Biomedical subjects

M Korbling

Publications and source records attributed to M Korbling.

At least 19 recordsLinked to original sources

PubMed2006

Phase II study of unrelated cord blood transplantation for adults with high-risk hematologic malignancies.

Cell dose is a critical determinant of outcomes in unrelated cord blood (CB) transplantation. We investigated a strategy in which CB units should contain at least 2 x 10(7) total nucleated cells/kg of recipient weight, otherwise a second unit had to be added. We report the results of a study that was prematurely closed owing to toxicity. Patients with advanced hematologic malignancies without a human leukocyte antigen-matched sibling or unrelated donor were eligible. Conditioning regimen consisted of fludarabine and 12 Gy of total body irradiation (n=11), or melphalan (n=4), with antithymocyte globulin. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Fifteen patients with acute leukemia (n=9), chronic myelogenous leukemia (n=2), multiple myeloma (n=2) and lymphoma (n=2) were treated; 60% had relapsed disease at transplantation. Three patients received double CB transplants. The 100-day and 1-year treatment-related mortality rates were 40 and 53%, respectively. Median time to neutrophil and platelet engraftment was 22 days (n=10) and 37 days (n=10), respectively. One patient had secondary graft failure and five patients failed to engraft. Two patients are alive and disease free; 4-year actuarial survival is 33 versus 0% for patients transplanted in remission versus in relapse. We concluded that disease status was the main determinant of treatment failure in this study.

Adult↗

PubMed2004

A mathematical model of haemopoiesis as exemplified by CD34 cell mobilization into the peripheral blood.

A mathematical model for the kinetics of haemopoietic cells, including CD34+cells, is proposed. This minimal model reflects the known kinetics of haemopoietic progenitor cells, including peripheral blood CD34+ cells, white blood cells and platelets, in the presence of granulocyte colony-stimulating factor. Reproducing known perturbations within this system, subjected to granulocyte colony-stimulating factor treatment and apheresis of peripheral blood progenitor cells (CD34+ cells) in healthy individuals allows validation of the model. Predictions are made with this model for reducing the length of time with neutropenia after high-dose chemotherapy. Results based on this model indicate that myelosuppressive treatment together with infusion of CD34+ peripheral blood progenitor cells favours a faster recovery of the haemopoietic system than with granulocyte colony-stimulating factor alone. Additionally, it predicts that infusion of white blood cells and platelets can relieve the symptoms of neutropenia and thrombocytopenia, respectively, without drastically hindering the haemopoietic recovery period after high dose chemotherapy.

Antigens, CD34↗

PubMed2002

Fludarabine/melphalan conditioning for allogeneic transplantation in patients with multiple myeloma.

The purpose of the study was to determine the feasibility and efficacy of a reduced intensity conditioning regimen of fludarabine and melphalan for allogeneic transplantation in patients with multiple myeloma. From August 1996 to December 2000, 22 patients received a reduced intensity conditioning regimen with fludarabine and melphalan. Median age was 51 years (range, 45-64), median time from initial therapy to transplant was 36 months (range, 3-135 months). Disease phase prior to transplant was primary refractory in two patients, refractory relapse in 11 patients, sensitive relapse in eight patients and initial remission consolidation in one patient. The median number of prior therapies was five (range, 1-7), and median beta 2 microglobulin prior to transplant was 3.0 mg/l (range, 1.0-7.3). All patients received unmanipulated grafts from either HLA matched sibling donors (n = 13) or matched unrelated donors (n = 9). Eighteen patients received fludarabine 30 mg/m(2) for 4 days with melphalan 140 mg/m(2) as a single dose and four patients received fludarabine 25 mg/m(2) for 5 days with melphalan 90 mg/m(2) daily for 2 days. All 21 patients evaluable for engraftment achieved a neutrophil count of >0.5 x 10(9)/l after a median of 12 days (range, 9-24), 18 patients achieved platelet transfusion independence after a median of 14 days (range, 8-47). All engrafting patients had 100% donor cell engraftment. Seven patients achieved a complete remission. Six patients are currently alive with a median follow-up of 15 months (range, 10-47 months). The actuarial survival and progression-free survival is 30 +/- 11% and 19 +/- 9% at 2 years. Non-relapse mortality at 100 days was 19 +/- 10% and 40 +/- 10% at 1 year. Fludarabine/melphalan combinations are feasible and allow consistent engraftment of allogeneic progenitor cells from both related and unrelated donors in patients with multiple myeloma and should be explored in patients with less advanced disease.

