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J Mehta

Publications and source records attributed to J Mehta.

At least 37 records · Page 2Linked to original sources
PubMed1998

Identification of new nonrandom translocations in multiple myeloma with multicolor spectral karyotyping.

Multicolor spectral karyotyping (SKY) was performed on bone marrow samples from 50 patients with multiple myeloma (MM) in anticipation of discovering new previously unidentified translocations. All samples showed complex karyotypes with chromosome aberrations which, in most cases, were not fully characterized by G-banding. Patients of special interest were those who showed add(14)(q32), add(8)(q24) and those whose G-banding karyotypes showed poor chromosome morphology. Three new recurring chromosome translocations not previously reported in MM were identified. Two of the translocations involve recurring aberrations at band 14q32.3, the site of the IgH locus, with different exchange partners. The most frequently recurring rearrangement was a subtle translocation at 14q32.3 designated as a t(14;16)(q32;q22 approximately 23), which was identified in six patients. A second and larger translocation at 14q32, identified in two patients, was designated as a t(9;14)(p13;q32), previously associated with Waldenstrom's macroglobulinemia and lymphoplasmacytoid lymphoma. A third translocation, identified in two patients, involved a whole-arm t(6;8)(p10;q10) translocation. The SKY technique was able to refine the designations of over 156 aberrations not fully characterized by G-banding in this study and resolved additional chromosome aberrations in every patient studied except two. The t(14;16)(q32;q22 approximately 23) identified by SKY in this study suggests this may be a frequent translocation in MM associated with complex karyotypes and disease progression. Therefore, the SKY technique provides a useful adjunct to routine G-banding and fluorescence in situ hybridization studies in the cytogenetic analysis of MM.

Chromosomes, Human, Pair 14↗
PubMed1998

Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation.

Two hundred and one patients (median age, 29 years) with acute myeloid leukemia (AML) underwent bone marrow transplantation (BMT) from HLA-identical sibling donors after conditioning with melphalan-total-body irradiation (TBI) (57%), cyclophosphamide-TBI (35%), or chemotherapy alone (8%). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine alone (68%), cyclosporine-methotrexate (26%), or T-cell depletion (6%). The probability of relapse was calculated as a function of the absolute lymphocyte count (10(9)/L) on days 27 to 30 posttransplant (<0.1 v >/=0.1, <0.2 v >/=0.2, and <0.3 v >/=0.3). In each of these 12 comparisons, the probability of relapse was higher for the group with the lower lymphocyte count. Because the difference was most significant (P = .004) for an absolute lymphocyte count of <0.2 on day 29 (3-year relapse probability, 42%) versus >/= 0.2 (16%), this variable was included in a Cox model to determine factors independently affecting relapse. Multivariate analysis showed that conditioning regimens other than melphalan-TBI, a low lymphocyte count on day 29, French-American-British (FAB) subtypes M4-7, and a nucleated cell dose of > 2.42 x 10(8)/kg was associated with a higher risk of relapse. We conclude that slow lymphocyte recovery after allogeneic BMT, to < 0.2 x 10(9)/L 29 days in this analysis, appears to be associated with a higher risk of relapse in patients with AML. This group of patients may benefit from posttransplant immune manipulations such as abbreviated GVHD prophylaxis, or donor cell or cytokine administration to enhance graft-versus-leukemia reactions to reduce relapse.

Acute Disease↗
PubMed1998

Salvage autologous or allogeneic transplantation for multiple myeloma refractory to or relapsing after a first-line autograft?

