Unilateral renal agenesis with pelvic renal ectopy.
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Humans↗
Biomedical subjects
S Singhal
Publications and source records attributed to S Singhal.
Comparison of new patients with Bence-Jones, IgG and IgA myeloma receiving sequential therapy: the need to regard these immunologic subtypes as separate disease entities with specific prognostic criteria.
Of the 61 newly diagnosed patients with Bence-Jones (BJ) myeloma presenting to our centre between May 1986 and December 1997, 53 received sequential therapy (ST) comprising infusional chemotherapy (IC) followed by high-dose therapy and autotransplantation with interferon-alpha2b maintenance. The outcome was compared with 153 IgG and 39 IgA similarly treated myeloma patients. Response to IC and high-dose was comparable between the three subtypes but a significantly higher proportion of patients with BJ myeloma failed to receive high-dose compared to IgG (P = 0.003) and IgA (P = 0.04) myeloma. Median overall survival (OS) of patients with BJ myeloma (2.8 years) and event-free survival (EFS, 1.2 years) was significantly shorter than for patients with IgG myeloma (4.5 years, P = 0.03 and 2.1 years, P = 0.03, respectively). However, among those patients who achieved complete remission there was no difference in OS and EFS between IgG and BJ myeloma. In distinction to IgG myeloma where age and beta2M were significant, Cox analysis on presentation features identified performance status and urine total protein as having significant impact on OS. We conclude that achieving CR is an important treatment aim in patients with BJ myeloma, conferring a similar outlook on survival as in patients with the IgG subtype, and there is a need to consider different subtype-specific staging systems when evaluating the results of published or ongoing therapeutic trials.
Adult↗
CD34(+) cell collection efficiency does not correlate with the pre-leukapheresis hematocrit.
One hundred and seventy-seven large-volume leukapheresis procedures performed on 91 patients over a 15 month period were reviewed to see if the pre-apheresis hematocrit (Hct) affected the CD34(+) cell collection efficiency (CE) of the Fenwal CS 3000 Plus cell separator. The Hct was 0.174-0.461 (median 0.317), and the peripheral blood CD34(+) cell count 2-2487 per microl (median 21). The total CD34(+) cell quantity collected was 3.0-2677.2 x 10(6) (median 113.0). Based on the number of CD34(+)cells contained in the blood volume processed (23.3-37303.2 x 10(6); median 318.0), the CE was 1.7-87.5% (median 30.3). No correlation was found between the Hct and CE (r(2) = 0.0034; P = 0.44) or the total CD34(+) cell quantity collected (r2 = 0.0040; P = 0.40). CEs for Hct <0.25 (median CE 36%), Hct 0.25-0.299 (median CE 30%) and Hct 0.30 (median CE 30%) were comparable. As expected, highly significant correlations were seen between the CD34(+) cell quantities collected and quantities processed (r2 = 0.59; P < 10(-6)) as well as the peripheral blood CD34(+) cell counts (r2= 0.60; P < 10(-6)). We conclude that the minimum acceptable Hct or hemoglobin level for leukapheresis should be dictated by clinical circumstances because it does not affect stem cell collection.
Antigens, CD34↗
Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome.
Candidemia is a serious complication in patients following allogeneic blood, marrow, and organ transplantation. Fourteen patients developed nosocomial fungemia among 204 allogeneic marrow transplants performed during 1997-1999. Incidence of hematogenous candidiasis was 6.8 per 100 allogeneic BMT. All 14 had an indwelling central venous catheter (CVC) and fluconazole (100-200 mg daily) was given prophylactically. In 11 (78.5%) neutropenic patients, duration between agranulocytosis and diagnosis of fungemia was (median, +/- s.d.) 10 +/- 8 days. Candida glabrata (53.3%) was the most common yeast species, followed by C. krusei (33.3%), and C. parapsilosis (13.3%). Candida albicans was conspicuously absent. Ten patients (71.4%) had primary transplant-related complication (>2 days) including hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) (n = 5), severe hemorrhagic cystitis (n = 3), and bacteremia (n = 2). Seven (50.0%) patients expired and in three (21.4%) deaths were attributed to fungemia. The impact of a primary transplant-related complication on short-term survival in this setting was not significant (P = 0.07) (HUS/TTP (P > 0.5); neutropenia (P > 0.5); GVHD (P = 0.35)). Removal of CVC did not alter outcome in our group (P > or = 0.5) although in patients with persistent fungemia (>72 h), and those with preceding bacteremia, mortality was significantly higher (P = 0.002). Conventional prognosticators of poor outcome did not adversely effect short-term survival in our transplant recipients with hematogenous candidiasis. The predominance of C. glabrata and C. krusei breakthrough infections was similar to what is seen with high-dose fluconazole (400 mg) prophylaxis, and no adverse effects of low-dose fluconazole in terms of increased incidence of non-susceptible Candida species was seen.
