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Biomedical subjects

S Singhal

Publications and source records attributed to S Singhal.

At least 145 records · Page 8Linked to original sources
PubMed1996

Idarubicin, high-dose cytarabine, and etoposide for induction of remission in acute leukemia.

Between 1990 and 1944, 52 newly diagnosed patients with primary (n = 47) or therapy-related (n = 5) acute myeloid leukemia (AML) under the age of 55 years received an induction chemotherapy protocol (designated BF12) consisting of idarubicin ([IDA] 5 mg/m2), high-dose cytarabine ([HD-Ara-C] 2 mg/m2 per 12 hours, 3-hour infusion), and etoposide ([VP-16] 100 mg/m2, 1-hour infusion) on each of 5 consecutive days. Thirty-seven of 51 assessable patients (72.5%), including all five patients with therapy-related AML, attained remission with one cycle. The overall remission rate was 78.4%. Total therapy of AML, with BF12 followed by two courses of consolidation therapy and allogeneic or unpurged autologous bone marrow transplantation (BMT) in first remission, has resulted in actuarial 3-year survival of 49.9% of consecutive unselected patients with newly diagnosed primary AML (minimum follow-up period, 1 year). Twenty-five patients have received BF12 for relapsed acute leukemia, including 13 relapsing after BMT. Five patients died of toxicity and were not assessable for response. Of the remaining 20 patients, five were refractory, two attained partial remissions, and 13 (65%) achieved complete remission (CR). Four of the 13 patients relapsing after BMT died of toxicity, four were refractory, and five of nine assessable patients (56%) attained CR. We conclude that the combination IDA/HD-Ara-C/VP-16 is highly effective in the treatment of newly diagnosed AML and relapsed acute leukemia.

Acute Disease↗
PubMed1996

Role of CD34+ cells in engraftment after high-dose melphalan in multiple myeloma patients given peripheral blood stem cell rescue.

During the period December 1992 to June 1995, 95 patients were treated with high-dose melphalan (HDM) with peripheral blood stem cell rescue (PBSCR). Sixty-five had received previous treatment and 28 had relapsed. Among patients who had relapsed 21/28 had received HDM previously including one who received HDM twice during the course of the study. Seventy-five patients were given HDM/PBSCR for the first time. Comparisons have been made between engraftment times for platelets and neutrophils among patients who received less than or greater than 2 x 10(6) CD34+ cells at rescue. Analyses have also been done to evaluate the effect of previous HDM on recovery. Mobilization of progenitor cells was done with granulocyte colony-stimulating factor (G-CSF). Patients received only PBSCR. No growth factors were given to the PBSCR recipients during the recovery period. The percentage of patients from whom the number of CD34+ cells mobilized was > 2 x 10(6)/kg was similar in patients who received HDM for the first time (23%) compared with those who had had it previously (19%). The yield of CD34+ cells correlated with the number of granulocyte-macrophage colony forming units (CFU-GM). Although the number of CD34+ cells infused was < 2 x 10(6)/kg in 77% of patients, all engrafted for neutrophils to > 0.5 x 10(9)/l. This was delayed in patients who had had previous HDM (P < 0.02). Platelet recovery to > 25, 50 and 100 x 10(9)/l was delayed in all patients who received < 2 x 10(6) CD34+ cells/kg infused (P < 0.02). In patients who had had previous HDM both neutrophil (P < 0.05) and platelet recovery (P < 0.007) were delayed compared with recovery in patients who had not had HDM. In patients who had had previous HDM and received < 2 x 10(6) CD34+ cells/kg infused only 3/17 regained platelets to > 100 x 10(9)/l compared with 3/4 who had > 2 x 10(6) CD34+ cells/kg infused (P < 0.05 Fisher's exact test). There was no evidence that low numbers of CD34+ cells in the PBSCR were associated with early death. The data show that previous treatment with HDM had adverse effects on the subsequent engraftment of platelets among patients given HDM/PBSCR. The data suggest that additional measures are needed to achieve platelet reconstitution in these heavily pre-treated patients.

Antigens, CD34↗
PubMed1996

Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility in women.