Antineoplastic Agents↗

PubMed2001

Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality.

This study investigated the use of a nonablative conditioning regimen to decrease toxicity and achieve engraftment of an allogeneic blood stem cell transplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy. Patients received a preparative regimen of fludarabine (25 mg/m(2) given daily for 5 days or 30 mg/m(2) daily for 3 days) and intravenous cyclophosphamide (1 g/m(2) given daily for 2 days or 750 mg/m(2) daily for 3 days). Nine patients received rituximab in addition to the chemotherapy. Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; their median age was 51 years. Twelve were in complete remission (CR) at transplantation. All patients achieved engraftment of donor cells. The median number of days with severe neutropenia was 6. Only 2 patients required more than one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than grade II. All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being alive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression. Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.

Adult↗

PubMed2001

Long-Term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation.

Donor lymphocyte infusions (DLIs) are an effective treatment for relapsed Chronic myeloid leukemia (CML) after allogeneic transplantation but are limited by the occurrence of GVHD. CD8+ T lymphocytes are involved in the pathogenesis of GVHD but may not be essential for the graft-versus-leukemia (GVL) effect in CML. We have treated 26 CML patients with posttransplantation relapse with CD8-depleted DLI. Thirteen of 15 patients (87%) who relapsed in early-phase CML achieved complete cytogenetic response, but only 1 of 11 who relapsed in advanced-phase disease achieved complete response. Acute GVHD occurred in 2 patients (8%), and extensive chronic GVHD occurred in 2 patients (11%). Treatment-related mortality was 11.5%. Responses were durable; with a median follow-up of 4.2 years (1-7.5 years), only 1 responding patient relapsed (7%). CD8-depleted DLI was equally effective and safe after unrelated donor transplants and sibling transplants. Cytogenetic clonal evolution at the time of DLI was not predictive of treatment failure unless associated with hematologic criteria for disease acceleration. CD8 depletion is an effective method to separate GVL from GVHD for posttransplantation relapsed CML. This strategy is associated with durable complete remissions and a low rate of complications and therefore merits further investigation in larger-scale comparative trials.

Adult↗

PubMed2001

Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: an intensive regimen for the treatment of multiple myeloma.

The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.

Adult↗

PubMed2001

Decitabine with allogeneic peripheral blood stem cell transplantation in the therapy of leukemia relapse following a prior transplant: results of a phase I study.

Relapse after allogeneic progenitor cell transplant is associated with a poor prognosis for patients with advanced leukemia, with few curative options available. Use of novel chemotherapeutic agents with limited toxicity is warranted. We investigated the role of decitabine, a pyrimidine analogue with significant anti-leukemic effect and limited toxicity, in this setting. Fourteen patients with advanced acute leukemia or transformed chronic myelogenous leukemia (CML) who had failed previous allogeneic transplant were treated. Decitabine at doses of 100 mg/m2 to 150 mg/m2 given every 12 h for 5 days was followed by infusion of stem cells from the original donor 2 to 5 days after the completion of chemotherapy. Dose of decitabine was escalated in cohorts of three patients based on the modified Fibonacci scheme. The primary study end-point was assessment of the toxicity of the regimen with secondary endpoints of response and survival. Eight patients responded with either a complete remission or partial hematological remission (absence of blasts in peripheral blood and bone marrow but with platelet count <100 x 10(9)/l). Toxicity was limited with no grade 3 or 4 toxicity directly attributable to the treatment. The median survival for all patients was 190 days (range 11 to 1215+ days). Decitabine at doses of 100 mg/m2 to 150 mg/m2 given every 12 h for 5 days, followed by stem cell infusion from the original donor was well tolerated, and was associated with acceptable myelosuppression. Current response data should encourage further study of this drug, either alone or in combination with other agents, for treatment of relapsed acute leukemia after an allogeneic transplant.

Adult↗

PubMed2000

Autologous blood cell vs marrow transplantation for acute myeloid leukemia in complete remission: an EBMT retrospective analysis.