Adolescent↗
Partially mismatched related donor bone marrow transplantation as salvage for patients with AML who failed autologous stem cell transplant.
Treatment options for patients who relapse are limited and the outcome is dismal. Between August 1993 and January 1999, 17 patients, median age 26 (4-44) years, underwent T cell depleted bone marrow transplant from partially mismatched related donors (PMRD), as a salvage for AML relapsing after an autograft. The median time from auto-transplant to relapse was 7 months (1.5-24) and the interval between transplants was 10 months (3-30). All patients had active leukemia at time of transplant. Donors were siblings (n = 8), parents (n = 2), daughters (n = 4) and others (n = 3), and 82% were > or = 2 major HLA antigen mismatched with the recipient. The conditioning therapy included total body irradiation in 14 patients and was busulfan-based in three. Graft-versus-host disease (GVHD) prophylaxis consisted of partial T cell depletion along with post-transplant immunosuppression. Median day to engraftment was 16 days (12-20). Acute GVHD was seen in six patients, and chronic GVHD in four of 13 surviving beyond 100 days. Ten patients died of non-relapse causes, at 1-588 (median 77) days. Two patients relapsed at 3 and 4 months. Five patients (29%) are surviving leukemia-free 42-84 months post transplant (median 68 months). A short interval between transplants was predictive of early relapse but not mortality. Age <18 and <2 organ toxicities were marginally predictive of better survival. We conclude that BMT from PMRD is a reasonable option for patients with refractory AML post autograft.
Acute Disease↗
Cervical tuberculous lymphadenopathy: changing clinical pattern and concepts in management.
Tuberculosis is one of the biggest health challenges the world is facing. In this study the clinical pattern of patients with cervical lymphadenitis, who presented to the ear, nose, and throat outpatient department of the Government Medical College Hospital, Chandigarh, India between June 1997 and May 1998 is recorded. Tuberculosis accounted for 60 out of 94 cases of cervical lymph node enlargement. The commonest age group affected was 11-20 years. Constitutional symptoms were not present in most of the patients. Multiple matted nodes were seen in 23 patients but a single discrete node was seen in 18 patients. Upper deep jugular nodes were the most commonly affected lymph nodes. Discharging sinus and abscess formation were uncommon. Fine needle aspiration cytology yielded a positive diagnosis in 52 out of 56 patients. Chest lesions on radiography were evident in 16% of the patients. Mantoux test was positive and was more than 15 mm in most of the patients. This study shows that the classical picture of "scrofula" is no longer seen nowadays and can probably be explained by the earlier presentation of the disease. All the patients were treated with short course daily chemotherapy for six months. Surgery was not required in the majority of patients except in four cases where excision biopsy was performed. Patients with abscess formation were managed with wide bore needle aspiration only. With a minimum six month period of follow up, no patient was found to have a recurrence of local or systemic disease. This study emphasises the role of fine needle aspiration cytology in diagnosis and confirms the efficacy of six months short course chemotherapy.
Adolescent↗
The implication of compromised renal function at presentation in myeloma: similar outcome in patients who receive high-dose therapy: a single-center study of 251 previously untreated patients.
