Leukemia In Second Complete Remission Research Articles

Measurable residual disease status and outcome of transplant in acute myeloid leukemia in second complete remission: a study by the acute leukemia working party of the EBMT

Measurable residual disease (MRD) prior to hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML) in first complete morphological remission (CR1) is an independent predictor of outcome, but few studies address CR2. This analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation registry assessed HCT outcomes by declared MRD status in a cohort of 1042 adult patients with AML CR2 at HCT. Patients were transplanted 2006–2016 from human leukocyte antigen (HLA) matched siblings (n = 719) or HLA 10/10 matched unrelated donors (n = 293). Conditioning was myeloablative (n = 610) or reduced-intensity (n = 432) and 566 patients (54%) had in-vivo T cell depletion. At HCT, 749 patients (72%) were MRD negative (MRD NEG) and 293 (28%) were MRD positive (MRD POS). Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months (P < 0.001). Two-year relapse rates were 24% (95% CI, 21–28) and 40% (95% CI, 34–46) in MRD NEG and MRD POS groups (P < 0.001), respectively. Leukemia-free survival (LFS) was 57% (53–61) and 46% (40–52%), respectively (P = 0.001), but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.

Hematopoietic stem cell transplantation for adults with relapsed acute promyelocytic leukemia in second complete remission.

We retrospectively compared outcomes of a large series of adult patients with APL in CR2 receiving alloHSCT (n = 228) or autoHSCT (n = 341) reported to the European Society for Blood and Marrow Transplantation from January 2004 to December 2018. The 2-year cumulative incidence of non-relapse mortality was significantly higher for alloHSCT 17.3% (95% CI 12.5-22.8) compared with autoHSCT 2.7% (95% CI 1.2-5) (p = 0.001), while differences in relapse rate were not significant (28% versus 22.9%; p = 0.28). Leukemia-free survival (LFS) and overall survival (OS) favored autoHSCT with 74.5% (95% CI 69-79.2) and 82.4% (95% CI 77.3-86.5) compared with alloHSCT with 54.7% (95% CI 47.5-61.3) (p = 0.001) and 64.3% (95% CI 57.2-70.6), respectively (p = 0.001 and p = 0.001). Multivariable analysis showed significantly worse LFS after alloHSCT (HR 0.49; 95% CI 0.37-0.67; p < 0.0001), older age (p = 0.001), and shorter time from diagnosis to transplant (p = 0.00015). Similar results were obtained for OS. The study shows that autoHSCT resulted in better survival outcomes (LFS and OS) for APL in CR2. These results were mainly due to reduced NRM in the autoHSCT as compared to alloHSCT.

High rate of durable remissions post autologous stem cell transplantation for core-binding factor acute myeloid leukaemia in second complete remission

High rate of durable remissions post autologous stem cell transplantation for core-binding factor acute myeloid leukaemia in second complete remission

Allogeneic haemopoietic transplantation for acute myeloid leukaemia in second complete remission: a registry report by the Acute Leukaemia Working Party of the EBMT.

Allogeneic haemopoietic cell transplant (allo-HCT) may be curative in acute myeloid leukaemia (AML) in second complete remission (CR2) but the impact of reduced intensity (RIC) versus myeloablative conditioning (MAC) is uncertain. The Acute Leukaemia Working Party of the European Society for Blood and Bone Marrow Transplantation Registry studied an AML CR2 cohort characterised by age ≥ 18 years, first allo-HCT 2007-2016, available cytogenetic profile at diagnosis, donors who were matched family, volunteer unrelated with HLA antigen match 10/10 or 9/10 or haplo-identical. The 1879 eligible patients included 1010 (54%) MAC allo-HCT recipients. In patients <50 years (y), two year outcomes for MAC vs RIC allo-HCT were equivalent with leukaemia-free survival (LFS) 54% for each, overall survival (OS), 61% vs 62%, non-relapse mortality (NRM) 18% vs 15% and graft versus host disease relapse-free survival (GRFS) 38% vs 42%. In patients ≥50 y, 2 y outcomes for MAC vs RIC allo-HCT were equivalent for LFS 52% vs 49%, OS 58% vs 55% and GRFS 42.4% vs 36%. However, NRM was significantly inferior after MAC allo-HCT, 27% vs 19% (P = 0.01) despite worse cGVHD after RIC-allo (32% vs 39%). These data support the need for ongoing prospective study of conditioning intensity and GVHD mitigation in AML.

