarditis and squamous cell carcinoma of the lip. All these events may be related to other drugs given simultaneously. With a 30-month median follow-up, 6 of 12 patients are alive, with all but one with stable or improved cGVHD. Six patients died because of GVHD progression, whereas none of the patients experienced relapse of the disease for which the transplantation was done. As reported earlier in psoriatic patients treated with alefacept, we found a consistent increase in the percentage of naive T cells as a consequence of treatment. In conclusion, alefacept is effective for the treatment of cGVHD, and dose and time intervals of treatment should be explored further.

Allogeneic stem cell transplantation from matched related and unrelated donors in thalassemia major patients using a reduced toxicity fludarabine-based regimen.

The only radical cure for thalassemia major patients today is the replacement of the defective hematopoietic system by allogeneic stem cell transplantation (allo-SCT). The major obstacles for the application of allo-SCT even from matched family members have been the transplant-related morbidity and mortality and graft failure that is usually associated with the recurrence of the thalassemia hematopoiesis. The outcome of allo-SCT from HLA-identical family donors is largely dependent on the age of the recipient as well as on pretransplant parameters reflecting the degree of organ damage from iron overload. In this study we report our experience of allo-SCT from matched related and unrelated donors, using a reduced toxicity conditioning consisting of fludarabine, busulfan or more recently busulfex and antithymocyte globulin, in a cohort of 20 patients with thalassemia major. The regimen-related toxicity was minimal, while the incidence of acute grade II-IV and chronic GVHD was 25 and 25%, respectively. With a median follow-up period of 39 months (range: 5-112 months) the overall survival was 100%, while thalassemia-free survival was 80%. Although the results of our study look promising, larger cohorts of patients and prospective clinical trials are required to confirm the benefits of our approach as a possible better alternative to the existing protocols.

Safety and efficacy of donor lymphocyte infusions following mismatched stem cell transplantation.

The use of a mismatched allograft necessitates T cell depletion for prevention of uncontrolled graft-versus-host disease (GVHD), thus impairing a graft-versus-leukemia effect. Data on donor lymphocyte infusion (DLI) after mismatched stem cell transplantation are lacking. Our experience with 28 patients (treated with 59 mismatched DLIs; range, 1-7) is described. The procedure was prophylactic in 6 patients (9 DLIs) and therapeutic in 22 (50 DLIs). DLI dose ranged from 10(2) to 1.5 x 10(9) T cells/kg. In the 6 patients receiving prophylactic DLI, complete remission was maintained in 5; however, 2 died from GVHD. Clinical response to therapeutic DLI was seen in 6 of 22 (27.3%) patients; a greater tumor burden produced a lower response. GVHD appeared in 13 of 28 patients. Surprisingly, a greater HLA mismatch was associated with a lower risk of GVHD, with 3 of 19 DLIs in 3/6 matching and 16 of 29 DLIs in 5/6 matching with similar follow-up. Nevertheless, no correlation between efficacy and HLA mismatching was noted. Death was frequent and usually related to the basic disease rather than to DLI complications. We conclude that mismatched DLI is feasible and may be effective, especially if given soon after transplantation. Future developments using cell therapy with selective or targeted anticancer activity are warranted, with special attention to prophylactic treatment of T cell depleted mismatched allografts recipients.

Fludarabine-based reduced intensity conditioning for stem cell transplantation of Fanconi anemia patients from fully matched related and unrelated donors.