The purpose of the study was to determine the role of sequential therapy (ST) in new patients with myeloma presenting with renal dysfunction (RD): serum creatinine >140 micromol/L (1.6 mg/dL). Between April 1985 and June 1998, 251 patients, 59 (23%) with RD were entered into a ST program comprised of infusional chemotherapy (IC) with VAMP/C-VAMP (vincristine, doxorubicin, and methylprednisolone with/without cyclophosphamide) followed by autologous transplantation and interferon maintenance. The median overall survival (OS) of 251 patients from the start of IC was 4.2 yr with the RD group faring significantly poorer (median 2.5 yr) than those with no renal dysfunction (NRD; median 4.6 yr; p = 0.0025). Mortality during the first 100 d of IC was significantly higher in patients with RD (11/59; p = 0.01) compared to patients with NRD. In patients consolidated with high-dose therapy, the OS and event-free survival (EFS) were not significantly different between the two groups. Cox analysis of the variables at presentation failed to show RD as a factor influencing outcome, but it showed that patients with beta-2-microglobulin (beta2M) > or = 3.7 (p < 0.0001), age > or = 52.5 yr (p = 0.002), performance status (PS) > or = 2 (p = 0.005) and patients with light-chain myeloma (p = 0.03) had a significantly shorter OS, beta2M > or = 3.7, PS > or = 2, and light-chain myeloma were predictive of shorter EFS. The study shows that with modern intensive schedules of treatment, renal disease at presentation in isolation does not compromise outcome.
Adult↗
Thalidomide in cancer: potential uses and limitations.
In addition to immunomodulatory and cytokine-modulatory properties, thalidomide has antiangiogenic activity. It has been investigated in a number of cancers including multiple myeloma, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Its role has been best explored in myeloma, where, at daily doses of 100 to 800 mg, it is remarkably active, causing clinically meaningful responses in one-third of extensively pretreated patients and in over half of patients treated early in the course of the disease. It also acts synergistically with corticosteroids and chemotherapy in myeloma. Thalidomide produces improvement of cytopenias characteristic of myelodysplastic syndrome, resulting in the reduction or elimination of transfusion dependence in some patients. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high grade glioma and, in combination with irinotecan, in some patients with colon cancer. Thalidomide is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation and fatigue are common adverse effects seen in 75% of patients. Symptoms of peripheral neuropathy and skin rash are seen in 30%. A minority of patients experience bradycardia and thrombotic phenomena. Despite the high frequency of adverse effects, those severe enough to necessitate cessation of therapy are seen in only 10 to 15% of patients. A therapeutic trial of thalidomide should be considered in all patients with myeloma who are unresponsive to or relapse after standard therapy. In other malignant diseases, the most appropriate way to use the drug is in the setting of well designed clinical trials. In the absence of access to such studies, thalidomide could be considered singly or in combination with standard therapy in patients with no meaningful therapeutic options.
Animals↗
Primary hyperparathyroidism: what every orthopedic surgeon should know.
The diagnosis of hyperparathyroidism should rarely by missed by the orthopedic surgeon. When a patient presents with a pathologic fracture, routine serum calcium should be obtained. If there is evidence of elevated serum calcium or any of the pathognomonic findings of primary hyperparathyroidism on plain radiographs, total and ionized calcium and an intact parathyroid hormone levels should be obtained to make the diagnosis (Figure 5). When patients require surgical treatment for an orthopedic condition and also need surgery for hyperparathyroidism, the procedures can be safely performed simultaneously. Simultaneous parathyroidectomy corrects the underlying endocrinopathy, thereby improving the outcome of the orthopedic procedure. In addition, these procedures can easily be performed simultaneously under one anesthetic and thereby minimize cost and length of hospitalization.
Aged↗
Antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree-bark powder: a randomised placebo-controlled trial.