Autologous Hematopoietic Stem Cell Transplantation in Acute Myelogenous Leukemia.

The clinical outcomes of autologous hematopoietic stem cell transplantation (ASCT) in acute myelogenous leukemia (AML) have improved over time. Indeed, numerous studies have demonstrated that ASCT is associated with a lower relapse rate and acceptable nonrelapse mortality compared with chemotherapy alone in patients with AML. In addition, ASCT is also associated with comparable overall survival outcomes to those of allogeneic hematopoietic stem cell transplantation in some patients with AML. To date, age, cytogenetic and molecular risk stratification, and minimal residual disease (MRD) status have been shown to be closely related to clinical outcomes following ASCT. ASCT is recommended for patients with favorable-risk and intermediate-risk AML in first complete remission and patients with acute promyelocytic leukemia in second complete remission for whom a matched sibling donor is not available. MRD status pre-ASCT is the most important factor to consider when determining whether a patient is eligible for ASCT and can effectively predict clinical outcomes after ASCT. Advanced age is not an absolute contradiction for ASCT. In this review, we describe the literature and clinical trials evaluating the outcomes of ASCT in patients with AML and discuss the indications for ASCT therapy. Because the greatest concern in ASCT recipients is early relapse, important factors that should be monitored before ASCT and future perspectives in this area are also presented.

Hematopoietic Stem Cell Transplantation Activity in Pediatric Cancer between 2008 and 2014 in the United States: A Center for International Blood and Marrow Transplant Research Report

This Center for International Blood and Marrow Transplant Research report describes the use of hematopoietic stem cell transplantation (HSCT) in pediatric patients with cancer, 4408 undergoing allogeneic (allo) and3076 undergoing autologous (auto) HSCT in the United States between 2008 and 2014. In both settings, there was a greater proportion of boys (n = 4327; 57%), children < 10 years of age (n = 4412; 59%), whites (n = 5787; 77%), and children with a performance score ≥ 90% at HSCT (n = 6187; 83%). Leukemia was the most common indication for an allo-transplant (n = 4170; 94%), and among these, acute lymphoblastic leukemia in second complete remission (n = 829; 20%) and acute myeloid leukemia in first complete remission (n = 800; 19%) werethe most common. The most frequently used donor relation, stem cell sources, and HLA match were unrelated donor (n = 2933; 67%), bone marrow (n = 2378; 54%), and matched at 8/8 HLA antigens (n = 1098; 37%) respectively. Most allo-transplants used myeloablative conditioning (n = 4070; 92%) and calcineurin inhibitors and methotrexate (n = 2245; 51%) for acute graft-versus-host disease prophylaxis. Neuroblastoma was the most common primary neoplasm for an auto-transplant (n = 1338; 44%). Tandem auto-transplants for neuroblastoma declined after 2012 (40% in 2011, 25% in 2012, and 8% in 2014), whereas tandem auto-transplants increased for brain tumors (57% in 2008 and 77% in 2014). Allo-transplants from relatives other than HLA-identical siblings doubled between 2008 and 2014 (3% in 2008 and 6% in 2014). These trends will be monitored in future reports of transplant practices in the United States.

