Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: A phase 2 study from GELTAMO.

Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory (RR) disease have poor outcomes with current salvage regimens. We conducted a phase 2 trial to analyse the safety and efficacy of adding lenalidomide to R-ESHAP (LR-ESHAP) in patients with RR DLBCL. Subjects received 3 cycles of lenalidomide 10 mg/day on days 1-14 of every 21-day cycle, in combination with R-ESHAP at standard doses. Responding patients underwent autologous stem-cell transplantation (ASCT). The primary endpoint was the overall response rate (ORR) after 3 cycles. Centralized cell-of-origin (COO) classification was performed. Forty-six patients were included. The ORR after LR-ESHAP was 67% (35% of patients achieved complete remission). Patients with primary refractory disease (n = 26) had significantly worse ORR than patients with non-refractory disease (54% vs. 85%, p = 0.031). No differences in response rates according to the COO were observed. Twenty-eight patients (61%) underwent ASCT. At a median follow-up of 41 months, the estimated 3-year PFS and OS were 42% and 48%, respectively. The most common grade ≥3 adverse events were thrombocytopenia (70% of patients), neutropenia (67%) and anaemia (35%). There were no treatment-related deaths during LR-ESHAP cycles. In conclusion, LR-ESHAP is a feasible salvage regimen with promising efficacy results for patients with RR DLBCL.

Caspofungin for the treatment of invasive fungal disease in hematological patients (ProCAS Study).

Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). This multicenter, prospective, non-comparative, observational ProCAS study was aimed to assess the effectiveness and safety of caspofungin in adult hematological patients with IC or IA under everyday clinical conditions. Favorable outcomes included complete and partial responses on the last day of caspofungin therapy. Safety was assessed up to 14 days post-caspofungin. A total of 115 patients (69 male) with a median age of 52 years (range, 23-78 years) were analyzed. Underlying disease was acute myeloid leukemia in 45 patients (39%), and 21 (18%) were allogeneic stem cell transplant recipients. Thirty-four (29.5%) patients had a diagnosis of IA and 26 (22.6%) had IC (candidemia). The median duration of caspofungin therapy was 14 days (range, 1-100). The overall favorable response rate was 77% (20/26) for patients with IC (69% first-line) and 79% (27/34) for those with IA. Antifungal therapy with caspofungin was generally well tolerated, only two (1.7%) patients having a non-serious drug-related adverse reaction. These results suggest that caspofungin, either alone or in combination, should be considered an effective and safe option for the treatment of invasive mycoses in patients with severe hematological disorders.

Unexpected postmortem diagnosis of Acanthamoeba meningoencephalitis following allogeneic peripheral blood stem cell transplantation.

Meningoencephalitis caused by pathogenic free-living amebas is usually fatal. Only a few cases of Acanthamoeba meningoencephalitis, diagnosed at autopsy, have been reported following hematopoietic stem cell transplantation. We here report a case of Acanthamoeba meningoencephalitis following allogeneic peripheral blood stem cell transplantation with rapidly evolving neurologic symptoms that remained unexplained. Magnetic resonance imaging failed to show brain lesions and cerebrospinal fluid was negative for microbiological cultures. Definite diagnosis was an unexpected autopsy finding. As overall and teaching hospital autopsy rates are declining worldwide, we must emphasize the need of autopsy exams if we want to improve our knowledge as the best way to care for our patients.

[Individualized evaluation of the risk of infections in the oncohematologic patient]. / Evaluación individualizada del riesgo de infecciones en el paciente oncohematológico.

In order to take the best approach to infection in the oncohematologic patient with fever, it is important to know not only how profound the neutropenia is and how long the patient has had it, but also the characteristics of the underlying disease, the immunosuppressive therapy received and the type of hematopoietic stem/progenitor cell transplantation performed. Moreover, is important to consider if these patients have any personal or familial history of infectious diseases. All these aspects let us calculate the net state of immunosuppression and the risk of infection, and provide us with information about the most probable etiology in each case and the best prophylaxis and treatment. In this study we review the more important advances in chemotherapy in recent years that will make it necessary in the future to change our prophylactic guidelines for more effective prevention of infection in the oncohematologic patient.

Busulfan plus cyclophosphamide followed by autologous blood stem-cell transplantation for patients with acute myeloblastic leukemia in first complete remission: a report from a single institution.