OBJECTIVE: To evaluate the antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree bark (a popular cardiotonic substance in Indian pharmacopoeia) and to compare it with a known antioxidant, vitamin E, we performed a randomized controlled trial. METHODS: One hundred and five successive patients with coronary heart disease (CHD) presenting to our centre were recruited and using a Latin-square design divided into 3 groups of 35 each. The groups were matched for age, lifestyle and dietary variables, clinical diagnosis and drug treatment status. None of the patients was on lipid-lowering drugs. Supplemental vitamins were stopped for one month before study began and American Heart Association Step II dietary advice was given to all. At baseline, total cholesterol, triglycerides, HDL and LDL cholesterol and lipid peroxide estimated as thiobarbituric acid reactive substances (TBARS) were determined. Group I received placebo capsules; Group II vitamin E capsules 400 units/day; and Group III received finely pulverized T. arjuna tree bark-powder (500 mg) in capsules daily. Lipids and lipid peroxide levels were determined at 30 days follow-up. RESULTS: Response rate in various groups varied from 86% to 91%. No significant changes in total, HDL, LDL cholesterol and triglycerides levels were seen in Groups I and II (paired t-test p > 0.05). In Group III there was a significant decrease in total cholesterol (-9.7 +/- 12.7%), and LDL cholesterol (-15.8 +/- 25.6%) (paired t-test p < 0.01). Lipid peroxide levels decreased significantly in both the treatment groups (p < 0.01). This decrease was more in vitamin E group (-36.4 +/- 17.7%) as compared to the T. arjuna group (-29.3 +/- 18.9%). CONCLUSIONS: Terminalia arjuna tree bark powder has significant antioxidant action that is comparable to vitamin E. In addition, it also has a significant hypocholesterolaemic effect.
Anticholesteremic Agents↗
Comparison of antioxidant efficacy of vitamin E, vitamin C, vitamin A and fruits in coronary heart disease: a controlled trial.
OBJECTIVE: To determine the efficacy of various antioxidant vitamins and a major dietary source of antioxidants (fruits) we performed a randomized controlled trial. METHODS: 175 successive patients with coronary heart disease (CHD) presenting to our centre were recruited and using a Latin-square design divided into five groups of 35 each. The groups were matched for age, lifestyle and dietary variables, clinical diagnosis and drug treatment status. None of the patients was on lipid-lowering drugs. Supplemental vitamins were stopped for one month before study began and American Heart Association Step II dietary advice was given to all. At baseline, total cholesterol, triglycerides, HDL and LDL cholesterol and lipid peroxide measured as thiobarbaturic acid reactive substances (TBARS) were determined. Group I received placebo capsules; Group II vitamin E 400 units/day; Group III vitamin C 1,000 mg; Group IV vitamin A 25,000 IU; Group V received 400 gm of fruit daily. Lipids and lipid peroxide levels were determined at 30 days follow-up. RESULTS: Response rate in various groups varied form 86% to 91%. No significant changes in total, HDL, LDL cholesterol and triglyceride levels were seen in Groups I, II, III and IV (paired t-test p > 0.05). In Group V there was a significant decrease in total cholesterol (-7.8 +/- 11.1%), and LDL cholesterol (-11.2 +/- 25.4%) and increase in HDL cholesterol (+12.9 +/- 20.1%) (paired t-test p < 0.01). Lipid peroxide levels decreased significantly in all the treatment groups (p < 0.01). This decrease was the highest in Group II (vitamin E; -36.4 +/- 17.7%) as compared to Group III (vitamin C -19.8 -/+ 10.8%); Group IV (vitamin A -5.4 +/- 17%) and Group V (fruits -13.1 +/- 12.0%). CONCLUSIONS: All the antioxidant vitamins and fruits significantly decrease lipid peroxide levels and oxidant load in CHD patients. However, fruits are the best choice as they also favourably modify the lipid profile.
Antioxidants↗
Right-sided non-bacterial thrombotic endocarditis in a chronic hemodialysis patient with Muir-Torre syndrome.
Endocarditis is a recognised complication ofhemodialysis. This is generally only thought of in terms of infective vegetations. We present a case of right-sided NBTE in a patient with an indwelling venous catheter who also had advanced pelvic malignancy. The unusual side of this patient's endocarditic lesions implicates a role for the venous catheter in determining the site of non-bacterial thrombus formation. It is also a reminder that endocarditis is always a risk when using central venous catheters, even after appropriate sterile precautions have been taken.
Adult↗
Direct visualization and quantitation of cytomegalovirus-specific CD8+ cytotoxic T-lymphocytes in liver transplant patients.