Total Marrow Irradiation (TMI) Based T- Replete Myeloablative Haploidentical Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in Second Complete Remission: A Single Center Experience of Two Cases

Total Marrow Irradiation (TMI) Based T- Replete Myeloablative Haploidentical Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in Second Complete Remission: A Single Center Experience of Two Cases

Outcomes of Allogeneic Transplantation in Patients Aged ≤ 60 Years with Acute Myeloid Leukemia in Second Complete Remission: A CIBMTR ® Cohort Analysis

Introduction: Allogeneic hematopoietic cell transplantation (HCT) has demonstrated survival benefit in younger patients with intermediate/high-risk acute myeloid leukemia (AML), while data for older patients transplanted in CR2 in particular are limited. The purpose of the presented study was to retrospectively investigate within the CIBMTR database parameters that influence post-transplant outcome for patients aged ≥60 undergoing allogeneic HCT for AML in CR2.Methods: Using the CIBMTR database, patients aged ≥60 years with AML in CR2 who underwent HCT between 2001 and 2012 were identified. A number of patient, disease and transplant-related variables were analysed, and outcomes studied included overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM).Results: Intotal, 196 patients with AML in CR2 met the eligibility criteria for this study. Median follow-up of survivors was 73 (6-123) months. Median age at transplant was 64 years (range 60-78), 81 patients (41%) were female. Seventy one percent had a Karnofsky performance status ≥90%. De novo AML was diagnosed in 147 patients (75%). Concerning cytogenetics at diagnosis (SWOG/ECOG), 16 patients (8%) were favorable, 133 (68%) were intermediate and 17 (9%) were unfavorable risk, while 30 patients (15%) had missing data. Concerning duration of CR1, 48 patients (24%) demonstrated <6 months, 48 patients (24%) 6-12 months and 74 patients (38%) ≥12 months, missing data in 26(13%). Myeloablative conditioning regimens were used in 37 patients (19%). Fifty-eight patients (30%) had matched sibling donors, 99 (51%) were well-matched unrelated and 39 (20%) were partially matched unrelated. Peripheral blood stem cells were used in 171 patients (87%), 58 patients (30%) received in vivo T-cell depletion.Univariate analysis demonstrated a 3-year OS of 42% (95% confidence intervals [CI] 35-49), LFS of 37% (95% CI 30-44), NRM of 25% (95% CI 19-32), and CIR of 38% (95% CI 31-45). Cumulative incidence of acute GvHD at 100 days was 33% (95% CI 26-40) while chronic GvHD at 3-years was 54% (95% CI 46-61).Cytogenetics was the only independent risk factor (relative risk [RR] 1.14 (95% CI 0.59-2.19) and 2.32 (95% CI 1.05-5.14) for intermediate and unfavorable risk respectively) for survival in multivariate analysis. For CIR, cytogenetic risk was the predominant prognostic factor (RR 1.10 (95% CI 0.47-2.56) and 2.98 (95% CI 1.11-8.00) for intermediate and unfavorable risk respectively, p=0.008). A higher NRM was observed with bone marrow graft source (RR 2.75, p=0.002) and male gender (RR 2.04, p=0.02).Conclusion: This study demonstrates the potential of long-term remissions with HCT in selected older patients with AML in CR2. Patients with adverse risk cytogenetics had very poor outcome due to higher risk of post-transplant relapse, and novel strategies are required for these patients. DisclosuresGupta:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding.

Encouraging Outcomes of Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Patients with Acute Lymphoblastic Leukemia in Second Complete Remission