In order to compare autologous bone marrow (BMT) and blood cell transplantation (BCT) in patients with acute myeloid leukemia (AML) in first remission (CR1), we retrospectively reviewed the data of 1393 patients registered to EBMT and undergoing either BCT (n = 100), purged (n = 252) or unpurged (n = 1041) BMT. Hematopoietic recovery was significantly quicker after BCT than after either purged or unpurged BMT. The 2-year leukemia-free survival (LFS), relapse incidence (RI) and overall survival for the entire population of patients were 52 +/- 1%, 43 +/- 1% and 58 +/- 1% and were significantly influenced by FAB subtype (M3 vs other) and the intervals between diagnosis and CR1 or CR1 and transplant. After BCT, LFS and RI were 44 +/- 6% and 50 +/- 6% and did not differ significantly from that found for unpurged BMT (49 +/- 2% and 45 +/- 2%; P = NS). However, LFS (57 +/- 3%) and RI (37 +/- 3%) of patients undergoing purged BMT were significantly different from that found for BCT patients (P = 0.01 and P = 0.006). As some characteristics of patients undergoing BCT or purged BMT differed significantly (age, intervals between diagnosis and CR1 or CR1 and transplant), the better outcome observed for purged BMT over BCT patients needs to be prospectively investigated.

Acute Disease↗

PubMed2000

High-dose ifosfamide and etoposide with filgrastim for stem cell mobilization in patients with advanced ovarian cancer.

High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation has shown promise as treatment for recurrent or persistent epithelial ovarian cancer. We evaluated the stem cell mobilization regimen of high-dose ifosfamide plus etoposide in 32 patients with epithelial ovarian cancer, who had a positive second-look laparatomy or recurrent disease. Ifosfamide was given at 10 g/m2 by continuous i.v. from days 1 to 3. Etoposide was given at 150 mg/m2 every 12 h for six doses on days 1-3. Filgrastim was given at 10 microg/kg/d s.c. from day 5 until the completion of peripheral blood stem cell harvest. Fourteen of 32 patients had measurable or evaluable disease before mobilization therapy and were assessed for response. In nine (64%) of the 14 patients, treatment response was demonstrated, and these patients received a second cycle of mobilization therapy. The target CD34+ cell dose (>8 x 106 cells/kg) was achieved with a median of one apheresis (range 1-5). A median of 25.1 (range 8.0-122.5) x 106 CD34+ cells/kg body weight was collected. Non-hematologic toxicity was limited to grade 2 renal dysfunction in one patient and grade 2 hepatic dysfunction in three patients. In this patient group, high-dose ifosfamide plus etoposide with filgrastim support was well tolerated, lead to successful stem cell harvest and had antitumor activity.

Adult↗

PubMed2000

High-dose melphalan and allogeneic peripheral blood stem cell transplantation for treatment of early relapse after allogeneic transplant.

Patients with acute leukemias relapsing within 1 year of an allogeneic BMT have a poor prognosis. We studied the use of melphalan 180 mg/m2 followed by allogeneic peripheral blood stem cells (PBSC) as salvage treatment for patients relapsing after related (n = 7) or matched unrelated transplants (n = 3). Diagnoses were AML (n = 4), ALL (n = 3), biphenotypic acute leukemia (n = 2) and CML in blast crisis (n = 1). Eight patients were beyond first relapse and none were in remission. The median time from previous transplant to relapse was 146 days (range 66-206). The melphalan dose was 90 mg/m2 intravenously on days -4 and -3 with PBSC infusion on day 0. GVHD prophylaxis consisted of cyclosporine and methylprednisolone. The median time to an absolute neutrophil count >0.5 x 10(9)/l and to a platelet count >20 x 10(9)/l was 11 and 13 days, respectively. All engrafting patients (n = 8) had 100% donor cells. Two patients died before day 30, but no other grade 3 or 4 toxicity occurred. Acute GVHD grades II-III occurred in two subjects, and chronic GVHD in four. Seven patients achieved CR, but relapsed at a median of 116 days (range 56-614). Leukemia was the cause of death in eight patients. Median survival was 149 days (range 6-614). This treatment produced responses in the majority of this poor prognosis group. However, durable remissions were not observed, and new treatments to consolidate the responses achieved in this setting are needed. This regimen could be considered for short-term disease control to facilitate donor lymphocyte infusion-based immunotherapy or other measures to prevent disease recurrence.

Acute Disease↗

PubMed2000

Early detection of relapse by hypermetaphase fluorescence in situ hybridization after allogeneic bone marrow transplantation for chronic myeloid leukemia.