BACKGROUND: CMV infection remains a significant clinical problem in the context of LT. Changes in the magnitude of the CMV-specific CTL response after LT have not previously been assessed but may be important in determining the outcome of CMV infection. METHOD: We used a fluorescent HLA-B*0702-CMV peptide tetrameric complex to directly visualize and quantitate CMV-specific CD8+ CTL both in immunosuppressed patients after LT and in immunocompetent controls. RESULTS: CMV-specific CD8+ CTL, at a frequency ranging from 0.1 to 5.8% of CD8+, were detected in the peripheral blood of 22 of 25 B*0702, CMV immunoglobulin G seropositive individuals, with no difference observed between immunocompetent controls and patients >3 years after LT. In CMV seropositive LT recipients who did not have symptomatic CMV infection during the first 3 months after LT, CMV-specific CD8+ CTL magnitude initially decreased, then increased up to 5 times higher than pre-LT levels within 3 months. Two CMV seronegative recipients of seropositive donors had symptomatic CMV infection in association with high viral load. In both patients, no CD8+ CTL response was detected before the onset of symptoms, and a reduction in viral load was observed during antiviral therapy. However, polymerase chain reaction negativity was achieved only when a demonstrable CMV-specific CD8+ CTL response was generated. Responses were never observed in asymptomatic CMV seronegative patients. CONCLUSIONS: We suggest that the generation of CMV-specific CD8+ CTL may be driven by, and seems to coincide with the suppression of, viral reactivation. Direct monitoring of CMV-specific CD8+ CTL using an HLA-peptide tetramer may prove to be of value in the management of patients after LT.
Blood↗
Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants.
Incidences of and risk factors for Streptococcus pneumoniae sepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P =.03) and chronic GVHD (10-year probability, 14% vs 4%; P =.002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127; P =.07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16; P =.04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk. (Blood. 2000;95:3683-3686)
Adolescent↗
Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial.
BACKGROUND: Autologous transplantation with peripheral blood stem cells (PBSC) results in faster haematopoietic-cell repopulation than with bone marrow. We prospectively compared bone marrow and PBSC for allogeneic transplantation. METHODS: Adult HLA-identical sibling donors provided bone marrow and lenograstim-mobilised PBSC. 39 patients with malignant haematological disorders were infused with either bone marrow (n=19) or PBSC (n=20) after standard conditioning regimens in a double-blind, randomised fashion. The identity of the infused products for all patients remained masked until 1 year after the last patient had received transplantation. FINDINGS: The PBSC group had significantly faster neutrophil recovery to 0.5x10(9)/L (median 17.5 vs 23 days, p=0.002), and platelet recovery to 20x10(9)/L (median 11 vs 18 days, p<0.0001) and to 50x10(9)/L (median 20.5 vs 27 days, p=0.02) than the bone-marrow group. PBSC patients were discharged from hospital earlier than were bone-marrow patients (median 26 vs 31 days, p=0.01). At 4 weeks after transplantation, absolute lymphocytes (0.48 vs 0.63, p=0.08) and CD25 cells (0.04 vs 0.08, p=0.007) were higher in the PBSC group, and the proportion of patients with absolute lymphopenia (74% vs 33%, p=0.03) and CD4 lymphopenia (59% vs 24%, p=0.05) was significantly higher in the bone-marrow group. There was no significant difference in the occurrence of acute or chronic graft-versus-host disease and overall survival. The probability of relapse was significantly higher in the bone-marrow group than in the PBSC group (p=0.01); all five relapses occurred among bone-marrow recipients. INTERPRETATION: Our small study indicates that PBSCs are better than bone marrow for allogeneic transplantation from HLA-identical siblings in terms of faster haematopoietic and immune recovery, and have the potential to reduce disease recurrence.
Adult↗
Quantitation of Epstein-Barr virus DNA in the blood of adult liver transplant recipients.