[Background] We have been performing reduced-intensity stem cell transplantation (RIST) to avoid preconditioning-related complications. However, the effectiveness of RIST in pediatric patients with acute lymphoblastic leukemia (ALL) remains to be clarified.[Methods] We retrospectively reviewed 37 pediatric patients with ALL in second complete remission (CR2) who underwent first allogeneic hematopoietic stem cell transplantation (allo-SCT) between 1993 and 2012 in our institute. We compared the outcomes of RIST with those of myeloablative stem cell transplantation (MAST).[Results] The median age at allo-SCT was 9 years (range, 1 to 18 years). There were 33 B-lineage ALL, 3 T-lineage ALL, 1 lineage unknown ALL, and none of Philadelphia chromosome-positive ALL. Sixteen patients received HLA-matched bone marrow (7 related; 9 unrelated), 12 HLA-mismatched bone marrow (11 unrelated; 1 HLA haploidentical related), 4 cord blood, and 5 CD34 positive peripheral blood stem cells (HLA haploidentical related). In all patients, the 5-year overall survival (5y-OS) rate and the 5-year event free survival (5y-EFS) rate were 75.1% and 56.5%, respectively.Seven patients underwent RIST and 30 patients underwent MAST. The median follow-up durations of RIST and MAST groups were 3.3 years (range, 0.9 to 8.2 years) and 11.3 years (range, 0 to 21.2 years), respectively. The 5y-OS rates in RIST and MAST groups were 85.7% and 59.8%, and the 5y-EFS rates were 71.4% and 53.3%, respectively. The 5-year cumulative transplant-related mortality (TRM) rates in RIST and MAST groups were 0% and 31.0%, and the 5-year cumulative relapse rates were 28.6% and 24.3%, respectively.[Discussion] In our series, the cumulative relapse rate in RIST group was similar with that in MAST group, and the cumulative TRM rate in RIST group was lower than that of MAST group. Therefore, both of the 5y-OS and the 5y-EFS rates in RIST group seem to be better than those in MAST group. The outcomes of RIST in our series do not seem to be poorer. Although further studies are needed because of the small size of patients and short follow-up duration, RIST can be considered as the first transplantation for pediatric patients with ALL in CR2. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Autologous Is Superior to Allogeneic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukemia in Second Complete Remission

To identify favored choice of transplantation in patients with acute promyelocytic leukemia (APL) in second complete remission, we studied 294 patients with APL in second complete remission (CR2) receiving allogeneic (n = 232) or autologous (n = 62) hematopoietic cell transplantation (HCT) reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR) from 1995 to 2006, including 155 with pre-HCT PML/RAR∝ status (49% of allogeneic and 66% of autologous). Patient characteristics and transplantation characteristics, including treatment-related mortality, overall survival (OS), and disease-free survival, were collected and analyzed for both univariate and multivariate outcomes. With median follow-up of 115 (allogeneic) and 72 months (autologous), 5-year disease-free survival (DFS) favored autologous with 63% (49% to 75%), compared with allogeneic at 50% (44% to 57%) (P = .10). OS was 75% (63% to 85%) versus 54% (48% to 61%) (P = .002), for autologous and allogeneic transplantation, respectively. Multivariate analysis showed significantly worse DFS after allogeneic HCT (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.16 to 3.06; P = .011) and age > 40 years (HR, 2.30; 95% CI, 1.44 to 3.67; P = .0005). OS was significantly worse after allogeneic HCT (HR, 2.66; 95% CI, 1.52 to 4.65; P = .0006); age > 40 (HR, 3.29; 95% CI, 1.95 to 5.54; P < .001), and first complete remission < 12 months (HR, 1.56; 95% CI, 1.07 to 2.26; P = .021). Positive pre-HCT PML-RAR∝ status in 17 of 114 allogeneic and 6 of 41 receiving autologous transplantation did not influence relapse, treatment failure, or survival in either group. The survival advantage for autografting was attributable to increased treatment-related mortality (TRM) in the allogeneic group of 30% compared to 2% in the autologous group, in addition to the added mortality associated with GVHD. We conclude that autologous HCT yields superior OS for APL in CR2. Long-term DFS in autologous recipients, even with minimal residual disease–positive grafts, remains an important subject for further study.

Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

PurposeThe survival rate for childhood acute lymphoblastic leukemia (ALL) has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT) offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR).MethodsFifty-three ALL patients (42 men, 79%) who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%). Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD), relapse, 1-year transplant-related mortality (TRM), disease-free survival (DFS), and overall survival (OS).ResultsCumulative incidences of acute GVHD (grade 2 or above) and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2±6.8% and 48.3±7%, respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010). The rates of relapse and 1 year TRM were 28.9±6.4% and 26.4±6.1%, respectively, and unrelated donor HSCT (P=0.002) and HLA mismatch (P=0.022) were significantly correlated with increased TRM in univariate analysis.ConclusionIn this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

Reduced Intensity Versus Standard Myeloablative Conditioning in Patients With Acute Myeloid Leukemia in Second Complete Remission

Reduced Intensity Versus Standard Myeloablative Conditioning in Patients With Acute Myeloid Leukemia in Second Complete Remission

Influenza A H1N1 Virus Infection in Two Hematopoietic Stem Cell Transplant Recipients.