Melphalan has rarely been used as a single agent for conditioning prior to allogeneic marrow transplantation. Twenty-eight patients (median age 19.5 years) undergoing allogeneic BMT for acute leukemia (n = 26) or lymphoblastic lymphoma (n = 2) in first remission (n = 10) or beyond (n = 18) from HLA-identical siblings received 240 mg/m2 melphalan. Death due to primary graft failure was seen in two patients. Sustained hematopoietic recovery was seen in all the others (n = 22) not dying early due to toxicity (n = 2) or persistent active disease (n = 2). The 3-year probabilities of transplant-related mortality and relapse were 35% and 62%, respectively. Seven patients are alive and well at 103-163 months (median 136) with Karnofsky scores of 100% (10-year disease-free survival, 25%). Of the 16 patients with donors of the opposite sex, seven underwent cytogenetic studies after BMT and showed complete chimerism with donor cells. Amongst the four women who were 15-30 years at the time of the transplant, there were seven pregnancies over 297 months of follow-up beyond 2 years from transplant. In contrast, no pregnancies were seen in 53 women with hematologic malignancies who were conditioned with other regimens over 3524 months of follow-up beyond 2 years from transplant. The pregnancy rate was significantly higher (P < 0.001) for women conditioned with melphalan alone (three of four) than for those conditioned with other regimens (0 of 53). We conclude that pre-transplant conditioning with melphalan alone permits alloengraftment of marrow from HLA-identical siblings, and may preserve fertility better than other regimens in some women.

Adolescent↗
PubMed1995

Relationship between donor-recipient blood group incompatibility and serum bilirubin after allogeneic bone marrow transplantation from HLA-identical siblings.

Data on 477 patients with hematologic malignancies undergoing allogeneic bone marrow transplantation from HLA-identical siblings were analyzed for correlation between donor-recipient ABO blood group incompatibility and the development of elevated bilirubin levels (over 17 mmol/l) after transplantation. The median bilirubin on day 15 after transplant and the maximum bilirubin in the first 100 days were significantly higher in 155 patients with ABO-mismatched donors compared with 322 patients with ABO-matched donors. In univariate analysis, age > 16 years (P = 0.000006), ABO incompatibility (P = 0.0004), a conditioning regimen other than cyclophosphamide-total body irradiation (P = 0.0005) and a diagnosis other than acute leukemia (P = 0.01) were associated with a higher probability of developing elevated bilirubin. Incidence of clinically diagnosed graft-versus-host disease (GVHD), and transplant-related mortality, relapse rates and overall survival were not influenced by ABO incompatibility. The hyperbilirubinemia was therefore unlikely to be the result of an increased incidence of hepatic complications such as GVHD or veno-occlusive disease. We suggest that studies on serious transplant-related complications such as GVHD and veno-occlusive disease which rely on bilirubin values for diagnosis should take donor-recipient ABO incompatibility into account.

Adolescent↗
PubMed1995

Cytokine-mediated immunotherapy with or without donor leukocytes for poor-risk acute myeloid leukemia relapsing after allogeneic bone marrow transplantation.

Six patients with high-risk acute myeloid leukemia (AML) relapsing after allogeneic bone marrow transplantation (BMT) were treated with interferon-alpha 2b to stimulate graft-versus-leukemia reactions. Additionally, donor mononuclear cells were infused with or without interleukin-2 as first-line treatment or upon failure of interferon-alpha 2b in 5 patients. Two patients developed clinical acute graft-versus-host disease (GVHD) after a combination of donor leukocytes and interferon-alpha, and one developed de novo chronic GVHD after interleukin-2 and interferon-alpha. Complete remission was attained in 4 patients whereas 2 patients showed no response. Two of the responding patients relapsed rapidly. Four patients died of a combination of complications of immunotherapy and progressive disease. Two patients are alive in remission with chronic GVHD (Karnofsky performance scores of 80%) 8 and 18 months after immunotherapy. We conclude that cytokine-mediated immunotherapy with or without donor cell infusions may be effective in some cases of AML relapsing after allogeneic BMT, and may result in long-term survival. With limited data, it appears that development of chronic GVHD after immunotherapy is essential for continued remission.

Acute Disease↗
PubMed1995

Autologous bone marrow or peripheral blood stem cell transplantation followed by maintenance chemotherapy for adult acute lymphoblastic leukemia in first remission: 50 cases from a single center.

