Cytomegalovirus infection causes delayed platelet recovery after bone marrow transplantation.

The pathogenic effect of cytomegalovirus (CMV) infection on the hematopoietic recovery after bone marrow transplantation (BMT) was retrospectively studied in 87 recipients of (nonpurged) autologous BMT and in 56 recipients of allogeneic BMT from HLA-identical siblings. Indications for autologous BMT were lymphomas or acute leukemias and for allogeneic BMT various malignancies or aplastic anemia. Patients were divided for the study in two groups, CMV-positive and CMV-negative on the basis of the CMV status pretransplant, and CMV-negative patients were kept CMV-negative by the local transfusion policy. In allogeneic BMT recipients, platelet recovery was significantly slower in CMV-positive patients than in CMV-negative patients (platelets greater than 50,000 cells/microL after 41 days v 27 days, P = .007). This difference held true when patients with acute graft-versus-host disease above grade I were excluded (platelets greater than 50,000 cells/microL after 42 days v 24 days, P = .01). In autologous BMT, the negative effect on platelet recovery was present in patients with lymphomas, but absent in patients with acute leukemias. Patients with acute leukemias had a very delayed recovery of platelets and granulocytes after autologous BMT, irrespective of the CMV status, probably due to the original stem cell disorder. Platelet recovery was significantly slower in CMV-positive autologous BMT recipients with lymphomas than in those not infected (platelets greater than 50,000 cells/microL after 36 days v 24 days, P = .0002). The presence of CMV infection had no effect on the recovery of granulocytes in autologous or allogeneic BMT. These data show that CMV infection causes delayed platelet recovery after BMT; however, in autologous BMT, the underlying disease (ie, acute leukemia) is more determinant for hematopoiesis after BMT.     

Successful second allogeneic bone marrow transplantation in a relapsed acute myeloid leukemia patient with fungal liver abscess

Summary Disseminated fungal infection not infrequently complicates the course of allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised patients, and the prognosis of BMT patients who develop systemic fungal infection is very poor. We describe a patient who developed disseminatedCandida albicans infection with liver abscess after the first allo BMT for acute myelogenous leukemia (FAB M2). The infection was successfully eradicated by the administration of miconazole and amphotericin B. However, 1 year after the first allo BMT, the patient suffered a relapse of acute myelogenous leukemia with fungal liver abscess. A second allo BMT, accelerating granulocyte recovery by recombinant human granulocyte colony-stimulating factor (rhG-CSF), was successfully performed and the fungal liver abscess resolved with a combination therapy of fluconazole and amphotericin B. The patient is alive and free of both leukemia and fungal disease more than 37 months after the first allo BMT and 25 months after the second allo BMT.     

Flow cytometric reticulocyte quantification in the evaluation of hematologic recover

Abstract: The role of flow cytometric reticulocyte (RET) counting and the immature RET fractions (IRF) in the evaluation of hematopoietic recovery following chemoradiotherapy-induced aplasia was studied. RET counts and IRF were studied using an automated flow cytometric reticulocyte counter (Sysmex R-2000) in three groups of patients: 58 patients undergoing an autologous bone marrow transplantation (ABMT group), 28 of whom received granulocyte colony-stimulating factor (G-CSF); 28 patients undergoing an allogeneic bone marrow transplantation (BMT group); and 28 patients receiving remission-induction chemotherapy for acute leukemia (CHEMO group). To evaluate the IRF the percentages of RET fractions with middle and high fluorescence reticulocyte (MFR and HFR, respectively) were used. A rising IRF (expressed as the percentage of MFR ± HFR) was the first sign of hematopoietic recovery (ABMT group, IRF 9 days versus 18 days for the absolute neutrophil count (ANC); BMT group, 15 versus 18 days; CHEMO group, 9 versus 11 days). When recovery of the ANC (>0.5 times 109/1) was compared with that of the IRF (MFR ± HFR > 5%), statistically significant differences were found in all three groups. Additionally, 93.1% of the ABMT, 92% of the BMT and 91.2% of the CHEMO recovered the IRF before the ANC. In conclusion, an elevation in the percentage of IRF is the first sign of hematologic recovery in the majority of patients receiving remission-induction chemotherapy and the first sign of engraftment in those submitted to ABMT or BMT. Serial automated flow cytometric quantitative reticulocyte counting provides a useful and early measure of erythropoiesis indicative of hematopoietic reconstitution or successful bone marrow engraftment following marrow transplantation.     

Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: A phase-II study (no. 06901) of the EORTC Leukemia Cooperative Group

 Twenty-one patients with acute myeloid leukemia (AML) who failed to enter complete remission (CR) after first-line standard-dose remission-induction therapy with 7 days of cytarabine and 3 days of daunorubicin were treated with a salvage regimen containing intermediate-dose cytosine arabinoside (Ara-C) 2×500 mg/m²/day during 7 days in combination with continuous infusions of idarubicin 12 mg/m²/day on days 1, 3, and 5. Twenty patients were considered primary resistant, and one patient had a partial remission after two remission-induction courses. Overall, 11 patients (52%, 95% confidence interval: 30–74%) entered CR. Three patients died during hypoplasia and seven patients had resistant disease or a partial remission. The remission rate in this study compares favorably with the results obtained in similar patient categories. The toxicity of this salvage regimen was remarkably mild. No extramedullary toxicity was observed except for hepatic dysfunction in seven patients. The median duration of remission was 8.5 months, and ultimately, all complete remitters have relapsed except the patient who died from infectious complications after allogeneic bone marrow transplantation (BMT). This study shows that new intensive chemotherapy regimens may be effective after failure of primary treatment. Salvage regimens containing intermediate/high-dose Ara-C and/or alternative anthracyclines or anthracenes should be induced in the treatment of young patients with de novo AML. Received: 12 September 1995 / Accepted: 24 November 1995     

Second bone marrow transplantation after leukemia relapse in 11 patients

Since June 1977 eight patients with acute leukemia and three with chronic myelogenous leukemia (CML) have undergone cytoreductive therapy prior to a second allogeneic or syngeneic bone marrow transplantation (BMT). The median age was 24 years (range 7-49 years) and the median time to second BMT was 495 days (range 122-1887 days). Prompt hematopoietic recovery was documented in 11/11 patients and verified by cytogenetic analysis in 7/11. Early death (less than 100 days) was the result of sepsis in one, veno-occlusive disease in one and interstitial pneumonitis in two. Of seven patients who survived beyond 1 year, two patients subsequently died, one as a result of acute respiratory failure and one of leukemia relapse. Five are currently disease-free at 8+, 20+, 42+, 49+ and 72+ months after the second BMT. In this patient population which is at high risk for resistant disease and treatment-related toxicity, a second preparative therapy and BMT may offer a durable disease remission with tolerable toxicity.     

Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children's Cancer Study Group

Despite improvements in the treatment of acute myeloid leukemia (AML), approximately 50% of children die of the disease. Clinical trials in adult patients with AML indicate that idarubicin may have superior efficacy when compared to daunorubicin in the remission-induction phases of chemotherapy. We conducted consecutive clinical trials in children with newly diagnosed AML in which daunorubicin (group 1, n = 102) or idarubicin (group 2, n = 160) was used during the remission-induction (RI) and the early consolidation phases of chemotherapy. Idarubicin was given at a dose of either 10 mg/m(2) (group 2A, n = 106) or 12 mg/m(2) (group 2B, n = 53). A high rate of RI was achieved for all groups (95% group 1, 90% group 2A, 94% group 2B). There were no significant differences in 5-year event-free survival (EFS) or in overall survival (OS) when the 3 groups were compared (group 1: EFS 50%, OS 56%; group 2A: EFS 50%, OS 60%; group 2B: EFS 34%, OS 50%). RI deaths resulting from treatment toxicity were low-2% for group 1 and 5% for group 2. More gastrointestinal, pulmonary, and renal toxicity but fewer infections were observed in patients receiving idarubicin (P <.001, P =.04, P =.03, respectively). Following RI chemotherapy, all patients received 3 to 4 more courses of identical chemotherapy and then underwent either autologous (n = 156) or an allogeneic bone marrow transplantation (BMT) (n = 35). OS was higher in allogeneic BMT patients than in autologous BMT patients (79% vs 63%; P =.23). We conclude that daunorubicin is as effective as idarubicin for remission-induction therapy for childhood AML and has reduced toxicity.     

Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance?

Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT.     

Allogeneic or autologous bone marrow transplantation for acute lymphoblastic leukemia in first complete remission

Forty-seven patients with high risk acute lymphoblastic leukemia (ALL) received an allogeneic (allo) or autologous (auto) bone marrow transplant (BMT). Patients in both groups were comparable in terms of age, initial presentation of ALL and induction chemotherapy. Allo patients were transplanted earlier (median 3 months after CR) than auto patients (median 6.5 months after CR). Auto patients received more consolidation chemotherapy before BMT. All patients received total body irradiation 2.2 Gy/day x 5 days after cyclophosphamide 60 mg/kg x 2 (18 allo and five auto) or melphalan 140 mg/m2 (seven allo and 17 auto). Prevention of graft-versus-host disease (GVHD) was by conventional immunosuppression in 17 patients and T cell depletion in eight. Seven patients (28%) developed moderate to severe acute GVHD. Auto marrow was treated in vitro in each case. Seven patients died in CR from BMT complications (five allo and two auto). The probability of relapse was 9% for patients receiving allo BMT and 52% for patients receiving auto BMT (p less than 0.01). The disease-free survival was 71% for allo BMT and 40% for auto BMT (p = NS). Early BMT is an effective form of consolidation for high risk patients with ALL in first CR. An allogeneic anti-leukemia effect was demonstrated in this study.     

Delay in platelet recovery after bone marrow transplantation: impact of cytomegalovirus infection

The effect of cytomegalovirus (CMV) infection on hematopoietic recovery after marrow-ablative chemoradiotherapy followed by autologous bone marrow transplantation (BMT) was studied in patients with non-Hodgkin's lymphoma of high-grade malignancy and in patients with acute leukemia. The recovery of platelets after autologous BMT occurred significantly quicker in CMV-negative patients than in CMV-positive patients (platelets greater than 50,000 per cubic millimeter after 21 1/2 v 40 days, respectively). No differences in the recovery of neutrophils were found between those with or without CMV infection. CMV-positive patients required significantly more transfusion support with thrombocyte concentrates than CMV-negative patients (three v six thrombocyte concentrates). In conclusion, CMV infections do not influence neutrophil recovery but do delay platelet recovery. As a consequence, patients with a CMV infection, whether primary, reactivated, or latent, require more thrombocyte concentrates, which increases the risk of transfusion-related infections.     

Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a prospective study

Donor leukocyte infusion (DLI) alone has very limited efficacy for patients with acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic bone marrow transplantation (BMT). We, therefore, prospectively tested the efficacy of cytoreductive chemotherapy (intermediate-dose cytarabine+idarubicin+etoposide) followed immediately by G-CSF-primed DLI (Chemo-DLI) in 10 relapsed ALL patients after allogeneic BMT. Seven achieved complete remission (CR) at a median of 25 days (19-73 days) after DLI. Of these seven CR patients, only one remains alive in CR 907 days after DLI. Two CR patients died in CR of graft-versus-host disease. The remaining four CR patients relapsed at a median of 153 days (120-991 days) after DLI. One is alive with leukemia at post-DLI day 1217. The median survival duration after DLI was 175 days (15-1217 days). In summary, although Chemo-DLI for relapsed ALL after allogeneic BMT induced a relatively high CR rate, durable remissions were rare. Although our data should be interpreted cautiously considering the small number of patients, these results suggest that poor outcome of DLI in relapsed ALL may be primarily due to intrinsic resistance to graft-versus-leukemia effect rather than to the rapid pace of the disease.     

