Brief report: correction of X-linked hyper-IgM syndrome by allogeneic bone marrow transplantation.
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Publications and source records attributed to E Haddad.
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We have retrospectively analyzed the outcome of bone marrow transplantation (BMT) in 14 patients with leukocyte adhesion deficiency (LAD) performed in two centers between 1981 and 1993. Five patients received BMT from HLA-identical donors. Nine received T-depleted marrow from two HLA antigen- or haplotype-incompatible parents. Conditioning regimen consisted of chemotherapy exclusively in 13 patients and associated with total body irradiation (TBI) in one patient. In five cases, failure of engraftment occurred as a result of either insufficient myeloablation (n = 3) or, possibly, graft rejection in two cases of moderate phenotype of LAD. The second conditioning regimen consisted of TBI and chemotherapy with the use of anti-lymphocyte function-associated antigen 1 (LFA-1) and anti-CD2 monoclonal antibodies for patients with the moderate phenotype of LAD. These patients were successfully retransplanted. Eight patients developed acute graft-versus-host disease (GVHD). Chronic GVHD occurred in five cases. GVHD led to the death of three patients. Ten patients are alive and well 12 months to 12 years after BMT. Chimerism is full in six of these patients and mixed but stable in four with variable proportion of donor leukocytes. One patient with less than 15% donor leukocytes has mild gingivitis, while the others are well. Sequelae from BMT are limited in two cases to growth retardation caused by TBI. Success of BMT in cases of LAD including seven of nine recipients of HLA nonidentical marrow indicates that this procedure can be proposed as a curative approach to LAD regardless of an available HLA-identical donor. Great care should be taken in GVHD prophylaxis and treatment.
The aim of the present study was to compare the preventive effect of a nondepleting monoclonal antibody specific for the LFA-1 alpha chain (CD11a) on the rejection of bone marrow, vascularized cardiac, and nonvascularized skin grafts in the same haplotype-disparate mouse strain combination. A 7-day treatment with a total dose of 0.5 mg of anti-LFA-1 antibody (H-129) had no effect on the rejection of BDF1(H-2b/d) skin grafts by CDF1 (H-2k/d)-treated mice. In contrast, the same treatment regimen significantly prolonged the survival of BDF1 cardiac allografts in CDF1 mice: 7 out of 10 mice had a functional graft after 70 days, whereas all control mice had rejected their graft by 11 days. Nevertheless, cardiac allografts were ultimately rejected. In contrast, infusion of anti-LFA-1 antibody was able to promote definitive engraftment of T-depleted BDF1 marrow in 9 gray-irradiated CDF1 recipients: in surviving mice, engraftment increased from 10% in controls to 78% in antibody-treated recipients. In mice that tolerated their cardiac graft for more than 70 days, there was a slight delay in the rejection of donor skin graft but no in vitro evidence of tolerance. In contrast, mice with successful marrow engraftment did not reject donor skin graft and failed to mount proliferative and cytotoxic responses against donor alloantigens, whatever the percentage of engrafted donor leukocytes. These results indicate that a nondepleting anti-LFA-1 antibody can efficiently protect against rejection of MHC-incompatible heart and bone marrow. The protective effect of anti-LFA-1 antibody was associated with the induction of T cell tolerance toward donor antigens after bone marrow transplantation.