The aim of this study was to evaluate the use of maintenance chemotherapy after autotransplantation in adult acute lymphoblastic leukemia (ALL), and to compare the relative durability of marrow and peripheral blood stem cell grafts to chemotherapy. Fifty consecutive ALL patients received 200 mg/m2 melphalan alone or 110 mg/m2 melphalan with total-body irradiation in first remission, followed by autologous marrow (ABMT, n = 38) or peripheral blood stem cells (PBSCT, n = 12). After hematologic recovery, 6-mercaptopurine and methotrexate were administered for 2 years. 6-mercaptopurine could be given to 78.9% of ABMT recipients at a median daily dose of 33.5 mg/m2, and to 91.7% of PBSCT recipients at a median daily dose of 44.1 mg/m2. ABMT recipients started 6-mercaptopurine at a median of 58.5 days post-transplant, and PBSCT recipients at 32 days (P = 0.002). 52.6% of ABMT recipients and 75% of PBSCT recipients received weekly methotrexate. No graft failure was seen as a result of chemotherapy. The actuarial 5-year probabilities of overall survival, survival in first remission and relapse were 56.2, 53.2, and 30.6%, respectively. We conclude that administration of maintenance chemotherapy after autografting in adult ALL may reduce relapse. A randomized study is required to evaluate the relative efficacy of PBSCT vs ABMT, and the role of post-transplant maintenance chemotherapy.

Adolescent↗
PubMed1995

Three weeks of ganciclovir for cytomegaloviraemia after allogeneic bone marrow transplantation.

Cytomegaloviraemia diagnosed by early antigen detection or conventional viral culture from blood occurred 7-71 days (median 41 days) after transplant in 25 of 38 consecutive patients undergoing bone marrow transplantation (BMT) from HLA-identical siblings for haematological malignancies where patient and/or donor were CMV-seropositive. Prophylactic ganciclovir, high-dose intravenous acyclovir or immunoglobulin were not administered. Viraemia was treated with a short 3-week course of ganciclovir (10 mg/kg x 1 week, 5 mg/kg x 2 weeks). Clearance of viraemia occurred 3-47 days (median 6 days) after starting anti-viral therapy in 20 patients (18 with ganciclovir, 2 with foscarnet), and before therapy in 3 patients. The remaining 2 patients received inadequate anti-viral therapy for various reasons and died of CMV pneumonitis. There was no clinical evidence of CMV disease in the 13 patients who did not develop viraemia. One patient treated with ganciclovir before adequate haematological recovery died of graft failure. A second episode of viraemia occurred in four patients, and a third in one. We conclude that a short 3-week course of ganciclovir is adequate in most patients developing cytomegaloviraemia after allogeneic BMT. Treatment is not necessary in all patients but some inadequately treated patients develop CMV disease. Ganciclovir is tolerated well but may cause severe myelosuppression if used prior to adequate marrow recovery.

Adolescent↗
PubMed1995

Maintenance therapy for remission in myeloma with Intron A following high-dose melphalan and either an autologous bone marrow transplantation or peripheral stem cell rescue.

Eighty-four patients with myeloma were randomized to receive maintenance Intron A (Schering-Plough, Suffolk, UK), 3 mega units/m2 s.c. three times weekly or no treatment following induction therapy with cyclophosphomide, vincristine, doxorubicin, methyl prednisolone (C-VAMP), consolidated with high-dose melphalan (HDM) 200 mg/m2 + autologous bone marrow transplantation (ABMT). The patients have been followed up for a median of 52 months. Overall, median progression-free survival (PFS) from HDM was 27 months in the control group and 46 months in the Intron A group (< 0.025). For the 65 patients who achieved complete remission (CR) with HDM, there was a significant prolongation of remission (p = 0.02) for those who received Intron A and 49% of these patients remained in remission four years after high-dose treatment. However, for partial responders (PR) and nonresponders to HDM there was no significant prolongation of PFS. Overall, survival was also significantly better for the Intron A group, with 5 deaths versus 14 deaths in the control group (p = 0.006). Subsequently, 54 consecutive patients received the same HDM followed by rescue with peripheral blood stem cells after induction chemotherapy which included C-VAMP. Intron A was started in 45 of these patients at a median of 62 days which was comparable to the ABMT arm. The overall response rate in these patients was 79.62% (43/54-CR+PR) and the probability of survival at 18 months was 74.2% by the Kaplan Meier method.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Autologous bone marrow transplantation for acute myeloid leukemia in first remission: identification of modifiable prognostic factors.

Seventy-four consecutive patients (median age 31 years) with acute myeloid leukemia (AML) undergoing unpurged autologous bone marrow transplantation (ABMT) in first remission after melphalan and total-body irradiation were studied to assess the impact of 14 modifiable and non-modifiable prognostic factors on relapse and disease-free survival. Thirty patients were alive in continuous CR at a median of 37.5 months (range 3-94), 14 died of transplant-related toxicity at a median of 5.5 months (range 0.5-18), and 30 relapsed at a median of 7.5 months (range 2-23). The actuarial 5-year probabilities of relapse and disease-free survival were 53.4 and 34.2%, respectively. On multivariate analysis, administration of two or more courses of consolidation chemotherapy prior to the harvest and transplant was found to be the most significant factor associated with decreased relapse (relative risk 2.62, P = 0.0012) and improved disease-free survival (relative risk 3.03, P = 0.0009). A nucleated cell dose of > 2 x 10(8)/kg improved disease-free survival (relative risk 2.17, P = 0.045) by decreasing transplant-related mortality (P = 0.047). We conclude that adequate consolidation of remission before ABMT is the most important factor associated with continuing remission after ABMT. Short-term therapy of AML with two courses of consolidation therapy followed by ABMT requires comparison with repeated courses of intensive chemotherapy for efficacy and cost-effectiveness.