Forty-two patients allografted for multiple myeloma after not having attained at least a partial remission (n = 19) or after having experienced disease progression (n = 23) following one autograft were compared with 42 pair-matched controls who underwent salvage autotransplantation under identical conditions. Autografted controls were matched closely for albumin, C-reactive protein, creatinine, disease sensitivity, duration of standard therapy prior to the first transplant, Ig isotype, karyotype, LDH, and response to the first transplant, but, in comparison to allografted patients, were older, had higher beta2-microglobulin, and had a shorter interval between the two transplants. The complete remission rate was 41% after allogeneic and 33% after autologous transplantation (P = NS). The 3-year probability of event-free survival was comparable for the two groups (25 +/- 8% after autografting and 20 +/- 8% after allografting). The 3-year probability of survival was significantly higher after autologous transplantation (54 +/- 8% vs 29 +/- 9%; P = 0.01). Twenty-one patients in the autograft group were alive 11-59 months (median 32) following the second transplant, while 15 patients in the allograft group were alive at 10-53 months (median 20). The 3-year probability of disease progression was significantly lower after allogeneic transplantation (31 +/- 10% vs 72 +/- 9%, P = 0.03). The 1-year probability of transplant-related mortality was significantly higher after allografting (43 +/- 8% vs 10 +/- 5%; P = 0.0001). We conclude that while autografting appears to be superior to allografting for salvage therapy of myeloma persisting or relapsing after one previous autotransplant in terms of overall survival, event-free survival is comparable due to significantly lower disease progression after allografting. Reduction in allograft-related toxicity can potentially improve the results of allogeneic transplantation significantly.

Adult↗
PubMed1998

Graft-versus-myeloma after donor leukocyte infusion: maintenance of marrow remission but extramedullary relapse with plasmacytomas.

Adoptive immunotherapy with donor leukocytes has emerged as a promising strategy for the treatment of myeloma recurrence after allogeneic transplantation. 2.9 x 10(8)/kg donor mononuclear cells containing 1.4% CD34+ and 37% CD3+ cells were administered to a 48-year-old patient with non-secretory plasmablastic myeloma relapsing 9 months after a blood stem cell transplant from his HLA-identical sibling. In view of the extensive marrow infiltration and the aggressive behaviour of the disease, the donor cells were preceded by a course of EDAP chemotherapy. There was rapid clinical improvement, and CR was achieved on day 30 post infusion. However, three subcutaneous plasmacytomas showing anaplastic features developed within a few days. These failed to respond to interferon-alpha and continued to grow for 5 weeks in the absence of marrow plasmacytosis or other evidence of systemic disease. Grade 3 acute liver GVHD developed on day 79 which was controlled with immunosuppression. Overt systemic relapse occurred on day 90 as the GVHD came under control. The course of our case suggests highly proliferative malignant cells may escape the graft-versus-tumour effect of immunocompetent allogeneic cells in extramedullary sites subsequently resulting in overt systemic relapse if left untreated. New approaches are needed to deal with the problem of extramedullary disease recurrence.

Bone Marrow↗
PubMed1998

Red cell fragmentation (schistocytosis) after bone marrow transplantation.

Red cell fragmentation is often the earliest sign of thrombotic microangiopathy. Days +14, +28 and +42 blood films from 58 allograft and 32 autograft recipients were reviewed blind to determine the incidence and severity of schistocytosis (the number of fragmented red cells per 1000 red cells expressed as a percentage). Schistocytosis was graded as mild (<1%), moderate (1-1.9%) or severe (> or =2%). Schistocytes were seen in 99% of day 14 films (0.1-3.0%, median 0.4%), 97% of day 28 films (0.1-3.2%, median 0.4%), and 98% of day 42 films (0.1-4.3%, median 0.5%). Nine patients (10%) had severe fragmentation and 20 patients (22%) had moderate fragmentation at some time or the other. The difference in the extent of fragmentation between the days was not significant. Allogeneic BMT was associated with more extensive fragmentation than autologous transplantation on day 28 (P = 0.008) and day 42 (P = 0.02). Age, conditioning regimen and diagnosis had no influence. None of the patients followed-up for 6 months after transplant developed full-blown thrombotic microangiopathy. The occasional patient showing mild clinical and laboratory features of hemolysis responded well to adjustment of fluid balance and cyclosporine dose where applicable. Our data indicate that mild red cell fragmentation is a common morphologic finding after transplantation with no clinical significance in the absence of other clinical and laboratory findings suggestive of thrombotic microangiopathy, although patients with moderate or severe fragmentation should be monitored closely.

Adolescent↗
PubMed1998

Graft-versus-myeloma.