PURPOSE: To determine if peripheral-blood stem cells (PBSC) collected during the recovery of standard induction and consolidation chemotherapy in acute myeloblastic leukemia (AML) can be used as a safe tool for autologous transplantation, and to study aspects of the autologous blood stem-cell transplantation (ABSCT) procedure and their results in AML patients in first remission. PATIENTS AND METHODS: Twenty-four AML patients in first remission received busulfan (BU; 16 mg/kg) and cyclophosphamide (CY; 200 mg/kg) followed by ABSCT. PBSC were collected by continuous-flow leukaphereses after induction and consolidation courses. RESULTS: The median numbers of mononuclear cells (MNCs) and colony-forming unit granulocyte-macrophage (CFU-GM) administered were 6 x 10(8)/kg and 11 x 10(4)/kg, respectively. ABSCT induced engraftment in 22 patients and there were two graft failures. The median times to reach a polymorphonuclear (PMN) leukocyte count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L were 13 and 19 days, respectively. Fatal hepatic veno-occlusive disease (VOD) was observed in two cases. Other toxicities were mild and uncommon. Twelve patients relapsed between 1 and 9 months posttreatment. Actuarial disease-free survival (DFS) and actuarial risk of relapse at 30 months were 35% (95% confidence interval [CI], 25% to 45%) and 60% (95% CI, 50% to 72%), respectively. CONCLUSION: These preliminary results show the fast hematopoietic recovery and the low infectious and hemorrhagic morbidity associated with the procedure and strongly suggest that ABSCT may be as effective as autologous bone marrow transplantation (ABMT) in AML. However, further strategies for reducing leukemic relapse must still be investigated.

A phase II clinical trial of carboplatin infusion in high-risk acute nonlymphoblastic leukemia.

Carboplatin (CBDCA) is a second-generation platinum drug that has been shown to be useful when used as a continuous infusion in treatment of refractory adult leukemia. We report on the effectiveness of continuous infusion CBDCA, 300 mg/m2/d x 5 days, as evaluated in nine patients with secondary acute nonlymphocytic leukemia (ANLL) (seven previous myelodysplastic syndrome and two treatment-associated ANLL), three ANLL patients in first relapse, six refractory ANLL, and nine patients with blastic phase of chronic myelogenous leukemia (BP-CML). All patients were considered assessable. The response rate was 44% (eight complete remissions [CRs], four partial remissions [PRs]). Median duration of postchemotherapy neutropenia was 36 days (range, 18 to 45). Therapy was well tolerated, and toxicity was mainly hematologic and nondose-limiting. Despite prolonged neutropenia, severe infections were rarely seen, and most patients were managed as outpatients. Twelve patients had nausea and vomiting, two had symptomatic hypomagnesemia, and one patient showed reversible ototoxicity. Because of substantial antileukemic activity and unusual extrahematologic toxicity, CBDCA appears to be an effective second-line agent in the treatment of ANLL and should be considered for upgrading to first-line treatment regimens.

Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group.

PURPOSE: To analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin's disease (HD) undergoing autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Detailed records from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most patients received high-dose chemotherapy without radiation for conditioning (n = 443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250). RESULTS: The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI, 48.4% to 60.6%), respectively. In multivariate analysis, the presence of active disease at transplantation, transplantation before 1992, and two or more lines of therapy before transplantation were adverse prognostic factors for outcome. Sixteen patients developed a secondary malignancy (5-year cumulative incidence of 4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the use of total-body irradiation (TBI) in the conditioning regimen, and age > or = 40 years were found to be predictive factors for the development of second cancers after ASCT. CONCLUSION: ASCT achieves long-term disease-free survival in HD patients. Disease status before ASCT is the most important prognostic factor for final outcome; thus, transplantation should be considered in early stages of the disease. TBI must be avoided in the conditioning regimen because of a significantly higher rate of late complications, including secondary malignancies.

Transplantation of CD34+ selected peripheral blood to HLA-identical sibling patients with aplastic anaemia: results from a single institution.