Abstract 1169Poster Board I-191In April 2009, a novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in Mexico. Since then, several cases have been reported, with subsequent cases observed in many other countries. Clinical presentation may range from mild symptomatic patients to cases of severe clinical presentation and death due to pneumonia and respiratory failure. Definition of high risk groups are thought to be similar to those defined for seasonal influenza, including young children and elderly patients, pregnant women and patients with chronic medical conditions, especially immunocompromised hosts. Hematopoietic stem cell transplant (HSCT) recipients are at high risk for infectious complications, including severe viral infections. To our knowledge, there are no reported cases of S-OIV infection in HSCT recipients to date. The clinical features and the possible consequences of this novel influenza virus in this setting remain unknown. We describe two HSCT recipients with confirmed influenza H1N1 virus infection and a benign clinical course after oseltamivir treatment. The first case is a 12 year-old male patient with diagnosis of acute myelogenous leukemia in second complete remission who underwent an unrelated umbilical cord blood transplant with two 4/6 HLA-mismatched cord blood units. Graft-versus-host disease (GVHD) prophylaxis consisted of the association of cyclosporine and mycophenolate mofetil. Additionally, he was also being treated for an invasive aspergillosis with oral voriconazole. On day+3 after transplant, he developed fever, rhinorrhea, and dry cough. A nasal wash and a nasal swab were positive for influenza A by direct immune fluorescence and for influenza A H1N1 by real-time polymerase chain reaction (RT-PCR). Computed tomography of the nasal sinus and thorax were unremarkable. Oseltamivir therapy (75 mg po twice daily for 10 days) was initiated the same day with progressive improvement of symptoms. Oseltamivir was well tolerated and there was no interference with serum levels of cyclosporine. The second case is a 30 year-old female patient with gray zone non-Hodgkin lymphoma in relapse after autologous stem cell transplant that underwent an HLA-matched related HSCT in September 2008. She relapsed 6 months after the transplant. Cyclosporine was withdrawn. Ten days later, she developed fever rhinorrhea, and myalgia. Influenza A H1N1 was confirmed by RT-PCR of a nasal wash specimen. Treatment with a 5-day course of oseltamivir (75 mg po twice daily) was initiated and the patient had a favorable clinical course, with no complications. These two cases of confirmed influenza H1N1 virus infection in HSCT recipients with a benign clinical course highlight the need for a better understanding of the clinical course and management of this novel viral agent in severely immunocompromised hosts. Disclosures:No relevant conflicts of interest to declare.

Outcome of allogeneic hematopoietic stem cell transplantation for children with acute myelogenous leukemia in second complete remission: Single center experience

We reviewed 26 consecutive patients with AML who were transplanted in second CR2 between 1994 and 2005. The most common conditioning regimen was CY and TBI. Median age at transplant was 8.9 yr (range 2.2-18.2). Nine patients received related donor, 16 patients received unrelated donors, and one patient received unrelated cord stem cells. Acute grade III-IV and chronic extensive GVHD occurred in eight (30%) and nine (35%) patients, respectively. Six patients (23%) relapsed, four of them died. Six patients (23%) died from TRM. Estimate of three-yr EFS was 0.53 (95% CI; 0.34-0.72). Including the two relapsed patients who were salvaged by DLI and second transplantation, three-yr OS was 0.61 (95% CI; 0.41-0.78) with a median follow-up of three and a half yr (range 1.5-11.2 yr). When entering remission, children with relapsed AML have a reasonable survival with HSCT, but relapse and TRM remain a concern.