Chediak-Higashi syndrome is a rare condition characterized by susceptibility to bacterial infections, defective natural killer activity, and episodes of macrophage activation known as accelerated phases. Chemotherapy can induce transient remission of the accelerated phase, but relapses become less and less sensitive to treatment and ultimately lead to death. Allogenic bone marrow transplantation (BMT) has been proposed as a curative treatment for Chediak-Higashi syndrome. We report the outcome of BMT in 10 such children. Seven received marrow from an HLA-identical related donor and three from an HLA-nonidentical related donor. Three patients died, two from a new accelerated phase after rejection of transplanted bone marrow and one from cytomegalovirus (CMV) pneumonia. Six of seven recipients of HLA-identical marrow and one of three recipients of HLA-nonidentical marrow are alive and well without treatment 1.5 to 13 years after transplantation (median, 6.5 years). No manifestations of accelerated phases have occurred in these seven patients, and significant natural killer activity is detectable. Interestingly, BMT prevented recurrence of accelerated phases in patients with limited numbers of donor-type leukocytes after transplantation. Ocular and cutaneous albinism were not corrected after transplantation. None of the patients developed serious toxic reactions to the BMT conditioning regimen or have long-term sequelae. These results show that HLA-identical BMT is an acceptable curative treatment for Chediak-Higashi syndrome, whereas HLA-nonidentical BMT remains an experimental approach.
No studies have accurately reported on the total dietary fiber content of current military dining facility meals. The military nutrition data base is incomplete for total, insoluble, and soluble dietary fiber content. The Military Recommended Dietary Allowances has no recommendation for dietary fiber. The American Dietetic Association advises all Americans to consume 25 to 35 g/day. This study estimated total dietary fiber intake from a calculated analysis of a 6-day weighed military ration. The calculated fiber values for the sample military diet provided 6.8 g of total dietary fiber per 1,000 kcal. Substituting whole-grain cereal products for all the refined cereal products increased the fiber to 9.5 g/1,000 kcal. Calculated results were validated by chemical analysis. Total dietary fiber was 4.1 g/1,000 kcal for the sample military diet and 5.6 g/1,000 kcal for the whole-grain test diet. Fiber content of the sample military diet was well below recommended levels but similar to that found in other studies on the typical American diet.
PURPOSE: This study is presented to help define the role of radiotherapy in the management of epidemic Kaposi's sarcoma. METHODS AND MATERIALS: Between June 1986 and June 1993, we treated 453 patients who had acquired immunodeficiency syndrome related Kaposi's sarcoma. Two hundred fifty-two patients (55.6%) had received previous treatment for their Kaposi's sarcoma: 228 (55.3%) with interferon, and 116 (25.6%) with Vinblastine. Depending on both tumour size and location, patients were treated with extended cutaneous irradiation using 4 MeV electron beam energy and/or localized irradiation using 45-100 kV x-ray (cutaneous lesions), or 4 MV x-ray (oral tumours). A total of 5015 courses of radiation therapy was given. The intention of the treatment was closely linked to the anatomic sites. Multiple courses of treatment ranging from 10 to 20 Gy (2.5 Gy/fraction, 4 times/week) were used for Kaposi's sarcoma involving conjunctiva (n = 32 treatments), eyelids (n = 306), lips (n = 170), hands (n = 208), feet (n = 417), penis (n = 131), oral mucosa (n = 43), and anal region (n = 5). A second group including other cutaneous sites (face, trunk, limbs) was treated with a dose of 30 Gy (20 Gy in 2 weeks followed by 2 weeks rest and then a second series of 10 Gy in 1 week). RESULTS: For the first group, tolerance was generally good excluding oral cavity irradiation, with an effective palliation of symptoms (87.8% overall rate of objective responses); an enhanced mucosal reactions was noted in patients receiving oropharyngeal irradiation. For the second group, a complete regression rate of 85% was observed; tolerance was acceptable: complications were severe epidermitis with skin ulceration (5%), exsudative epidermitis (26%), dry epidermitis (60%), and varying degrees of erythema (9%). There was a significant correlation between risk of recurrence (overall recurrence rate of 71% after an average of 7.5 months) and occurrence of opportunistic infections: 85% of recurrences appeared concomitantly with accelerated course of acquired immunodeficiency syndrome. CONCLUSIONS: We conclude that radiotherapy is an efficient treatment for epidemic Kaposi's sarcoma (EKS): doses of 15.2 Gy for oral lesions and 20 Gy for lesions involving conjunctiva, eyelids, lips, hands, feet, penis, and anal region were sufficient to produce shrinkage of the tumour and good palliation of symptoms. For the other cutaneous sites, 30 Gy local field irradiation could be safely given with better short-term response. Prophylactic measures with antifungal treatment should be systematically associated with oropharyngeal irradiation, to improve tolerance to the treatment.