Adolescent↗
PubMed1995

Kinetics of paraprotein clearance after autografting for multiple myeloma.

The kinetics of paraprotein clearance after autografting for multiple myeloma have not been described. We studied 33 myeloma patients in plateau phase with detectable paraprotein (3-34 milligrams, median 10 milligrams) at the time of ABMT who received melphalan (200 mg/m2) and methylprednisolone (1.5 g x 5) for conditioning. Fifteen patients received interferon-alpha post-transplant as part of a randomized study. Twenty-four of 33 (72.7%) patients eventually cleared the paraprotein at a median of 47 days (range 5-783) post-transplant. The probability of clearance was lower (46.7 vs 94.4%, P = 0.004) and the time taken to clear paraprotein longer (142 vs 29 days, P = 0.003) in patients with a higher level (> 10 milligrams) at the time of the transplant. However, clearance occurred within 6 months in 23 of 24 (95.8%) patients who ultimately cleared the paraprotein. Interferon-alpha did not influence the clearance of paraprotein. We conclude that after autografting for myeloma, the time taken to clear paraprotein is longer and the probability of clearance lower with higher levels at the time of ABMT, and most patients who eventually clear the paraprotein do so within 6 months. Because the probability of clearing paraprotein (and thus attaining remission) in patients with detectable paraprotein 6 months post-transplant is low, a decision about further treatment may be made at this point.

Adult↗
PubMed1995

Comparison of Cobe Spectra and Haemonetics MCS-3P cell separators for peripheral blood stem cell harvesting.

A prospective study was undertaken to compare the total nucleated cell (TNC), mononuclear cell (MNC), CD34+ cell, and CFU-GM yields of two different cell separators. A Haemonetics MCS-3P and a Cobe Spectra machine were used to leukapherese 10 patients with malignant diseases on 4 consecutive days after mobilization with G-CSF. All patients were harvested twice on each machine for a fixed period of time. The blood volume processed (10.47 vs 3.79 l, P < 0.001), MNC yield (2.66 vs 0.90 x 10(8)/kg; P < 0.001), MNC yield rate (1.66 vs 0.55 x 10(6)/kg/min; P < 0.001), MNC purity (81 vs 42%; P < 0.001), CFU-GM yield (18.1 vs 5.5 x 10(4)/kg; P = 0.001), and CFU-GM yield rate (11.27 vs 3.42 x 10(2)/kg/min; P = 0.001) were significantly higher with the Spectra. The CD34+ cell yields and yield rates were comparable. Although CFU-GM and MNC yields per unit blood volume processed were comparable for both machines, there was a trend for higher CD34+ yields per unit volume processed with MCS-3P. We conclude that Spectra is faster than MCS-3P with more blood processed per unit time resulting in higher cell yields, but yields per unit volume processed are comparable for both machines. The choice of machine for a given patient depends upon convenience, venous access and the time available.

Adult↗
PubMed1995

Allogeneic bone marrow transplantation for primary myelofibrosis.

The published experience of allogeneic bone marrow transplantation for primary myelofibrosis (PMF) is limited. Three patients (24-49 years) with PMF received allogeneic marrow grafts from HLA-identical sibling donors after conditioning with 110 mg/m2 melphalan and 1050 cGy total-body irradiation (TBI). Donor marrow was not depleted of T cells, and graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine and methotrexate. None of the patients was splenectomized prior to the transplant. Two patients received G-CSF post-transplant to hasten neutrophil recovery. One patient died of multi-organ failure 23 days post-transplant. Hematopoietic recovery was relatively slow in the other two who had gradual resolution of the marrow fibrosis over several months. One of the two died of overwhelming pneumococcal sepsis within 2 weeks of stopping prophylactic penicillin 31 months post-transplant. The other patient is alive and well 20 months post-transplant with a Karnofsky score of 100% and no fibrosis of the marrow. We conclude that PMF is correctable by allogeneic BMT. Hematologic recovery post-transplant is slow, but counts may normalize with time without the need for splenectomy.

Adult↗