We evaluated the use of CD34+ selected allogeneic peripheral blood as a source of hematopoietic progenitors for allogeneic transplantation in 11 patients with aplastic anemia (AA). The median age was 17 years (range, 6--9), and the median time between diagnosis and transplant 1 month (range, 1--4). Conditioning consisted of cyclophosphamide (50 mg/kg per day) on days--7 to--4 and antithymocyte globulin (30 mg/kg per day) on days--4 to--2 in nine patients. Total lymphoid irradiation was added to the preparative regimen for two. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and prednisone. Median doses of CD34+ and CD3+ cells infused were 3.91 x 10(6) and 0.3 x 10(6)/kg, respectively. The median time taken to achieve a neutrophil count >0.5 x 10(9)/l was 12 days and to recover a platelet count >20 x 10(9)/l, 13 days. Two patients developed acute GVHD grade I--II and one developed limited chronic GVHD. There were two treatment-related deaths. At a median follow-up of 44 months (range, 4--3), nine patients were alive with sustained and complete engraftment. This is a promising procedure in patients with AA, resulting in a rapid hematopoietic recovery, a low transplant-related mortality, and a low incidence of GVHD.

Carboplatin plus cytarabine in the treatment of high-risk acute myeloblastic leukemia.

Thirty-one patients (20 male and 11 female; median age 51 years (16-79)) with high-risk acute myeloblastic leukemia (AML) (20 refractory AML and 11 secondary AML (s-AML) (four to myelodysplastic syndrome, five to chemo/radiotherapy, one to aplastic anemia and one blastic chronic myelogenous leukemia (B-CML)) were treated with CBDCA (300 mg/m2/day x 5 days in continuous i.v. infusion) plus intermediate-dose Ara-C (500 mg/m2/day x 3 days in rapid i.v. infusion). Nine patients (29%) achieved CR (five s-AML (three myelodysplastic syndromes, one CML and one ALL) and four refractory AML) and 11 patients had resistant disease. There were 11 early deaths (35%). Median disease-free survival of the nine responders was 4 months. The main toxicity was hematological, febrile episodes took place in nearly all the patients (96%). The CBDCA plus Ara-C regimen showed an evident antileukemic activity in high-risk leukemia. However, the lack of long-term disease-free survivors shows the need for innovative postremission strategies. The high initial response rate seen in AML secondary to myelodysplastic syndromes (MDS) warrants further investigation of CBDCA in combination regimens for MDS patients.

Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis.

Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment.

Factors influencing the collection of peripheral blood stem cells in patients with acute myeloblastic leukemia and non-myeloid malignancies.

Factors influencing the collection of autologous peripheral blood stem cells (PBSCs) were studied in 182 mobilization procedures performed on 145 consecutive patients with acute myeloblastic leukemia (AML; n=67) and with various non-myeloid malignancies (NMM; n=78). PBSC were collected following mobilization with chemotherapy, treatment with granulocyte colony-stimulating factor (G-CSF) or chemotherapy plus G-CSF. Fewer colony-forming unit granulocyte-macrophages (CFU-GMs) were collected from patients with AML than from patients with NMM (P<0.0001), although there were no differences in the numbers of CD34+ cells collected between both groups. Multiple regression analysis showed that chemotherapy alone was predictive of a low CD34+ yield in patients with NMM (regression coefficient (RC)=-2.1; P=0.003). In addition, the interactions "diagnosis mutliple myeloma (MM)xmobilization with chemotherapy" (RC=2.9; P=0.004) and "diagnosis MMxmobilization with chemotherapy plus G-CSF" (RC=2.1; P=0.04) also remained in the model, both showing a favorable influence. In AML, mobilization with chemotherapy plus G-CSF was associated with higher CD34+ yields (P=0.003). In this subgroup of patients, multiple regression analysis identified the number of cycles of previous chemotherapy (< or =2 cycles; RC=1.3; P=0.03) and peripheral blood counts (WBC > or =1.5 x 10(9)/l and monocytes >20%; RC=0.8; P=0.02) as the factors most predictive of CD34+ cell yield. These findings emphasize the need to optimize harvesting technique to enhance safety and minimize morbidity and costs of this valuable procedure.

Liver disease as primary manifestation of multiple myeloma in a young man.