Whereas patients with multiple myeloma continue to relapse after autologous transplantation and are unlikely to be cured, the probability of progression is less after allogeneic transplantation and a proportion of patients may be cured. This is attributable to an immunologically mediated graft-versus-myeloma (GVM) effect which is akin to the well-known graft-versus-leukemia effect. The available clinical and experimental evidence strongly support the existence of GVM, but it is not known whether GVM is separable from graft-versus-host disease (GVHD) in practice. The best way to exploit GVM reactions is unclear, and the morbidity and mortality associated with GVHD undermine long-term survival. There is usually a time lag of a few weeks between immune intervention and disease response. There is a propensity for extramedullary disease recurrence in patients whose marrow disease is controlled with immunologic manipulation. Exploration of GVM outside conventional allogeneic transplantation or after autologous transplantation is necessary to increase the number of patients likely to benefit from this phenomenon and to make it safer. This article reviews the currently available literature on the subject.

Bone Marrow Transplantation↗
PubMed1998

Familial acute myeloid leukaemia: four male members of a single family over three consecutive generations exhibiting anticipation.

A kindred with familial acute myeloid leukaemia (AML) is described displaying the concept of anticipation which refers to increased disease severity and/or earlier age at onset with succeeding generations. The affected individual in the first generation was the father (aged 34 years at diagnosis) of two affected members of a single sibship (aged 24 and 25 years). The fourth patient is the son (aged 4 years) of one of these brothers in the second generation. The AML was of different subtypes and a karyotypic abnormality (del[6q]) was detected in one of three patients. The first-generation patient died during chemotherapy; the remaining three patients are in complete remission after chemotherapy and autologous bone marrow transplantation.

Acute Disease↗
PubMed1998

Anti-myeloma activity of pamidronate in vivo.

Two patients with progressive myeloma were treated with pamidronate disodium every 2-4 weeks. Pamidronate therapy resulted in a significant reduction of marrow plasmacytosis and plasma cell labelling index (PCLI), together with durable (> or = 20 months) stabilization of immunoglobulin (Ig) levels and an increase in bone mineral density in the first patient and > 50%, reduction in Ig levels and bone marrow plasmacytosis in the second. This, to our knowledge, is the first report of an anti-myeloma effect of bisphosphonates in humans and provides evidence that a therapeutic intervention largely directed at the myeloma microenvironment may alter the natural history of the disease.

Aged↗
PubMed1998

Comparable engraftment kinetics following peripheral-blood stem-cell infusion mobilized with granulocyte colony-stimulating factor with or without cyclophosphamide in multiple myeloma.

PURPOSE: To compare, in the setting of tandem autotransplantations for multiple myeloma (MM), two established methods of peripheral-blood stem-cell (PBSC) procurement with chemotherapy or hematopoietic growth factor alone. PATIENTS AND METHODS: Between June 1994 and July 1995, 44 patients with MM were randomized to PBSC mobilization with either granulocyte colony-stimulating factor (G-CSF) 16 microg/kg (group 1; n = 22) or high-dose cyclophosphamide (HDCTX) 6 g/m2 plus G-CSF 5 microg/kg (group 2; n = 22). All 44 patients received melphalan 200 mg/m2 with their first autograft and 32 patients proceeded to a second transplantation. RESULTS: Group 2 required a significantly longer time interval for completion of PBSC collection than group 1 (median, 22 v 8 days; P = .0001), greater frequency of hospitalization (100% v 32%; P = .0001), and increased transfusion of platelets (86% v 18%; P = .0001) and packed RBCs (86% v 55%; P = .02). Likewise, the incidence of fever and pneumonia/sepsis were higher in group 2 (P = .02 and P = .04, respectively). Surprisingly, despite greater CD34 cell quantities infused in group 2, median recovery times of granulocytes (both > 500/microL and 2,500/microL) and platelets (both > 50,000/microL and > 100,000/microL) were similar (all P > .7). Posttransplant toxicities were also similar. CONCLUSION: Compared with HDCTX plus G-CSF, high-dose G-CSF alone is associated with lower morbidity, shorter duration of PBSC mobilization, and comparable hematopoietic recovery after transplantation, which should result in significant cost reduction. Considering the relatively limited antitumor activity of HDCTX (10% with > or = 50% tumor cytoreduction), PBSC mobilization with HDCTX should be limited to selected patients with persistent MM despite induction chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Intake of antioxidants among American cardiologists.