From January 1987 to December 1992, 420 patients with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi's sarcoma (EKS) were treated with radiotherapy at the oncology department in the Henri Mondor Hospital. Of these, 146 (34.7%) exhibited tumours at 186 sites; 35 were oral, 102 eyelid or conjunctival (ophthalmic), and 49 penile or scrotal (genital) sites. Most patients had received prior chemotherapy. Radiation therapy consisted of 4 MV or 45 kV X-rays, depending on tumor size and location. Doses ranged from 10 to 30 Gy, according to tumor response and toxicity. In oral lesions mucosal reactions were often observed after relatively low doses of radiotherapy. In 27 patients receiving 15 Gy, severe reactions were observed in 6 (22%), moderate reactions in 4 (15%) and mild reactions in 17 (63%). By contrast, irradiation of eyelid or conjunctival lesions and genital lesions, was well-tolerated. Treatment was generally successful in achieving good symptom palliation. Eyelid and conjunctival Kaposi's sarcoma seemed to be more radiosensitive when compared with cutaneous sites: a high objective remission rate (96%, 98/102) was observed at doses ranging from 10 to 20 Gy. Penile and scrotal lesions showed a good response to low dose radiation (complete response was scored in 34/49 patients (69.4%)). A meticulous evaluation of tolerance was necessary. Toxicity of oropharyngeal irradiation at relatively low doses is an argument for a restrictive use of this procedure in oral lesions.
PURPOSE: We have reviewed the results of 165 T1 and T2 squamous cell carcinomas of the faucial arch treated by definitive irradiation including or not Iridium 192 brachytherapy to ascertain whether a significant relationship existed between Iridium implantation, local control, complications, and survival. METHODS AND MATERIALS: From March 1971 to November 1990, 58 T1 and 107 T2 (NO: 107/165; N1: 30/165; N2: 9/165; N3: 19/165) biopsy proven squamous cell carcinomas of the tonsillar region (104/165) and the soft palate and uvula (61/165) were treated in Henri Mondor Hospital by definitive irradiation with curative intent. From 1971 to 1981 (period 1), only guide gutter technique was available, so that implants were reserved for small tumors: patients were either managed by definitive telecobaltherapy to tumor site and neck node areas (Group 1; n = 48; mean dose: 70 Gy; confidence interval: +/- 5.5; 5 fractions of 1.8 Gy per week) or by exclusive Iridium implant (Group 2; n = 11; all T1NO; 64 Gy +/- 4.8) or by a combination of external beam radiation therapy to tumor site and neck nodes areas and Iridium implant (Group 3; n = 40). In 1981 (Period 2), a new plastic tube technique, which enables implantation of larger areas, was introduced in the department and all patients (Group 4; n = 66) were then managed by external radiation therapy (Group 3 + 4: 47 Gy +/- 4.3) followed by an Iridium implant (31 Gy +/- 10.5). Clinically positive neck nodes either received additional external dose with electrons or were excised. RESULTS: Overall 5-year survival (Kaplan Meier) was 21%, 50.5%, and 60% in groups 1, 2, and 3 + 4, respectively (p < 0.001, log rank). Five-year local control was 58%, 100%, and 91%, respectively (p < 0.001). Five-year necrosis rate was 4.5%, 20.5% and 18%, respectively (N.S.). Comparison of results between the two periods of the study (Group 1 + 2 + 3 vs. group 4) show that these two groups are statistically comparable according to site and size of tumor and N status and that both local control (77% vs. 94% at 5 years; p < 0.01) and disease-free survival (56% vs. 71%; p = 0.03) were improved after 1980, while there was a trend to an increase in overall survival (42% vs. 53% at 5 years; p = 0.08); nodal control (86% vs. 95% at 5 years), and necrosis rate (11% vs. 20% at 5 years) were not modified. Multivariate analysis showed that both local control (p < 0.0001) and overall survival (p < 0.0001) were improved when tumor was implanted. CONCLUSION: We recommend then to treat T1 and T2 squamous cell carcinomas of the faucial arch by external radiation therapy to tumor site and neck areas (45 Gy/25 fractions/5 weeks) followed by a 30 Gy Iridium implant and, for patients with clinically positive nodes, either a further 25-30 Gy electron beam irradiation to the nodes or neck node dissection.