Hematopoietic Cell Transplantation for Children with Acute Lymphoblastic Leukemia in Second Complete Remission: Similar Outcomes in Recipients of Unrelated Marrow and Umbilical Cord Blood versus Marrow from HLA Matched Sibling Donors

Transplant decisions for children with acute lymphoblastic leukemia (ALL) in second complete remission (CR2) are often based on the type of available donor. In many cases, allogeneic hematopoietic cell transplantation (HCT) is considered only if a human leukocyte antigen (HLA) matched sibling donor (MSD) is available. The role of unrelated donor (URD) HCT in this patient population is not well established. As advances in supportive care and donor selection have improved, the use of URD HCT in such patients should be reevaluated. We analyzed the outcomes of 87 consecutive children with ALL in CR2 who underwent allogeneic HCT at the University of Minnesota between 1990 and 2007. Donor sources included MSD bone marrow (n = 32), well and partially matched (M, n = 18) and mismatched (MM, n = 16) URD bone marrow and URD umbilical cord blood (UCB, n = 21). Although the incidence of neutrophil recovery was similar in all groups, the overall incidence of grades II-IV acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) was 37% and 9%, respectively, with a higher incidence of aGVHD in recipients of URD grafts. Leukemia-free survival (LFS) at 5 years was lower in recipients of MM-URD grafts, but was comparable in all other groups. Although relapse at 5 years was highest in recipients of MSD (50%), results were not significantly different compared to recipients of M-URD (17%), MM-URD (6%), and UCB (33%) (P = .17). The development of grades II-IV aGVHD and a first remission >3 years were associated with a lower risk of relapse (relative risk [RR] 0.2, P = .03; RR 0.2. P = .01 respectively). Together, these results support the continued investigation of URD HCT for ALL in CR2, and suggest the timing of HCT in these children should be based primarily on the risk of relapse with conventional chemotherapy and not on the type of donor available.

Allogeneic Stem Cell Transplantation for Children With Acute Myeloid Leukemia in Second Complete Remission

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for patients with relapsed acute myeloid leukemia. In this retrospective, multicenter study, we analyzed the outcome of 63 children (median age, 7 y; range, 0.2 to 17) who received unmanipulated allo-HSCT in second complete remission. Either a matched family donor or an unrelated donor was used in 29 (46%) and 34 (54%) patients, respectively. The stem cell source was bone marrow in 53 children (84%), peripheral blood in 7 (11%), and cord blood in 3 patients (5%). Preparative regimen included total body irradiation in 25 patients (40%). The 5-year estimates of overall survival and leukemia-free survival were 53% [95% confidence interval (CI) 39-66] and 49% (95% CI 35-63), respectively, whereas the cumulative incidence of relapse and transplant-related mortality (TRM) were 26% (95% CI 16-41) and 25% (95% CI 15-40), respectively. In multivariate analysis, the use of a matched family donor predicted a better probability of LFS [relative risk (RR) 2.29, P=0.05]. Both chronic graft-versus-host disease occurrence and age at diagnosis greater than 11 years were associated with an increased TRM (RR 8.08, P=0.04 and RR 4.38, P=0.05, respectively). These results indicate that allo-HSCT is a procedure able to rescue a significant proportion of children with acute myeloid leukemia in second complete remission, especially if an human leukocyte antigen-compatible relative is employed as donor. Both leukemia recurrence and TRM contributed to treatment failure. Optimization of donor selection and of strategies for both prophylaxis and treatment of graft-versus-host disease may improve the results of unrelated donor allo-HSCT.

ALLOGENEIC HEMOPOIETIC STEM CELL TRANSPLANTATION FOR CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA IN SECOND COMPLETE REMISSION—Similar Outcomes After Matched Related and Unrelated Donor Transplant: A Study of the Spanish Working Party for Blood and Marrow Transplantation in Children (Getmon)