Results of intensive therapy in childhood acute myeloid leukemia, incorporating high-dose melphalan and autologous bone marrow transplantation in first complete remission

Childhood acute myeloid leukemia (AML) has a poor prognosis with standard chemotherapy. Allogeneic bone marrow transplantation (BMT) in remission improves the outlook only for the one third of patients with sibling donors. Autologous BMT with a lower morbidity and mortality is available to all. In this study, maximum cytoreduction was achieved by intensive early chemotherapy. Final intensification, with autologous BMT was offered to all those remaining in first complete remission (CR). Patients received two induction and two consolidation courses of intensively scheduled chemotherapy. Cytoreduction was assessed on day 14 and remission was assessed after courses 2 and 4. Bone marrow was harvested after recovery from the second consolidation course or after the first maintenance course and separated on a discontinuous percoll gradient before cryopreservation. Twenty-eight of 31 consecutively enrolled patients achieved CR. Three relapsed early and, of the 25 eligible, 24 underwent autologous BMT. Twenty-three patients received high-dose melphalan and 1 received busulphan and cyclophosphamide before autologous BMT at a median of 113 days (range, 86 to 301) after initial CR. Trilineage engraftment occurred in all. Neutrophil recovery to greater than 0.5 x 10(9)/L occurred at a median of 46 days (range, 13 to 92) after autologous BMT. Platelet recovery was delayed, with a median time to achieve greater than 20 x 10(9)/L of 42 days (range, 18 to 215). With a minimum follow up of 25 months following autologous BMT only 3 children have relapsed. The 5-year event-free survival rate (EFS) from diagnosis is 68% (95% confidence interval, 46% to 90%). Five- year EFS following autologous BMT is 87% (95% confidence interval, 67% to 100%). Autologous BMT with high-dose melphalan administration after intensive chemotherapy has produced EFS equivalent to allogeneic BMT and is associated with a strikingly low relapse rate. High-dose melphalan appears to be a valuable agent for conditioning therapy in AML.     

Influence of recombinant human granulocyte colony-stimulating factor (filgrastim) on hematopoietic recovery and outcome following allogeneic bone marrow transplantation (BMT) from volunteer unrelated donors.

Effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF, filgrastim) on hematopoietic recovery and clinical outcome in patients undergoing allogeneic bone marrow transplantation (BMT) from volunteer unrelated donors (VUD) were analyzed retrospectively. Additionally, the influence of baseline patient and transplant characteristics on hematopoietic recovery was evaluated. From January 1994 to March 1996, 47 consecutive adult patients received VUD-BMT. GVHD prophylaxis was cyclosporin A/short course methotrexate/prednisolone, and in four patients additional ATG. Post-transplantation, cohorts of patients received rhG-CSF (5 microg/kg/day) (n = 22) or no rhG-CSF (n = 25) in a non-randomized manner. The patient groups with and without rhG-CSF were rather comparable with respect to baseline patient and transplant characteristics. Median time to neutrophil counts (ANC) >500/microl was 14 days with rhG-CSF vs 16 days without rhG-CSF (P = 0.048), to ANC >1000/microl was 15 vs 18 days (P = 0.084). Neutrophil recovery was accelerated in patients receiving more than the median MNC dose of 2.54 x 10(8)/kg with a median time to ANC >1000/microl of 13 days vs 19 days (P = 0.017). RhG-CSF did not influence platelet recovery and incidence of infectious complications. Incidence of acute GVHD II-IV was 50% with rhG-CSF and 28% without rhG-CSF (P = 0.144), but death before acute GVHD II-IV occurred in 9% of patients with and 20% of patients without rhG-CSF. The median follow-up time was 38 and 36 months in patients with and without rhG-CSF, respectively. Survival at 2 years post-transplant was 39% (95% confidence interval (18%, 60%)) in patients with rhG-CSF and 24% (95% confidence interval (7%, 41%)) in patients without rhG-CSF. Administration of rhG-CSF after VUD-BMT may lead to more rapid neutrophil recovery, but did not influence the incidence of infectious complications. Patients receiving rhG-CSF showed a slightly higher incidence of acute GVHD II-IV. Higher numbers of MNC in the marrow graft accelerated hematopoietic engraftment.     