Primary or secondary nocturnal enuresis in adults (over the age of 15 years) is rare, but is associated with considerable psychosocial repercussions. The aim of this retrospective study was to determine whether urodynamic studies have any predictive value for the efficacy of the treatments proposed in these patients. This study was based on 20 patients (8 females and 12 males) between the ages of 15 and 33 years (mean: 23.75 years), studied between 1982 and 1990 with a mean follow-up of 13.35 months. Enuresis was primary in 12 patients and secondary in 8 patients. 11 patients had already received one or more treatments without success. Patients with clinically obvious neurological disease were excluded from the study. The urodynamic assessment included water cystomanometry, water urethromanometry with a perfused catheter and uroflowmetry. In addition to the investigation of other associated disturbances of micturition, the following complementary investigations were performed: urine culture in every case, IVU and/or cystography (n = 18), cystoscopy (n = 3), renal and vesical ultrasonography (n = 1). The urodynamic assessment was abnormal in 16 out of 20 cases: marked detrusor hyperactivity (n = 15), impaired compliance (n = 6), significant urethral instability (n = 7), isolated premature urge (n = 1). 15 patients presented with diurnal disorders dominated by frequency (n = 13), urgency (n = 9) and urge incontinence (n = 4); detrusor hyperactivity was detected in every case. The abnormalities observed on the urodynamic assessment guided treatment, allowing correction of enuresis in 3/4 of cases.(ABSTRACT TRUNCATED AT 250 WORDS)
The risk of second cancer in the head and neck region following definitive radiation therapy was evaluated among 600 patients who were treated for T1 and T2 cancers of the oral cavity and oropharynx at the Henri Mondor hospital between January 1970 and March 1987. Seventy-five patients (12.5%) were managed with external irradiation only, 243 (40.5%) with RT and Iridium 192, and 282 (47%) with Iridium 192 alone. One hundred fifteen patients (19%) developed a second cancer from 3 to 183 months after initial therapy (median: 32 months), including 69 patients (11.5%) in whom the second malignancy was diagnosed in the head and neck region. An increased and constant actuarial risk of development of second head and neck cancer was found (2.7%/year of observation). Univariate analysis showed that age, sex, stage, and modality of the initial treatment did not influence the risk of second head and neck cancer; there was a greater risk of second head and neck malignancy for those patients with soft palate carcinoma (p less than 0.05). Multivariate analysis revealed that the only group of patients who developed a second head and neck cancer more frequently were those who were irradiated with Iridium 192 only (p = 0.0076). There was a trend toward a greater risk of second head and neck malignancy for those with soft palate carcinoma (p = 0.059). Radical treatment of the second head and neck malignancy by surgery and/or re-irradiation was performed for 67% of patients. Patients initially treated by Iridium 192 only could undergo salvage treatment more often than those who previously received external beam radiotherapy (79% vs 53%, p = 0.02). The overall 2-year and 5-year survivals after the diagnosis of the second head and neck cancer were 32% and 10%, respectively.
Ecologic and philosophic as well as health concerns have led to an increasing number of adolescent vegetarians. The various types of vegetarianism differ substantially in dietary composition. Benefits of the vegetarian diet must be balanced by careful attention to ensuring adequate intake of protein and amino acids as well as certain vitamins and minerals that tend to be less available in plant foods.