PURPOSE: Standard G-band cytogenetic analysis (CG) provides information on approximately 25 metaphases for monitoring the presence of Philadelphia chromosome positive (Ph+) cells in chronic myelogenous leukemia (CML) patients, making the detection of a low frequency of Ph+ cells problematic. The purpose of this study was to improve the detection of a low frequency of Ph+ cells. PATIENTS AND METHODS: We combined fluorescence in situ hybridization (FISH) with long-term colcemid exposure, capturing several hundred metaphases in bone marrow cultures (hypermetaphase FISH [HMF]). Using probes that identify Ph+ cells, HMF was compared with CG analysis in the follow-up evaluations of 51 patients with CML at various time points after allogeneic bone marrow transplant (BMT). RESULTS: Thirty-five patients never showed the presence of Ph+ cells by either method. In four patients, high frequencies of Ph+ cells were detected by both methods. In the remaining 12 patients, Ph+ cells were detected by HMF at time points after BMT when they were not detected by CG. In seven of the 12 patients, low but statistically significant frequencies of Ph+ cells (0.37% to 5.20%) were detected 3 months or later after BMT, and when no intervention was initiated, all seven patients later relapsed. Based on those data, an eighth patient with mixed chimerism and a similar HMF-detected Ph+ frequency (1.8% at 27 months after BMT) was reinfused with donor lymphocytes and achieved remission with 0% Ph+ cells studied by HMF (up to 50 months after BMT). Ph+ cells detected by HMF but not by CG less than 3 months after BMT disappeared on later examination in two of four patients. After detection of Ph+ cells by HMF only, the median time to cytogenetic progression (detection of Ph+ cells by CG) was 101 days. CONCLUSION: The results demonstrate the ability of HMF to detect low but clinically relevant levels of leukemic cells not detected by CG in transplant patients. The data indicate that HMF can detect low levels of Ph+ cells before standard cytogenetics at a time that may be useful in monitoring disease status and planning clinical interventions.

Bone Marrow Transplantation↗

PubMed1999

Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versus-malignancy.

BACKGROUND: The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus-lymphoma effect in such patients post allogeneic hematopoietic transplantation. PATIENTS AND METHODS: Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine. RESULTS: Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7%) achieved complete and two (14.3%) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) for bcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non-responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55% (95% confidence interval (95% CI): 28%-83%). For patients with chemosensitive disease, FFP and OS at one year were both 90% (95% CI: 71%-100%) compared with 44% (95% CI: 1%-88%) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case). CONCLUSIONS: This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.

Adult↗

PubMed1999

Intensive dose ifosfamide and etoposide with G-CSF for stem cell mobilization in patients with non-Hodgkin's lymphoma.

We studied 36 patients with non-Hodgkin's lymphoma to evaluate the stem cell yield following recovery from intensive dose ifosfamide and etoposide given as mobilization chemotherapy. We also assessed the toxicity of the regimen and engraftment kinetics. All patients had intermediate grade lymphoma and had either failed to achieve a complete remission to induction chemotherapy or had relapsed. Patients received ifosfamide 10 g/m2 IV total dose given over 72 hours, etoposide 150 mg/m2 IV every 12 hours for 6 doses and G-CSF 10 microg/kg/d. Thirty-four patients went on to receive high-dose chemotherapy with BEAM or with CVP and BEAM. A median of 2 (1-10) apheresis was required to reach the target CD34+ count of >4 x 10(6)/kg. A median of 13.1 CD34+ cells/kg (4.1-148) was obtained. Toxicity was limited to mucositis in 3 patients, transient confusion and transient rise in liver function tests in 3 and 2 patients respectively. The median time to engraftment was 10 days (8-17) for all the patients undergoing high-dose chemotherapy. The regimen of intensive dose ifosfamide and etoposide along with G-CSF is well tolerated and in this group of patients has lead to successful stem cell harvests and sustained engraftment.

Adult↗

PubMed1998

Allogeneic peripheral blood stem cell transplantation for active hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder of immune dysregulation. Successful allogeneic BMT is the only therapy that has produced long-term disease-free survival. However, for patients with active HLH the outcome of BMT remains poor when compared with those transplanted in remission. We describe a patient with active, recurrent HLH treated with high-dose chemotherapy and related allogeneic peripheral blood stem cell (PBSC) transplantation. Hematologic recovery was rapid and the post-transplant course was uncomplicated. The patient is alive and well 2 1/2 years after transplant. Allogeneic PBSC transplantation may deserve further evaluation as an alternative source of stem cells for transplantation in patients with active HLH.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma.

PURPOSE: Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. PATIENTS AND METHODS: Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. RESULTS: Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. CONCLUSION: The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.

Adult↗

PubMed1997

Bone marrow transplantation after failure of autologous transplant for non-Hodgkin's lymphoma.