Reduced intensity conditioning has been suggested as a desirable therapeutic modality for the treatment of patients with malignant and nonmalignant indications, but it seems particularly attractive for patients with Fanconi anemia due to their increased sensitivity to chemoradiotherapy. Between November 1996 and September 2003, 7 patients (1 male and 6 female; age range, 3-31 years; median age, 9.5) were conditioned with a fludarabine-based protocol for stem cell transplantation without radiation. In vivo T-cell depletion was accomplished with anti-thymocytic globulin or Campath-1H (alemtuzumab). Graft-versus-host disease prophylaxis consisted of low-dose cyclosporine alone. Eight transplantations were carried out for 7 patients using bone marrow, peripheral blood, and/or cord blood as sources of stem cells. All patients received transplants from HLA-A, -B, -C, and -DR matched donors, 5 from family members and 2 from matched unrelated donors. One patient did not engraft her first matched unrelated donor and underwent a second transplantation from another matched unrelated donor, after which she engrafted well. All 7 patients are alive and well, fully reconstituted with donor cells, and with 100% performance status. In conclusion, fludarabine-based preparative protocols are well tolerated, facilitate rapid engraftment with minimal toxicity, and should be considered an essential component of choice for patients with Fanconi anemia.

Nonmyeloablative stem cell transplantation for the treatment of cancer and life-threatening nonmalignant disorders: past accomplishments and future goals.

Allogeneic bone marrow transplantation (BMT) or blood stem cell transplantation represents an important therapeutic tool for the treatment of otherwise incurable malignant and nonmalignant diseases. Until recently. autologous and allogeneic BMT or mobilized blood stem cell transplantation was used primarily to replace a malignant, genetically abnormal, or deficient immunohematopoietic compartment, and therefore highly toxic myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies have indicated that more effective eradication of host immunohematopoietic system cells could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion following BMT. Thus eradication of blood cancer cells, especially in patients with chronic myelogenous leukemia and less frequently in patients with other hematologic malignancies, can frequently be achieved despite complete resistance of such tumor cells to the maximum tolerated doses of chemoradiotherapy. Our cumulative experience suggests that graft vs leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host origin. Based on the cumulative clinical experience and experimental data in animal models of human diseases, it appears that induction of host vs graft tolerance as the first step may allow durable engraftment of immunocompetent donor lymphocytes, which may be used for induction of effective biologic warfare against host-type immunohematopoietic cells that need to be replaced, whether they are malignant, genetically abnormal, or self-reactive. Based on this rationale, we speculate that the therapeutic benefit of BMT may be increased by using safer conditioning as part of the transplantation procedure, with the goal of inducing host vs graft tolerance to enable subsequent induction of GVL, possibly graft vs tumor, or even graft vs autoimmunity effects, rather than attempting to eliminate host cells with hazardous myeloablative chemoradiotherapy. Our hypothesis suggests that effective BMT procedures might be accomplished without lethal conditioning of the host, using new, well-tolerated nonmyeloablative regimens, possibly minimizing immediate and late side effects related to myeloablative procedures. Recent clinical data suggest that effective BMT procedures may be accomplished with nonmyeloablative stem cell transplantation (NST) regimens, with no major toxicity. Thus new NST approaches may make BMT procedures safer for a spectrum of clinical indications in children and elderly individuals without lower or upper age limits, while minimizing procedure-related toxicity and mortality. Our cumulative data suggest that high-dose chemotherapy and radiation therapy may be successively replaced by more effective alloreactive donor lymphocytes, thus setting the stage for innovative therapeutic procedures with safer and more effective treatment of patients requiring BMT.

Non-myeloablative stem cell transplantation and donor lymphocyte infusion for the treatment of cancer and life-threatening non-malignant disorders.