We report a 27-year-old man who presented with fatigue, moderate weight loss and progressive abdominal distension as primary manifestations of a light-chain multiple myeloma (MM). Liver scan showed an enlarged liver with multiple low attenuation areas. Liver biopsy revealed sinusoidal infiltration by small size cells identified as Kappa light chain-producing primitive plasma cells by immunohistochemistry. The patient responded to three courses of EDAP. Subsequently he received intensive therapy with busulfan/melfalan and a peripheral blood stem cell transplantation enriched for CD34+ cells from his HLA-identical brother. No acute graft-versus-host disease was detected. Now, 12 months after transplant, the patient is asymptomatic.

Recent improvements in outcome for elderly patients with de novo acute myeloblastic leukemia.

A retrospective analysis was performed on 263 consecutive patients aged over 60 with de novo acute myeloid leukemia (AML) diagnosed in a single institution between 1979 and 1998. Eighty-nine patients (33%) received only palliative treatment, while 174 patients (67%) were treated with different intensive chemotherapy regimens. The 5- and 10-year overall survival (OS) for the whole series was 7.7+/-1.2 and 4.3+/-1.6%, respectively. For patients receiving chemotherapy, OS was 10.5+/-2.5 and 7+/-2.6%, while for those patients receiving supportive treatment it was 1.1+/-1.1 and 0%, respectively (P=0.002). Within the group of patients receiving chemotherapy, the complete remission (CR) rate was 46%; treatment failure rate was 54% (36% due to treatment-related mortality and 18% due to resistant disease). Variables influencing CR rate were FAB subtype, CD7 positivity, chemotherapy regimen, creatinine level, hepatomegaly, and period of diagnosis. Median disease-free survival (DFS) duration was 8.4 months with a probability of being disease-free at 10 years of 10+/-5%. There were no significant differences in DFS according to age. According to the period of diagnosis (1979-1986 vs. 1987-1998), improvements in the CR rate (27 vs. 56%, P=0.0002), and OS (10.9 vs. 15.7 months, P=0.0007) were observed. This large single-center study of unselected de novo AML elderly patients substantiates the progressive improvement achieved in the management of elderly patients with AML, probably due to an improvement in supportive care and the administration of conventional induction chemotherapy.

Long-term acyclovir prophylaxis for prevention of varicella zoster virus infection after autologous blood stem cell transplantation in patients with acute leukemia.

Twenty-one adult patients with acute leukemia who underwent autologous blood stem cell transplantation (ABSCT) and who received acyclovir during the first 6 months after transplant to prevent varicella zoster virus (VZV) infection were studied retrospectively to determine the incidence and outcome of VZV infection after ABSCT. The cumulative risk of VZV infection was 32% by 1 year after transplant. No patient developed VZV while on prophylactic acyclovir but five (24%) had localized herpes zoster within 1 month of acyclovir withdrawal. There were no deaths related to VZV infection and only one patient had disseminated disease and post-herpetic neuralgia. These preliminary results suggest that the incidence and outcome of VZV infection after ABSCT largely parallel those reported in marrow transplant patients and that long-term acyclovir prophylaxis delays but does not prevent VZV infection. Prophylaxis of VZV infection after ABSCT requires new therapeutic approaches.

Transplant-related mortality in patients older than 60 years undergoing autologous hematopoietic stem cell transplantation.

Although high-dose therapy with autologous hematopoietic stem cell transplantation (ASCT) is a widely used method of dose intensification in patients with hematological malignancies, patients aged over 60 are generally excluded. We evaluated high-dose therapy and ASCT in 29 cases involving 27 such patients (median age 63 years; range 61-68) with different malignancies. Patients were eligible if they had a good performance status, normal cardiac, respiratory, and hepatic function and a serum creatinine concentration of less than 2 mg/dl (<5 mg/dl in myeloma patients). Engraftment was assessable in 27 procedures. The median time to attain 0.5 and 1 x 10(9) PMN/l was 13 days (range 9-30) and 14 days (range 10-66), respectively. The median time taken to reach a platelet count greater than 50 x 10(9)/l was 14 days (range 8-223). Five patients (17%) died in the first 100 days after transplant, in two cases due to disease progression. The remaining three patients died as a consequence of transplant-related complications, with an overall transplant-related mortality of 10%. Five patients relapsed and died between 5 and 36 months after transplant. The remaining 17 patients are still alive without disease progression, with an actuarial overall survival of 47% at 42 months (95% CI 33-61). We consider that high-dose therapy with ASCT should be considered in those elderly patients with good performance status and without general organ impairment.