Allogeneic bone marrow transplantation versus chemotherapy in the treatment of childhood acute lymphoblastic leukemia in second complete remission

Seventy-six patients between the ages of 2 and 17 years with acute lymphoblastic leukemia (ALL) achieved a second complete remission induced by polychemotherapy. Twenty-one had an HLA-identical donor and underwent allogeneic bone marrow transplantation (BMT) after conditioning with total body irradiation and cyclophosphamide. The remaining 55 patients lacked a suitable donor and received intensive chemotherapy as treatment. Fifteen patients were excluded from the analysis because they relapsed within 3 months after achieving a second complete remission. Three of the 21 BMT patients died of transplant-related complications and seven relapsed between 90 and 480 days after transplantation. Eleven patients are alive and disease free at 5.5-71 months with an actuarial survival of 47.1%; eight patients are on a plateau extending from 22 to 71 months. Thirty-three patients treated with chemotherapy died from relapse and seven are alive and disease free 7.5-99 months from the second remission, with an actuarial survival of 9%. The probability of survival was significantly higher in the BMT group (p less than 0.025). The probability of remaining in complete remission in the BMT group was 58.5% versus 10.9% in the chemotherapy group (p less than 0.005). Our results show that BMT is the best alternative therapy for children affected by ALL who have had a relapse in the marrow.     

Treatment results of bone marrow transplantation in Kyushu Cancer Center. Bone Marrow Transplantation Team

Twenty children with various hematological malignancies (nine with acute lymphoblastic leukemia, eight with acute non-lymphoblastic leukemia, two with chronic myelogenous leukemia, one with malignant lymphoma and one with 7-monosomy) and four with severe aplastic anemia were treated with allogeneic or syngeneic bone marrow transplantation (BMT) between September 1977 and September 1988. Eleven patients are surviving currently and ten are disease free 8 to 51 months after BMT. Conditioning regimen consisted of total body irradiation (TBI) and cyclophosphamide in twenty patients. Two patients did not receive TBI. Graft failure was observed in five patients and complete recovery of recipient marrow was seen in two of them. Eleven patients developed acute graft-versus-host disease (GvHD) with grade I-II in eight patients. Three patients suffered from chronic GvHD. Seven patients with acute leukemia relapsed and all but one died of leukemia. Early death occurred in two undergone BMT in poor clinical conditions. Performance status in 100% in surviving patients except one. Efforts to improve these results are that BMT should be considered early in the course of their disease for patients who are at risk for relapse with conventional chemotherapy and improved conditioning regimens to reduce leukemia relapse after BMT for patient with the second or subsequent remission.     

CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies

After autologous or allogeneic transplants of peripheral blood stem cells (PBSC), an adequate dose of CD34+ cells is necessary to ensure early and sustained hematopoietic engraftment and favorable clinical outcome. There are no comparable data on the relationship between CD34+ cell dose and recovery after allogeneic bone marrow transplants (BMT). Twenty-eight patients with hematologic malignancies received a BMT from an HLA-identical sibling, using T-cell depletion and cyclosporin for graft-versus-host disease prophylaxis and delayed donor lymphocyte transfusions in an attempt to prevent leukemia relapse. The treatment- related mortality (TRM), primarily due to infections and cytopenias, was significantly higher for 13 patients receiving less than 1 x 10(6) CD34+ cells/kg (64.9% +/- 12.8% v 6.9% +/- 6.4%, P = .003). Survival at a median follow-up of 1 year was also lower in the group receiving less than 1 x 10(6) CD34+ cells/kg (30.8% +/- 12.8 v 74.3% +/- 13.7%, P = .005). The CD34+ cell dose was the only variable significantly associated with TRM. The dose of CD34+ cells also correlated with speed of hematopoistic recovery. Patients receiving more than 2 x 10(6) CD34+ cells/kg showed significantly earlier recovery of monocytes and a trend for earlier recovery of lymphocytes. They achieved platelet and red blood cell transfusion independence earlier, required less granulocyte colony-stimulating factor support during ganciclovir treatment, and spent fewer days in the hospital after transplantation. These results suggest that, for allogeneic T-cell-depleted BMT, the higher CD34+ cell doses may improve outcome in engrafting patients.     

Cytomegalovirus infection after autologous bone marrow transplantation with comparison to infection after allogeneic bone marrow transplantation

Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P = .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P = .02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P less than .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v 23%, P less than .001).     