Allogeneic bone marrow or blood stem call transplantation (BMT) represents an important therapeutic tool for the treatment of otherwise incurable malignant and non-malignant diseases. Until recently, autologous and allogeneic bone marrow and mobilized blood stem cell transplantations were used primarily to replace malignant, genetically abnormal or deficient immunohematopoietic compartments, and therefore highly toxic myeloablative regimens were considered to be mandatory for the effective eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies have indicated that much more effective eradication of the host immunohematopoietic system cells can be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion following BMT. Thus, eradication of blood cancer cells, especially in patients with chronic myeloid leukemia and, less frequently, in patients with other hematologic malignancies, can frequently be accomplished despite the complete resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience has suggested that graft-vs.-leukemia (GVL) effects might be a useful tool for the eradication of otherwise resistant tumor cells of host origin. Based on the cumulative clinical experience and experimental data in animal models of human diseases, it appears that the induction of host-vs.-graft tolerance as an initial step may allow the durable engraftment of donor immunocompetent lymphocytes, which may be used for the induction of effective biologic warfare against host-type immunohematopoietic cells that need to be replaced, including malignant, genetically abnormal or self-reactive cells. Based on the aforementioned rationale, we speculated that the therapeutic benefit of BMT may be improved by using safer conditioning as part of the transplant procedure, with the goal being to induce host-vs.-graft tolerance to enable subsequent induction of GVL, possibly graft-vs.-tumor or even graft-vs.-autoimmunity effects, rather than attempting to eliminate host cells with hazardous myeloablative chemoradiotherapy. This hypothesis suggested that effective BMT procedures could be accomplished without lethal conditioning of the host, using new well-tolerated non-myeloablative regimens, thus possibly minimizing immediate and late side-effects related to the myeloablative procedures until recently considered to be mandatory for the conditioning of BMT recipients. Recent clinical data presented in this review suggest that effective BMT procedures may be accomplished with well-tolerated non-myeloablative stem cell transplantation (NST) regimens, with no major toxicity. Thus, new NST approaches may offer the feasibility of safer BMT procedures for a large spectrum of clinical indications in children and elderly individuals, without lower or upper age limits, while minimizing procedure-related toxicity and mortality. Taken together, our data suggest that high-dose chemotherapy and radiation therapy may be successfully replaced by a more effective biologic tool, alloreactive donor lymphocytes, thus setting the stage for innovative therapeutic procedures for safer and more effective treatment of patients in need of BMT.

Osteopetrosis: a single centre experience of stem cell tranisplantation and prenatal diagnosis.

Malignant osteopetrosis (MOP) is an autosomal recessive disease in which osteoclast dysfunction results in excessive bone deposition and early infant death. Thirteen children suffering from MOP from four related families all belonging to one Bedouin tribe, were studied. The disease was diagnosed as early as at a few days postnatal to 5 months. Nine children underwent BMT, four of whom are still alive; one is blind and two have markedly reduced vision. Four children who did not undergo BMT died between 4 and 6 months of age. Recently, the gene for MOP has been mapped for this Bedouin tribe allowing prenatal diagnosis. Seven pregnancies were subsequently prenatally diagnosed and two fetuses were found to be affected. Pregnancy was electively terminated in one case. In the other case the parents refused and after establishing the diagnosis, the newborn was transplanted at the age of 7 days.

Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation.

OBJECTIVE: Matched unrelated bone marrow transplantation (BMT) for patients with hematological malignancies is associated with a high incidence of transplant-related complications due to high doses of chemoradiotherapy administered pre-BMT to ensure engraftment. The aim of this study was to investigate the feasibility of low-intensity conditioning for BMT from matched unrelated donors. MATERIALS AND METHODS: Sixteen patients with hematologic malignancies underwent non-T-cell-depleted BMT following a low-intensity conditioning regimen consisting of fludarabine monophosphate 30 mg/m(2)/day for 6 days, busulfan 4 mg/kg/day for 2 days, anti-T lymphocyte globulin 10 mg/kg/day for 4 days. Seven of the patients suffered from chronic myelogenous leukemia, four from acute lymphoblastic leukemia, four from acute myelogenous leukemia, and one from Ki-1 non-Hodgkin's lymphoma. Three of the patients had secondary leukemia and two were post-autologous BMT (ABMT). All patients were transplanted from fully matched unrelated donors. RESULTS: Fifteen of the 16 patients had 100% donor chimerism; no graft rejection was observed. None of the patients developed >Grade II veno-occlusive disease, sepsis, multiorgan failure, or renal or pulmonary toxicity. Four patients died posttransplant; one of thrombocytopenia and severe hemorrhagic cystitis, one of central nervous system toxicity, one of Grade IV graft-vs-host disease, and one following relapse (9 months post-BMT). Survival and disease-free survival at 36 months are 75% (95% confidence interval 46-90%) and 60% (95% confidence interval 30-80%), respectively. CONCLUSION: These results indicate that low-intensity conditioning is sufficient to ensure stable engraftment of bone marrow grafts in a matched unrelated setting.