Factors influencing hematopoietic recovery after autologous blood stem cell transplantation in patients with acute myeloblastic leukemia and with non-myeloid malignancies.

Factors influencing hematopoietic recovery (HR) after autologous blood stem cell transplantation (ABSCT) were analyzed in 73 patients with various non-myeloid malignancies (NMM), and in 58 patients with acute myeloblastic leukemia (AML). Peripheral blood stem cells were collected following mobilization with chemotherapy, granulocyte colony-stimulating factor (G-CSF), or chemotherapy plus G-CSF. The conditioning regimen used consisted of either chemotherapy alone (112 cases) or chemotherapy plus total body irradiation (19 cases). The median number of colony-forming units granulocyte-macrophage (CFU-GM) was similar in both groups of patients, with the median number of CD34(+) cells infused being higher in the AML group (5.4 vs 4 x 10(6)/kg; P = 0.03). Median time neutrophils >0.5 x 10(9)/l was 13 days in both groups, and median time to a platelet count >20 x 10(9)/l was longer in AML patients (14 vs 12 days; P = 0.01). In multivariate analysis, the only factors affecting neutrophil recovery in the NMM group were the CD34+ cell number (continuous model) and the CFU-GM dose (categorized model) infused, whereas for platelet recovery, previous chemotherapy also remained significant. In the AML group, the only factors significantly affecting the speed of neutrophil recovery were dose of CD34+ cells administered and the patient's age. As for platelet recovery, only the progenitor dose administered remained significant. In the NMM group, the most discriminating cut-off values for a rapid neutrophil and platelet recovery were 1.5 x 10(6) and 2.5 x 10(6) CD34+ cells/kg, respectively, and for AML patients these figures were 1.5 x 10(6) and 4 x 10(6) CD34+ cells/kg, respectively. Our results confirm the slower HR after ABSCT in AML, and highlight the importance of progenitor cell dose in accelerating HR after ABSCT.

Marked reduction in the incidence of hepatic veno-occlusive disease after allogeneic hematopoietic stem cell transplantation with CD34(+) positive selection.

Veno-occlusive disease of the liver (VOD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). To determine the incidence of, and the risk factors for the development of VOD, we performed a retrospective analysis of a series of 178 patients, who underwent allogeneic HSCT at our institution between 1990 and 1999. Busulfan and cyclophosphamide constituted the conditioning regimen most frequently administered. Bone marrow was the source of stem cells in 129 patients (73%), and peripheral blood (PBSC) in 49 patients (27%). Thirty-one patients of the PBSC group received CD34(+) positively selected grafts. Most patients were given cyclosporin A and methotrexate (MTX) as graft-versus-host disease (GVHD) prophylaxis. Overall, 30 patients (17%) developed VOD. In univariate analyses, the incidence of VOD was significantly higher in recipients of unmanipulated grafts (20% vs 0%; P = 0.01), in patients with active malignant disease at transplantation (24% vs 9%; P = 0.03), in recipients of marrow from unrelated donors (33% vs 15%; P = 0.03), in patients grafted with bone marrow (21% vs 6%; P = 0.03), and in those receiving MTX as GVHD prophylaxis (21% vs 6%; P = 0.05). Under multivariate analysis, only CD34(+) positive selection (P = 0.0004) and the status of the disease at transplant (P = 0.03) were statistically significant variables for the development of VOD. We conclude that CD34(+) positively selected PBSC transplantation could result in a marked reduction in the incidence of VOD after allogeneic HSCT.

Autologous bone marrow transplantation for patients with acute myeloblastic leukemia in relapse after autologous blood stem cell transplantation.