Isolated extramedullary relapse presenting as autologous lymphocyte response

Isolated EMR in the CNS is a relatively rare form of recurrent leukemia. We report here a case of a 38-year-old man with inv(16) acute myeloid leukemia (AML, M2) who suffered a central nervous system (CNS) relapse after allogeneic bone marrow transplantation (BMT) from a human leukocyte antigen (HLA)-matched sibling donor. After complete remission was achieved by chemotherapy, he received allogeneic BMT from his HLA-matched sister. His leukemia relapsed in the CNS 2.5 years after the allogeneic BMT. Lumbar puncture revealed 780/muL white blood cells with 67.3% leukemia cells and 32.7% mature lymphocytes. Fluorescent in situ hybridization (FISH) using a probe for the Y chromosome demonstrated that both leukemia cells and lymphocytes in the cerebrospinal fluid (CSF) were derived from the recipient, although the bone marrow cells were from the donor. No leukemia cells with inv(16) were detected by FISH in the bone marrow. This is the first report to clarify the chimerism of lymphocytes in the CSF of patients with isolated EMR in the CNS after allogeneic SCT, in which analysis revealed that autologous immunologic cells rather than donor lymphocytes responded to the recurrent isolated leukemic cells in CNS. This observation suggests that the CNS is a "sanctuary" site not only from chemotherapy but also from the graft-versus-leukemia effect. The present case contributes to our understanding of the possibility of immunological escape phenomenon of recurrent leukemia cells in extramedullary sites.     

Reduced-intensity stem cell transplantation using allogeneic peripheral blood stem cells from the same donor for relapsed leukemia after bone marrow transplantation

We report the clinical courses of two cases with relapsed acute lymphoblastic leukemia (ALL) after allogeneic bone marrow transplantation (BMT). After reinduction chemotherapy, the patients received reduced-intensity stem cell transplantation using allogeneic peripheral blood stem cells harvested from their previous BMT donors. The conditioning regimen used consisted of fludarabine and melphalan. Graft-versus-host disease (GVHD) prophylaxis was performed with low dose cyclosporin A (CsA, 1 mg/kg/day d.i.v.) on its own. The regimen related toxicity was minimal, and stable engraftment was achieved. Since acute GVHD had not developed by day 30, CsA was stopped abruptly in both cases. After CsA withdrawal, acute GVHD developed, and subsequent chronic GVHD. One of two cases is alive without any relapse of the leukemia 40 months after the peripheral blood stem cell transplantation (PBSCT). In the other case, ALL relapsed 15 months after the PBSCT, however, complete remission was again induced concomitantly with reactivated GVHD. In both these cases, the results suggest that using PBSC as a stem cell source and abrupt cessation of GVHD prophylaxis provided a potent graft-versus-leukemia effect.     

Allogeneic bone marrow transplantation for hematological malignancies following therapy with high doses of busulphan and cyclophosphamide

Thirty patients with malignant hematological disease underwent allogeneic bone marrow transplantation following Busulphan (Bu) and Cyclophosphamide (Cy). The diseases were chronic myelogenous leukemia, acute lymphoblastic and non lymphoblastic leukemia, myelofibrosis and multiple myeloma in complete remission and in relapse. A sustained disease-free survival (DFS) was achieved in 0/5 acute leukemia patients transplanted in relapse, in 5/7 acute leukemia patients transplanted in remission (600-1550 days) and in 6/9 CML patients transplanted in the chronic phase of the disease (500-950 days). A sustained DFS was also achieved in one 2nd BMT for relapsed CML. The data suggest that the Bu-Cy protocol combines high tumor ablative capability with toxicity comparable to previously described conditioning regimens for allogeneic BMT, particularly in diseases involving a great expansion of the bone marrow.     

Resolution of psoriasis after allogeneic bone marrow transplantation for chronic myelogenous leukemia: late complications of therapy

Treatment of autoimmune disease with bone marrow transplantation (BMT) is under investigation. A few reports of patients undergoing allogeneic BMT for malignant conditions observed the resolution of psoriasis after BMT, with minimal late morbidity. We describe a patient with chronic myelogenous leukemia (CML) whose psoriasis resolved completely after allogeneic BMT. However, the patient's course was complicated by extensive chronic graft-versus-host disease (GVHD), recurrent serious infections, poor performance status and quality of life, and severe disability. The patient died 887 days post transplant due to infectious complications. The potential benefits and risks of treatment of autoimmune diseases with allogeneic BMT are discussed.