BACKGROUND: Posttransplant lymphoproliferation is most often observed in pediatric transplant recipients who experience primary Epstein-Barr virus (EBV) infection at the time of or after transplantation. Lymphoproliferation is believed to be caused by impaired control of EBV-infected cells, which may be of recipient or donor origin. Most studies of EBV infection and lymphoproliferation have focused on the pediatric age group. METHODS: We have undertaken a prospective study of EBV infection in adult liver transplant recipients. Sequentially collected peripheral blood lymphocytes were examined with a recently developed quantitative polymerase chain reaction assay. The assay quantitates EBV DNA genomic titre over a 5 log10 range. RESULTS: Compared with healthy EBV seropositive people not undergoing immunosuppressive therapy, blood EBV DNA titre is elevated in patients with liver disease before transplantation. Overall, highest titres were observed during the first posttransplant month, and in the context of antilymphocyte therapy. In one patient, lymphoproliferation was associated with high titres which fell during reduction of immunosuppressive therapy. In another patient with lymphoproliferation of donor lymphocyte origin, blood EBV DNA titre was not as high. CONCLUSIONS: EBV proliferation is seen in the context of advanced liver disease and after liver transplantation. EBV DNA quantitation is a useful tool to examine the effects of immunosuppression on EBV-associated lymphoproliferation, and may be an essential technique for programs exploring the merits of EBV adoptive immunotherapy.
Adult↗
Melphalan/TBI is not more carcinogeneic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a period of 26 years.
As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2-17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P < 0.0001). The cumulative overall risk of developing a SMN at 2, 5, 10 and 15 years post transplant was 0.4% (95% CI 0.1-2.6%), 1.7% (95% CI 0.6-4.4%), 6.4% (95% CI 2.8-10.8%) and 6.6% (95% CI 3.4-12.4%), respectively. Even though age-adjusted rates were higher than the general population melphalan/TBI was not associated with higher age-adjusted risk than Cy/TBI (increased risk 7.9 vs 11.4; P = NS). The cumulative overall risk of SMNs was not different with CY/TBI or Mel/TBI (8/393 vs 4/363; 10 year risk 4.4%, 95% CI 1.8-10.6 vs 8.4%, 95% CI 2.9-22.9; P = NS). The risk was significantly higher with use of additional cranial or cranio-spinal irradiation (17.5% vs 2.7% at 10 years; P = 0.0241). Transplants for acute lymphatic leukaemia resulted in a higher incidence of SMNs than did transplants for other diseases (ALL: 17.4%, 95% CI 6.3-42.6%; other diseases: 3.4% (95% 1.3-8.5%, P = 0.0469). The risk of SMN for patients with chronic GVHD was 8.4% (95% CI 3.7-18.7%) as compared to 3.5% (95% CI 1-11.1%) for patients without chronic GVHD (P = NS). No factor was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI.
Adolescent↗
Melphalan plus total body irradiation (MEL-TBI) or cyclophosphamide (MEL-CY) as a conditioning regimen with second autotransplant in responding patients with myeloma is inferior compared to historical controls receiving tandem transplants with melphalan alone.
The role of more intense conditioning for second transplant was evaluated in myeloma patients achieving at least partial remission (PR) after first transplant with melphalan at 200 mg/m2. Forty-three patients received more intensive conditioning for the second transplant. Nineteen patients received cyclophosphamide 120 mg/kg along with melphalan 200 g/m2 (MEL-CY; group 1) while 24 patients received total body irradiation (1125 cGy) in conjunction with melphalan 140 mg/m2 (MEL-TBI; group 2). Forty-three matched control patients were identified from 450 patients receiving melphalan alone for second transplant (MEL200; group 3). Engraftment and toxicities were comparable among the groups with the exception of increased treatment-related mortality of 8% in group 2 compared to none in groups 1 and 3 (P = 0.07). Despite identical CR rates of 74, 71 and 70%, respectively, in groups 1, 2 and 3 (P = 1.0), event-free survival (median: 27, 15 and 61; P < 0.0001) and overall survival (median: 39, 25 and 76 months; P = 0.003) were significantly decreased in patients receiving more intensive conditioning (groups 1 and 2). Lymphocyte recovery, evaluated as a surrogate for immune recovery, was inferior in more intensively treated patients (groups 1 and 2 compared to group 3). Our findings suggest that more intense conditioning appears to have no benefit in patients responding to their first cycle of high-dose therapy and may even be detrimental in this setting. Bone Marrow Transplantation (2000) 25, 483-487.
Antigens, CD34↗