We evaluated the response to and toxicity of allogeneic or autologous bone marrow transplantation (BMT) for patients with non-Hodgkin's lymphoma (NHL) who relapsed after autologous BMT. Since 1990, 172 patients have received autologous BMTs in NHL at the MD Anderson Cancer Center and 75 have relapsed. Twelve patients (median age, 42 years), with disease recurrence underwent either allogeneic BMT (eight patients) or a second autologous BMT (four patients). Ten patients received thiotepa, busulfan and cyclophosphamide as conditioning, one patient received cyclophosphamide and total body irradiation and one received BCNU, etoposide, Ara-c and melphalan. The median interval between the first and second transplants was 23.5 months (range 5-80 months). Three patients who underwent allogeneic BMT had refractory relapses, three had a responsive relapse and two were in complete response (CR) at the time of BMT. Five patients received peripheral blood stem cells and three patients, allogeneic bone marrow. Three patients are alive and disease-free at 25, 22 and 7 months after allogeneic BMT. Four patients died of treatment-related causes and one from disease recurrence. All four patients undergoing autologous BMT had responsive relapses. Three patients received peripheral blood stem cells and one patient bone marrow. Two patients are alive and disease-free at 12 and 30 months after autologous transplants. There were no treatment-related deaths; two patients died of disease recurrence. This retrospective study shows that in selected patients, allogeneic or autologous BMT is an effective salvage therapy for NHL which recurs after autologous BMT.

Adult↗

PubMed1997

High-dose sequential chemotherapy and autologous stem cell reinfusion in advanced pediatric solid tumors.

Between January 1993 and December 1996, 21 children with advanced solid tumors were entered in a dose-escalating study of high-dose sequential chemotherapy followed by autologous stem cell transplantation. The diagnoses included neuroblastoma (NB) for 13 patients; Ewing's sarcoma (ES) for six patients and osteosarcoma for two patients. Nine patients received therapy as consolidation for primary metastatic disease, and 12 patients had had previous relapses. Treatment consisted of CY given i.v. at a dose of 7 g/m2 on day 1, followed by G-CSF until myeloid recovery. After 3 weeks of rest, all patients were given thiotepa i.v. on days 22-24. The total dose of thiotepa was 450 mg/m2 in three patients, 600 mg/m2 in six patients, and 750 mg/m2 in 12 patients. Melphalan was given i.v. at a dose of 180 mg/m2 i.v. on day 27 followed by stem cell infusion on day 28. Major toxic reactions included stomatitis, esophagitis, diarrhea and dermatitis. Three patients died of treatment-related complications. Twelve patients have had a relapse. Six patients (five with NB and one with ES) are alive in continuous remission 5-50 months (median 36) after transplantation. The results of this study show that it is feasible to administer high-dose sequential chemotherapy to children with advanced solid tumors.

Adolescent↗

PubMed1997

Phase I trial of cyclosporine-induced autologous graft-versus-host disease in patients with multiple myeloma undergoing high-dose chemotherapy with autologous stem-cell rescue.

PURPOSE: To determine the feasibility and toxicity of inducing autologous graft-versus-host disease (GVHD) with cyclosporine in patients with multiple myeloma undergoing autologous stem-cell transplantation. PATIENTS AND METHODS: Fourteen multiple myeloma patients with a median age of 50 years (range, 41 to 63) were enrolled. The median time from diagnosis to transplant was 651 days (range, 229 to 3,353). Ten patients had primary refractory disease, two were in first remission, and two were responsive to salvage therapy. The preparative regimen consisted of thiotepa, busulfan, and cyclophosphamide. Cyclosporine was administered daily for 28 days after the stem-cell infusion, and the dose was adjusted to maintain whole-blood cyclosporine levels between 50 and 150 ng/dL in the first seven patients (low-level group) and between 150 and 300 ng/dL in the other seven patients (high-level group). RESULTS: All patients achieved neutrophil engraftment a median of 11 days after transplant. Four patients developed > or = grade 2 hepatic toxicity, six developed > or = grade 2 nephrotoxicity, and four developed reversible cardiac toxicity. Only one treatment-related death occurred. Cyclosporine was withheld in seven patients for a median of 6 days because of renal and/or liver dysfunction. One patient developed clinical skin GVHD, which responded to corticosteroid therapy. Six patients developed histologic evidence of GVHD without clinical signs of GVHD (subclinical GVHD). The incidence of clinical and subclinical GVHD was similar in both cyclosporine groups. Three of 11 patients assessable for response achieved remissions. Three patients experienced disease progression 80, 160, and 354 days after transplant. Ten patients are alive without progression between 56 and 444 days after transplant. CONCLUSION: Induction of autologous GVHD by posttransplant cyclosporine is feasible and well tolerated in patients with multiple myeloma.

Adult↗