The authors report the results of 58 children with ALL in 2CR after related (n = 31) or unrelated (n = 27) AHSCT. Characteristics at diagnosis and initial and after relapse antileukemic treatment were similar in the related donor (RD) and the unrelated donor (UD) groups. Conditioning consisted of TBI/CY ± VP-16 for patients ≥3 years old (n = 43) and Bu/CY for the rest. Median recipient age was 8 years (range 1–17) in the RD and 9 years (range 3–14) in the UD group. Median follow-up was 54 months (range 24–80) and 52 months (range 22–85) in the RD and the UD groups repectively.The 5-year EFS probability was 43 ± 9% for the RD group and 36 ± 9% in the UD group (p =. 25). The transplant-related mortality was 16% in the RD and 37% in the UD group (p =. 016). In the RD group 36.7% of patients relapsed versus 18.6% in the UD group (p =. 05). GvHD associated with organ failure or infection caused most of the transplant-related deaths in both groups. Survivor quality of life for both groups was good (Lansky score ≤ 90).

Allogeneic Peripheral Blood Stem Cell Transplantation for Hematological Malignancies in Patients with HIV.

Optimal management of intercurrent hematological malignancy in patients with HIV, in particular the feasibility of allogeneic peripheral blood stem cell transplantation (PSCT), remains to be defined. We present our experience with allogeneic transplantation in a series of three patients with HIV. The first patient is a 38 yo man with secondary myelodysplasia in transformation to acute myeloid leukemia. He had had no AIDS-defining illnesses, and was maintained on second-line anti-retroviral therapy of Stavudine, Lamivudine and Tenofovir with an undetectable HIV viral load and CD4 count 58 cells/μL. He received a HLA-identical PSCT, conditioned with cyclophosphamide 60 mg/m2 and total body irradiation (TBI) 13.2 Gy in 6 fractions with standard graft-versus host disease (GVHD) and infective prophylaxis. Transplantation was complicated by severe BK-virus associated hemorrhagic cystitis and prolonged neutropenia with sepsis necessitating temporary withdrawal of anti-retrovirals. Engraftment occurred at day 48, and bone marrow aspirate (BMA) confirmed remission. Anti-retroviral therapy was re-introduced 12 months post-transplantation in response to a rising HIV viral load. He subsequently developed progressive renal impairment due to post-transplant glomerulopathy, but had no late infective complications and is otherwise well and in remission 21 months post-transplantation with HIV viral load 150 copies/mL and CD4 count 181 cells/μL. The second patient was a 41 yo man with multiply-relapsed acute myeloid leukemia in third complete remission. He had no AIDS-defining illnesses and was maintained on fifth-line anti-retroviral regimen of Emtricitabine, Tenofovir, and Fosamprenavir with an undetectable viral load and CD4 count 275 cells/μL. He received an HLA-Identical sibling PSCT, conditioned as above, with additional anti-microbial prophylaxis with Entecavir for HBV; Azithromycin for MAC and Ciprofloxacin for a previous Rhodococcal pulmonary infection. Transplantation was complicated by neutropenic sepsis, pericarditis, and grade 2 cutaneous GVHD. Engraftment occurred day 21; BMA confirmed remission. He remained well with no further infective complications until day 67, when he presented with drug resistant Pseudomonal sepsis, multi-organ failure and succumbed day 78. The third patient was a 24 yo man with multiply-relapsed T-cell acute lymphoblastic leukaemia in second complete remission without prior AIDS-defining illnesses, maintained on second-line anti-retroviral regimen of Tenofovir, Ritonavir, and Fosamprenavir, with an undetectable HIV viral load and CD4 count 204 cells/μL. He received an HLA-identical sibling PSCT conditioned with etoposide 60 mg/m2 and TBI 13.2 Gy in 6 fractions, with extended anti-microbial prophylaxis. This was complicated by neutropenic dental infection and grade 2 cutaneous GVHD, treated with steroid therapy. Engraftment occurred day 25; BMA confirmed remission. There were no late complications and he maintained an undetectable HIV viral load and CD4 counts >200 copies/mL. At day 101 he relapsed, was treated with palliative intent, and died day 105. This series illustrates that allogeneic transplantation is a feasible therapeutic modality for high-grade hematological malignancies in carefully selected patients. Careful optimization of HIV control, and preventive management of infective complications and drug toxicity are critical to successful outcomes.