Immunotherapy of hematologic malignancies and metastatic solid tumors in experimental animals and man.

Following engraftment of donor hematopoietic cells and induction of host-versus-graft tolerance, immunocompetent lymphocytes of donor origin can induce graft-versus-leukemia (GVL) and graft-versus-tumor (GVT) effects. Engraftment of allogeneic bone marrow cells can be accomplished following non-myeloablative conditioning while possibly controlling graft-versus-host disease (GVHD). GVL and GVT effects may thus be successfully accomplished following non-myeloablative stem cell transplantation (NST) as shown by data derived from experimental animals and man.

Engraftment of marrow allografts treated with Campath-1 monoclonal antibodies.

We have analyzed the factors associated with engraftment in 216 recipients of T-cell depleted allogeneic HLA identical sibling marrow transplants using Campath 1 monoclonal antihuman lymphocyte (CD52) antibodies. The patient population consisted of 168 patients with hematologic malignancies, 26 with severe aplastic anemia (SAA), and 22 with hemoglobinopathies, half of whom received marrow treated in vitro with Campath-1M (IgM) and half received marrow with Campath-1G (IgG2b isotype). Patients with durable engraftment had fast hematopoietic recovery: SAA patients reached ANC > 0.5 x 10(6)/L on Day 14; those with leukemia attained ANC > 0.5 x 10(6)/L on Days 18, 17, and 15 for ANLL, ALL and CML respectively, while patients with thalasemia reached ANC > 0.5 x 10(6)/L on Day 21. Overall, 24 patients (17 with leukemia, 4 with SAA, and 3 with thalassemia) suffered graft failure: 10 patients (all grafted with Campath-1M) rejected their grafts, while 14 others (9 grafted with Campath-1M, and 5 with 1G isotype) never engrafted (p = 0.009). Multivariate analysis revealed that neither pretransplant protocol, nor stage of disease or type of antibody used, donor sex and ABO match had any impact on engraftment. The variables favorably associated with engraftment were older age (p = 0.030, RR = 1.016) and CFU-GM number (p = 0.013, RR = 1.001). Patients with ANLL or SAA had a better chance to engraft (p = 0.027, RR = 1.400; and p = 0.003, RR = 2.677, respectively) compared to patients with thalassemia (p = 0.001, RR = 0.551). A higher concentration of Campath-1 antibody in vitro and in vivo adversely affected engraftment. Our data show that satisfactory engraftment can be achieved in patients transplanted with Campath-1 treated marrow allografts. However, despite the measures undertaken to prevent rejection, graft failure still poses a problem. Further pretransplant immunosuppression and perhaps more selective T-cell depletion may reduce the increased graft failure in these patients.

Fludarabine-based protocol for human umbilical cord blood transplantation in children with Fanconi anemia.

PURPOSE: A novel conditioning regimen of fludarabine monophosphate (FLM), anti-T-lymphocyte globulin (ATG), and low-dose cyclophosphamide with no irradiation for human umbilical cord blood transplantation (HUCBT) for the treatment of Fanconi anemia (FA) is described. PATIENT AND METHODS: A 12-year-old girl with FA received a human umbilical cord blood transplant from a fully matched sibling donor. After the HUCBT, the patient was given granulocyte colony stimulating factor in combination with erythropoietin. Pretransplant conditioning consisted of FLM (30 mg/m2/d) from day -10 to day -5, cyclophosphamide (10 mg/kg/d) on day -7 and -6, and rabbit ATG (ATG-Frasenius, 10 mg/kg/d) from day -4 to day -1. Cyclosporin A (3 mg/kg/d) was administered from day -1 as graft-versus-host disease prophylaxis. Cord blood from a sibling donor was used as a source of hematopoietic stem cells. RESULTS: Engraftment was normal and sustained. The regimen was well tolerated with very mild toxicity and no major transplant-related complications or >grade II graft-versus-host disease. Chimerism was 100% donor origin as determined by restriction fragment length polymorphism. CONCLUSIONS: It is possible to achieve sustained engraftment and only mild toxicity in FA after HUCBT with a conditioning regimen of FLM, ATG, and cyclophosphamide with no irradiation. These preliminary results with this novel conditioning protocol are encouraging and should be evaluated in a larger group of patients with FA undergoing HUCBT.