This is a retrospective analysis of 233 evaluable patients with stage I-II squamous cell carcinoma of the oral cavity treated by definitive branchytherapy. Minimum follow-up is 3 years. Treatment of neck was chosen by a multidisciplinary team, according to age, medical status and availability for regular follow-up. One hundred and ten patients (47%) underwent elective neck dissection (END); 28 (25%) had positive nodes and received neck irradiation post-operatively. One hundred and twenty three patients (53%) were regularly followed up only, with therapeutic neck dissection (TND) reserved for cases of node relapses. In the END group, there were 19 neck relapses (17%): 12/60 (20%) in patients with mobile tongue carcinoma and 7/50 (14%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 9/19 (47%) cases. In the TND group, there were 21 neck relapses (17%): 16/82 (20%) in patients with mobile tongue carcinoma and 5/41 (10%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 13/21 (62%) cases. Ten-year survival is 37% for the END group and 31% for the TND group. Tumour stage and infiltration into underlying tissues increased the probability of neck relapse and death. Furthermore, a multivariate analysis showed that patients treated in the TND group had a higher probability of death than patients treated in the END group (p less than 0.04).
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One hundred and ten patients with Stage II epidermoid carcinomas of the mobile tongue were treated by interstitial irradiation (Group I: 85 patients) or external irradiation to the primary and the regional lymphatics followed by an interstitial boost (Group II: 25 patients). The neck was managed by either an elective neck dissection (43 patients) completed by external irradiation in 13 patients with pathological specimen or close follow-up (40 patients) with therapeutic neck dissection for relapses (7 patients) in Group I. Primary local control was 88% in Group I and 36% in Group II. Regional control was 91% in Group I and 5/6 in Group II for patients whose primary tumor was controlled. Five-year absolute disease-free survival (DFS) was 42% in Group I and 24% in Group II, but there was an imbalance in the distribution of larger tumors favoring Group I. There were 30 radiation-induced complications and four patients required corrective surgery. This retrospective analysis showed better results in patients whose primary was treated by interstitial irradiation alone which has the extra advantage of preserving salivary function.
From 1970 to 1986, 117 patients with T1 (47) or T2 (70) epidermoid carcinomas of the floor of the mouth (SCC) were treated by iridium-192 implantation (192 Ir). The dose was prescribed according to the Paris System and varied over those years. Follow-up information was available on 116 patients. There were 46 T1N0, 47 T2N0, and 23 T2N1-3. Neck management varied for the 93 N0 patients consisting of surveillance (24 T1, 17 T2) or elective neck dissection (22 T1:all pN-, 30 T2: 20 pN-, 10 pN+). Cause specific survival rates were 94% for T1N0, 61.5% for T2N0, and 28% for T2N1-3 at 5 years. Primary local control was 93.5%, 74.5%, and 65%, respectively, and 98%, 79%, and 65% after salvage. Patients with gingival extension or a tumor size over 3 cm (T2b) had a local control of 50% (9/18) and 58% (15/26), respectively. Nodal control was 93.5% for Stage I, 85% for Stage II, and 48% for T2N1-3 patients. There was no difference in nodal control with regard to treatment policy for Stage I-II patients. There were few complications including three deaths: two from surgery and one from 192 Ir. Nodal status, tumor size defined as T1, T2a (less than or equal to 3 cm), T2b (greater than 3 cm), and gingival extension were the only independent prognostic factors. The management of T1N0 and T2N0 SCC by 192 Ir to a dose of 65 or 70 Gy, using the Paris System, is recommended for lesions 3 cm or less and without gingival extension.