247: Outcome of allogeneic hematopoietic stem cell transplantation for children with acute myelogenous leukemia in second complete remission, single centre experience

247: Outcome of allogeneic hematopoietic stem cell transplantation for children with acute myelogenous leukemia in second complete remission, single centre experience

Caspofungin treatment of Pneumocystis pneumonia during conditioning for bone marrow transplantation

Pneumocystis pneumonia (PCP) is a well-known compli-cation in AIDS patients, but it is also frequently diagnosedin hemato-oncological patients [1]. High-dose cotrimoxa-zole is the first-line treatment for PCP, but some patientsshow contraindications and drug resistance may appear[2]. Since Pneumocystis jirovecii cannot be cultivated invitro, mutations in the genes involved in folate metabo-lism have been investigated as a possible expression ofcotrimoxazole resistance [3], but the search for a clinicalcorrelate has so far led to equivocal results [4]. There issome doubt as to what may be the best alternative tocotrimoxazole in the treatment of PCP [5]. The presentreport refers to the use of caspofungin to treat a patientwith PCP undergoing bone marrow transplantation (BMT)in whom cotrimoxazole had to be discontinued because ofits myelotoxicity.A 45-year-old male patient with T-lymphoblastic leu-kemia in second complete remission was scheduled to re-ceive an allogeneic BMT from an unrelated HLA-matcheddonor in October 2004. In September, he was admitted tohospital because of acute respiratory failure. Subsequentexamination of bronchoalveolar lavage (BAL) led to thediagnosis of PCP, and a computed tomography (CT) scanshowed diffuse, bilateral, interstitial disease with “groundglass”parenchymaandthickeningoftheinterlobularsepta.Molecular, cultural and cytological investigations of theBAL failed to identify any other pathogen. Transbronchialbiopsy was not performed. High-dose cotrimoxazole wasstarted in combination with methylprednisolone. A bonemarrow aspirate revealed signs of an initial leukemic re-lapse that was treated with weekly vincristine and dailyoral 6-mercaptopurine, which led to a stable bone marrowblast count and the maintenance of normal peripheralhematometry.During cotrimoxazole treatment, the CT findings im-proved significantly but did not normalize, and the drugwas discontinued after 2 weeks because of patient refusal.On 7 October, the patient was discharged for personalreasons, and he continued taking oral cotrimoxazole at adaily dose of 3,840 mg. Two weeks later, a further CTscanshowed persistence of significant lung infiltrates.On 11 November, when the patient was admitted toundergoBMT,apositronemission tomography(PET)scanrevealed the presence of diffuse, active, alveolar disease(Fig. 1) and high-dose intravenous cotrimoxazole wasresumed. On 22 November, standard-dose caspofungin(70mgonthefirstday,followedby50mg/day)wasadded,and a conditioning regimen was started including thio-tepa (15 mg/kg divided into three equal doses on days −8and−7),andcyclophosphamide(50mg/kg/dayondays−4,−3 and −2). A bone marrow aspirate showed a raised butstable blast count. On 29 November, the CT findings wereunchanged, and cotrimoxazole was discontinued. On 30November, BMT was performed, with standard-dose cy-closporine-Aandmethotrexatebeingadministeredasgraft-versus-host disease prophylaxis. During pancytopenia,mixed Enterobacter/coagulase-negative Staphylococcusbacteremia was observed. Polymorphonuclear recoverywasachievedonpost-BMTday25,andplateletrecoveryonday 34, after being delayed by mild microangiopathichemolytic anemia responsive to defibrotide therapy. On22 December, a CT scan showed complete resolution ofthe lung infiltrates. On 5 January, caspofungin was dis-continued and a bone marrow aspirate showed completeremission and full donor chimerism. On 12 January thepatient was discharged. One month later, the leukemiarelapsed; a CTscan did not show any lung infiltrates.A diagnosis of PCP is frequently established in BMTrecipients,inwhomimmunodepressionmayplayaprimaryrole, and also in hematological patients receiving che-motherapy alone [1]. In such cases, cotrimoxazole mayinterfere with the possibility of delivering the subsequent