A survey of 181 cardiologists was conducted to determine their coronary artery disease (CAD) risk profile and their intake of antioxidants. The survey reflected that the prevalence of CAD risk factors increases with age, as does the prophylactic intake of antioxidants (vitamin E was greater than vitamin C, and vitamin C was greater than beta carotene).

Adult↗
PubMed1997

Prospective, concurrent comparison of the Cobe Spectra and Haemonetics MCS-3P cell separators for leukapheresis after high-dose filgrastim in patients with hematologic malignancies.

A prospective study was undertaken to compare the mononuclear cell, CD34+ cell, and CFU-GM yields of the Haemonetics MCS-3P and the Cobe Spectra cell separators in ten patients (nine multiple myeloma and one non-Hodgkin lymphoma) on two consecutive days after mobilization with high-dose filgrastim (12-16 micrograms/k) for 4 days. All patients were harvested once on each machine, five starting on each machine. The target duration of the procedure on the Spectra was 160 minutes, and the target blood volume processed on the MCS-3P was 60-70 ml/kg body weight. Both machines were operating on the 1995 software versions supplied by the respective manufacturers. The time taken for the procedure was significantly longer with the Haemonetics machine. The volumes of blood processed and the product collected were significantly higher with the Spectra, as were the absolute mononuclear and CD34+ cell yields, and yields per unit time. Mononuclear and CD34+ cell yields per unit volume of blood processed were comparable for both machines. The differences in CFU-GM yields were not significant, largely because of wide interpatient variations. The extent of platelet depletion as a result of the procedure was greater with the Spectra because of the higher blood volume being processed. We conclude that the Cobe Spectra is a significantly faster machine than the Haemonetics MCS-3P; and consequently, its use is associated with higher mononuclear and CD34+ cell yields.

Antigens, CD34↗
PubMed1997

Do variations in molecular structure affect the clinical efficacy and safety of lipid-based amphotericin B preparations?

While amphotericin B is the drug of choice in the treatment of most fungal infections, systemic adverse reactions and dose-dependent nephrotoxicity associated with its use frequently render the conventional preparation of amphotericin unsuitable. A number of lipid-based formulations of amphotericin have been developed to overcome the limitations of the parent compound. These preparations, amphotericin B lipid complex (ABLC), amphotericin B colloid dispersion (ABCD) and liposomal amphotericin differ from one another significantly in their molecular structure. They are also considerably more expensive than the parent compound. Clinical data on their appropriate use are limited. This review looks at the differences in molecular structure of these preparations, and at the available clinical safety and efficacy data.

Amphotericin B↗
PubMed1997

Comparison of marrow vs blood-derived stem cells for autografting in previously untreated multiple myeloma.

Sixty-three new untreated patients with multiple myeloma under the age of 70 years received C-VAMP induction treatment followed by high-dose intravenous melphalan (200 mg m(-2)) and autologous stem cell transplant, either with marrow [autologous bone marrow transplants (ABMT), n = 26] or with granulocyte colony-stimulating factor (G-CSF)-mobilized stem cells from the blood [peripheral blood stem cell transplants (PBSCT), n = 37]. This was a sequential study and the two groups were not significantly different for all known prognostic variables. The complete remission (CR) rate after high-dose treatment was the same for both groups [ABMT 84% and PBSCT 70%; P = not significant (NS)]. Neutrophil recovery to 0.5 x 10(9) l(-1) occurred at a median of 22 days in the ABMT patients compared with 19 days for the PBSCT patients (P = NS). Platelet recovery to 50 x 10(9) l(-1) was significantly faster in PBSCT patients (19 days vs 33 days; P = 0.0015), and the PBSCT patients spent fewer days in hospital (median 20 vs 27 days; P = 0.00001). There was no difference in the two groups with respect to starting interferon (58 days for ABMT vs 55 days for PBSCT), and tolerance to interferon was identical. The median overall survival (OS) and progression-free survival (PFS) for the PBSCT patients has not yet been reached. The OS in the ABMT patients at 3 years was 76.9% (95% CI 60-93%) compared with 85.3% (95% CI 72-99%) in the PBSCT patients (P = NS), and the PFS at 3 years in the ABMT patients was 53.8% (95% CI 34-73%) and in the PBSCT patients was 57.6% (95% CI 34-81%) (P = NS). The probability of relapse at 3 years was 42.3% in the ABMT arm compared with 40% in the PBSCT patients (P = NS). Thus, PBSCT patients had a faster engraftment and a shorter stay in hospital than ABMT; the survival outcome and probability of relapse was the same for both groups.