The role of recombinant human erythropoietin in the treatment of thalassemia.

The rationale for treatment with recombinant human erythropoietin (rHuEPO) in thalassemia came from studies in baboons, thalassemic mice and in erythroid cultures. The results demonstrated an increase in gamma globin synthesis and consequently in fetal Hb (Hb F) resulting in improvement in erythropoietic parameters. In addition, endogenous serum Epo levels in various forms of thalassemia were inconsistent and not related to the severity of the anemia. Therefore, several preliminary studies with rHuEPO were performed, mainly on patients with beta thalassemia intermedia. The results indicate: a) a significant, dose-related (500 u/kg to 1000 u/kg x 3/week) increase in thalassemia erythropoiesis without changes in % of Hb F, MCV and MCH, mainly in splenectomized patients; b) the minimum effective dose is 500 u/kg x 3/week; c) there were no major side effects during the continuous treatment period of 9 months. In order to improve both quantitative and qualitative thalassemia erythropoiesis, several trials were undertaken combining rHuEPO with hydroxyurea (HU), which is known to increase % Hb F, MCV and MCH without a major effect on Hb levels. The designed trial included 3 to 6 months of HU alone (20 mg/kg x 4/week), or with rHuEPO alone (500 u/kg x 3/week or 375 u/kg x 2/week) or a combination of the two drugs. The results show an additive effect of the two drugs, in some of the patients. It is not known whether the addition of oral iron to rHuEPO is warranted for maximal erythropoietic response. The major limiting factor in designing large scale clinical trials is the relatively high cost of the drug. Nevertheless rHuEPO alone or in combination with other Hb F modulating drugs may have a positive effect in thalassemia with resulting improvement in the quality of life.

Enhanced lymphoid cell recovery after bone marrow transplantation: correlation with the presence of costimulatory antibodies in serum.

We describe a patient with T cell deficiency who underwent bone marrow transplantation (BMT) from an HLA-identical brother. The patient's white blood cell count recovered with exceptional rapidity post-BMT: after 7 to 9 days it rose sharply to 98x10(9) cells/L, 76% of which were mononuclear leukocytes. It then decreased, and a second peak was observed 250 days post-BMT. Lymphocytes from both peaks displayed a phenotype of mature T cells together with characteristics of a constitutively activated state; that is, they 1) exhibited high levels of tyrosine-phosphorylated T cell receptor (TCR) zeta chain, 2) spontaneously secreted IL-2, 3) expressed activation specific cell surface markers, and 4) were unresponsive to in vitro stimuli. The increased cell counts in both peaks correlated with the presence of anti-lymphocytic antibodies in the patient's serum, which reacted with peripheral blood lymphocytes (PBLs) both from the donor and from unrelated individuals. These antibodies were present before BMT and reappeared post-BMT. Variable number tandem repeats analysis revealed that the patient's PBLs were chimeras for up to 2 years post-BMT. This finding could explain the newly synthesized post-BMT anti-lymphocytic antibodies and the appearance of the second WBC peak during that period. The patient's anti-lymphocytic antibodies displayed costimulatory activity, enhancing the in vitro proliferation of normal T cells suboptimally activated via the TCR. The unique characteristics of these antibodies could explain the enhanced T cell recovery observed post-BMT as well as the constitutive activation state of these cells. Furthermore, such antibodies may eventually facilitate development of a therapeutic method for inducing enhanced post-BMT recovery.