Leukemic relapse remains the most frequent reason for treatment failure in patients with acute myeloblastic leukemia (AML) treated with autologous blood stem cell transplantation (ABSCT). The aim of this study was to evaluate the possible role of autologous bone marrow transplant (ABMT) in patients with AML who relapse after ABSCT. Eighteen consecutive patients were enrolled in the study. At ABMT, 17 patients were in untreated relapse and one was in third complete remission (CR). The preparative regimen was BAVC, and consisted of BCNU 800 mg/m2 on day -6, M-AMSA 150 mg/m2/day on days -5 to -3, VP-16 150 mg/m2/day on days -5 to -3 and Ara-C 300 mg/m2/day on days -5 to -3. There were two regimen-related deaths (11%). Thirteen out of 17 patients in untreated relapse before ABMT achieved CR (76%). The cumulative risk of relapse was 58 +/- 13% at 3 years. Seven patients are in CR between 7+ and 53+ months, with a disease-free survival (DFS) probability of 36 +/- 12% at 3 years. The probability of DFS after ABMT was clearly higher in those patients relapsing later than 7 months after the first autograft (52%) than in patients relapsing earlier (20%)(P = 0.02). In a significant proportion of patients, remission duration was clearly longer after ABMT than ABSCT. We conclude that BAVC conditioning followed by ABMT is associated with a low treatment-related toxicity and results in prolonged DFS in a substantial number of AML patients who relapse after ABSCT. Until better therapeutic options become available, ABMT in untreated relapse is a useful alternative in this group of very poor-risk patients.

Unrelated donor cord blood transplantation in adults with chronic myelogenous leukemia: results in nine patients from a single institution.

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults is not well established. We report the results of UD-CBT in nine adult patients with chronic myeloid leukemia (CML). The median age was 27 years (range, 19-41 years), and the median weight was 62 kg (range, 45-78 kg). At transplant, six patients were in chronic phase (five in first, and one in second), two in blast crisis, and one in accelerated phase. Eight had received intensive chemotherapy, and three had undergone autologous peripheral blood hematopoietic stem cell transplantation. Four had received interferon with no cytogenetic response, and only three underwent UD-CBT within 1 year of diagnosis. After serological typing for class I antigens, and high-resolution DNA typing for DRB1, the degree of HLA match between patients and cord blood (CB) units was 4/6 in six cases and 5/6 in three cases. The median number of nucleated cells infused was 1.7 x 10(7)/kg (range, 1.2 to 4.9 x 10(7)/kg), and was above 2 x 10(7)/kg in only two cases. All patients received thiotepa, busulfan, cyclophosphamide and anti-thymocyte globulin as conditioning; cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis; and G-CSF from day +7 until engraftment. All seven evaluable cases engrafted. The median time to reach an absolute neutrophil count > or =0.5 x 10(9)/l and > or =1 x 10(9)/l was 22 days (range, 19-52 days) and 28 days (range, 23-64 days), respectively. In the four patients evaluable for platelet recovery time to levels of > or =20 x 10(9) platelets/l, > or =50 x 10(9) platelets/l, and > or =100 x 10(9) platelets/l, these ranged from 50 to 128 days, 60 to 139 days, and 105 to 167 days, respectively. Three patients developed acute GVHD above grade II, and three of the five patients at risk developed extensive chronic GVHD. Four patients, all transplanted in chronic phase, remain alive in molecular remission more than 18, 19, 24 and 42 months after transplantation. These preliminary results suggest that UD-CBT may be considered a reasonable alternative in adults with CML who lack an appropriate bone marrow donor.

Early infections in adult patients undergoing unrelated donor cord blood transplantation.

Early transplant-related mortality after cord blood transplantation from unrelated donors (UD-CBT) is close to 50%, mainly due to infectious complications. We have studied the incidence and characteristics of early infections (before day 100) in a series of 27 adult patients (median age 30 years, range 16-46) undergoing UD-CBT at a single institution. All 27 patients experienced at least one infectious episode and 18 (66%) suffered a severe infection. Bacteremia occurred in 55% of patients (13 with Gram-positive and 11 with Gram-negative microorganisms). Eleven of 19 CMV-seropositive patients (58%) developed CMV antigenemia and one patient had CMV disease. Fungal infections were documented in three patients (11%), comprising invasive fungal infections in two cases and a localized esophagitis in one. Ten patients (37%) died before day 100 after transplantation. Infection was considered the primary cause of death in four patients (sepsis by Acinetobacter spp. bacteremia in three cases) and contributed to death in another four. The most striking findings in this series were the high incidence of, and mortality due to multiresistant Acinetobacter spp. and the low incidence of and lack of mortality due to CMV disease. This report confirms that infection is a major complication in adults undergoing UD-CBT.