Adult↗
PubMed1997

Early identification of patients at risk of death due to infections, hemorrhage, or graft failure after allogeneic bone marrow transplantation on the basis of the leukocyte counts.

Allograft recipients are often unwell with significant organ dysfunction by the time delayed or failed engraftment is diagnosed. We attempted to identify factors associated with graft failure, or death due to infection, hemorrhage or graft failure in 712 patients undergoing allogeneic BMT. Low leukocyte counts between days 12 and 22 were strongly associated with subsequent graft failure or death. In multivariate analysis, a leukocyte count of < or = 0.2 x 10(9)/l on day 16 was the most powerful predictor of graft failure or death. Transplants from HLA-mismatched and unrelated donors were also associated with increased risk of both, and T cell depletion with increased risk of graft failure. On the basis of these findings, it may be possible to define graft failure in functional terms as early as 2 weeks after BMT rather than at 3 or 4 weeks. The use of growth factors can then be limited to patients most likely to benefit from them, and it may be possible to salvage patients at risk of complications of low counts early before their clinical condition deteriorates. We suggest that patients with leukocyte counts of 0.2 x 10(9)/l or less 14-16 days after BMT should be started on G-CSF or GM-CSF even if they are clinically well, and consideration should be given to a second infusion of cells.

Adolescent↗
PubMed1997

Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy.

We studied 231 acute leukemia patients relapsing after allogeneic (n = 114) or autologous (n = 117) BMT to assess the outcome of further therapy. In general, all patients in good condition were eligible for second transplants except for post-allograft relapses from 1993-1994 onwards who received cytokine- or cell-mediated immunotherapy. The major reason for patients not progressing to second graft was death from progressive disease or toxicity of salvage chemotherapy. Seventeen of 231 patients (7%) were alive at the last follow-up. Six of 14 post-autograft relapses treated with second transplants were alive and well, compared with five of 103 not undergoing second grafts (P < 0.0001). One of 23 post-allograft recipients treated with second allografts was alive with an extramedullary relapse, compared with five of 13 receiving immunotherapy and none of 78 receiving standard-dose or palliative therapy (P < 0.0001). We conclude that only a small proportion of highly selected acute leukemia patients relapsing after a transplant reach the stage of a conventional second transplant. In our experience, second allografts after myeloablative therapy in patients relapsing after one allograft are associated with very poor results, and immunotherapy may be a better approach in such cases. Selected patients relapsing after an autograft may become long-term survivors following a second autograft or an allograft.

Acute Disease↗
PubMed1997

Sensitivity of secondary acute myeloid leukemia relapsing after allogeneic bone marrow transplantation to immunotherapy with interferon-alpha 2b.

A patient with acute myeloid leukemia secondary to therapy of choriocarcinoma underwent T cell non-depleted allogeneic bone marrow transplantation from an unrelated donor in first untreated relapse. Persistent/relapsed leukemia 4 months after transplantation did not respond to cessation of cyclosporine. Due to logistic difficulties in obtaining donor leukocytes, she was treated with interleukin-2 and interferon-alpha 2b. Although the interleukin could be administered for a short period only, the interferon was continued for 4 months. Interferon was stopped when limited chronic graft-versus-host disease developed, but was followed by extramedullary and early marrow relapse. Reinstitution of interferon resulted in the development of scleroderma-like extensive chronic GVHD and remission. Interferon was given for 5 months. GVHD improved slowly with treatment, but scleroderma-like changes still persist. The patient is alive with no evidence of disease and a Karnofsky score of 90% 41 months after relapse and 26 months after stopping cyclosporine. We conclude that cytokines alone may occasionally result in a durable response of acute leukemia relapsing after allografting, and should be considered in patients with a low tumor burden if it is difficult to obtain donor cells.

Adult↗