Between 1970 and 1986, 166 patients with T1 or T2 epidermoid carcinomas of the mobile tongue were treated by iridium 192 implantation (70 T1N0, 83 T2N0, 13 T1-2 N1-3). Five-year actuarial survival was 52% for T1N0, 44% for T2aN0, and 8% for or T1-2 N1-3. Cause specific survivals were 90%, 71%, and 46%, respectively. Local control was 87% for both T1N0 and T2N0, and 69% for T1-2 N1-3. Seven of 23 failures were salvaged by surgery, increasing local control to 96% for T1 and 90% for T2. Thirty-six patients developed a minor or moderate necrosis (16% T1, 28% T2). Half of these involved bone but only five required surgical intervention. Both local control (LC) and necrosis (nec) increased with increasing dose but improvement beyond 65 Gy is minimal (less than or equal to 60 Gy: LC = 78% nec = 13%; 65 Gy: LC = 90% nec = 29%; greater than or equal to 70 Gy: LC = 94% nec = 23%). For N0 patients, neck management consisted of surveillance (n = 78), elective neck dissection followed with external irradiation for pathologically positive nodes (n = 72), or irradiation (n = 3). Clinically positive nodes (13 patients) were managed by either neck dissection followed by external irradiation if pathologically positive (n = 10) or irradiation alone (n = 3). Regional control was 79% for N0 patients, improving to 88% after surgical salvage, and was 9/13 for N1-3 patients. We recommend that T1 and T2 carcinomas of the mobile tongue be treated by iridium 192 implantation to deliver 65 Gy. Mandibular necrosis should be reduced by using an intra-oral lead-lined dental mold.
Between June 1986 and December 1988, 149 patients with AIDS-related Kaposi's sarcoma were treated by cutaneous irradiation in our department. According to Mitsuyasu's staging, 34 patients (23 p. 100) were stage I, 82 (55 p. 100) stage II and 33 (22 p. 100) stage IV; no stage III was reported. Fifty eight patients (39 p. 100) had previously presented with one or several opportunistic infections. Ninety four patients (63 p. 100) had previously received treatment with interferon in 85 (57 p. 100) and/or Velbe in 43 (29 p. 100). 319 cutaneous localisations were treated, 59 p. 100 by extended cutaneous irradiation, using 4 and/or 8 MeV electron beam energy, and 41 p. 100 by localized irradiation, using 45 kVX-ray energy, 2.5 Gy/fraction, 4 times a week by split course 20 Gy then 10 Gy two weeks later. Twenty patients (13 p. 100) with oedema of the lower limbs were treated, using 4 MV photon therapy with bolus, and 3 (2 p. 100) were treated for lesions in the ENT regions. Only 131 patients were evaluable (257 localisations); 62 p. 100 obtained complete remission and 31 p. 100 partial remission after a mean period of 1.5 months (0.5-3 months). The overall tolerance was acceptable. The complications were epidermitis with some necrosis (8 p. 100), exudative epidermitis (26 p. 100), moderate epidermitis (63 p. 100) and slight reactions in 4 p. 100. The mean recurrence time was 5 1/2 months.
Electron beam irradiation of the entire skin surface was used to treat 25 patients with mycosis fungoides from 1977 to January 1988. A plexiglas screen was used to reduce the energy of the 8 MeV beam of a Sagittaire linear accelerator to 4 MeV. A total dose of 30 Gy was delivered in 12 fractions over days. This series includes 17 men and 8 women with a mean age of 44 years (range 13-78 years) and a mean follow-up of 34 months (range 6-92 months). The following-up staging system was used: stage A: superficial lesions covering less than 50 p. 100 of the body surface; stage B: superficial lesions covering more than 50 p. 100 of the body surface; stage C: tumors of the skin, lymph nodes and/or visceral organs, Sezary's syndrome. All stage A patients achieved complete remission. One developed recurrent disease in a very limited area 17 months after radiation therapy. No stage A patient died of mycosis fungoides. 6/9 stage B patients achieved complete remission; 4 of these developed recurrent disease localized to the skin 6 to 13 months after electron therapy. These recurrences were controlled by topical nitrogen mustard, puva therapy or localized irradiation. 1 patient showed no response and died of cutaneous mycosis fungoides. 5/10 stage C patients obtained complete remission but all relapsed within a mean period of 7 months. 4/5 of the patients not responding to electron therapy died of their disease and one is alive 16 months after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)