ALL In Complete Remission Research Articles

Bilateral optic nerve infiltration and leukemic retinopathy as initial signs of leukemia relapse with central nervous system involvement in an adult: a case report

BackgroundWe describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement.Case presentationA 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased.ConclusionsTo the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.

Impact of MRD on clinical outcomes of unrelated hematopoietic stem cell transplantation in patients with Ph+ ALL: A retrospective nationwide study.

Measurable residual disease (MRD) status before transplantation has been shown to be a strong prognostic factor in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, the outcomes of unrelated hematopoietic stem cell transplantation based on the MRD status have not been fully investigated. In this retrospective study, we compared the outcomes of 715 consecutive adults with Ph+ ALL in complete remission who underwent unrelated cord blood transplantation (UCBT) (single-unit UCBT, n = 232 [4/6, 5/6, and 6/6 HLA match]), HLA-matched unrelated bone marrow transplantation (UBMT; n = 292 [8/8 HLA match]), or HLA-mismatched UBMT (n = 191 [7/8 HLA match]). In the MRD+ cohort, adjusted 3-year leukemia-free survival rates were 59.8%, 38.3%, and 55.5% after UCBT, HLA-matched UBMT, and HLA-mismatched UBMT, respectively. In the MRD- cohort, the corresponding rates were 65.3%, 70.4%, and 69.7%, respectively. The MRD+ HLA-matched UBMT group had a significantly higher risk of relapse than the MRD+ HLA-mismatched UBMT group (hazard ratio [HR] in the MRD+ HLA-mismatched UBMT group, 0.33; 95% confidence interval [CI] 0.15-0.74) and the MRD+ UCBT group (HR in the MRD+ UCBT group, 0.38; 95% CI 0.18-0.83). Furthermore, HLA-matched UBMT had a significant effect of MRD on death (HR 1.87; 95% CI 1.19-2.94), relapse or death (HR 2.24; 95% CI 1.50-3.34), and relapse (HR 3.12; 95% CI 1.75-5.57), while UCBT and HLA-mismatched UBMT did not. In conclusion, our data indicate Ph+ ALL patients with positive MRD may benefit from undergoing UCBT or HLA-mismatched UBMT instead of HLA-matched UBMT to reduce leukemic relapse.

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Adults with Ph-like ALL

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Adults with Ph-like ALL

Complement Inhibition with C1 Esterase Inhibitor Allowed Successful Transfusion of HLA Mismatched Platelets in a Transfusion Refractory Alloimmunized Patient: A Case Report

Platelet (PLT) transfusion refractoriness (PTR) is defined as the recurrent failure to obtain a satisfactory response to PLT transfusions from random donors. Prior studies have shown that up to 50% of patients with underlying hematologic disorders and a history of more than 10 PLT transfusions develop PTR. Appropriate response to PLT transfusion is defined as PLT increase of more than 30% 1 hour post-transfusion and more than 20% 24 hours post transfusion (Rebulla. Transfus Med 1993). Immune-mediated etiologies of PTR consist of alloimmunization to human leucocyte antigen (HLA) and/or human platelet antigen (HPA), most commonly caused by prior antigen exposure from transfusions, transplantation or pregnancy. There are recent data suggesting that the destruction of PLT in PTR may be related to activation of the classical pathway of complement by HLA alloantibodies bound to transfused PLT (Vo et al. Blood 2016). In vitro data has shown that for the management of patients with PTR, HLA antibodies identified by a C1q-based assay are more clinically relevant than antibodies identified by the IgG binding-based method, as complement fixation, and not binding alone, is the essential step for PLT destruction (Fontaine, Transfusion 2011). Autoantibodies against PLT antigens have been shown to trigger activation of complement via the classical pathway resulting in the deposition of complement on the platelet surface. C1 esterase inhibitor (C1-INH) is one of the serine protease inhibitors and regulates the classical pathway of complement by blocking C1 esterase and is approved by FDA for prophylactic and therapeutic use in hereditary angioedema. (Zeerleder. Semin Thromb Hemost 2011, Zuraw et al. NEJM 2010) C1-INH has been reported to result in immediate platelet count improvement in patients with refractory immune thrombocytopenia (Roesch. Am J Hematol Oncol. 2016) and has also been successfully utilized to inhibit hemolysis after transfusion of antigen mismatched PRBCs (Warner. ASH 2016). Based on these data, we hypothesized that the prophylactic administration of a C1 would interrupt activation of the classical complement pathway and would overcome severe life threatening PTR by reducing the destruction of transfused PLTs in the _INH reticuloendothelial systemA 75yo female with a history of pre-B ALL in complete remission, developed treatment related AML. During therapy for AML she developed PTR. Her PLT recovery 24 hours after transfusion was consistently below 20% and her PLT count remained critically low (< 10 k/mcL). Further investigation with indirect PLT screen demonstrated plasma reactivity with 10 of 10 HLA-typed PLT in the Solid Phase Adherence Assay. Given the critical clinical circumstances, it was decided to administer the commercially available C1-INH, Berinert®, prior to transfusion of HLA mismatched PLT. After the first dose of 2000u C1-INH and transfusion of HLA mismatched PLT the 1 hour post transfusion PLT count increased to 33 k/mcL from baseline of 4 k/mcL. A second dose of C1-INH was given before administering the next PLT transfusion for a PLT count of 7 k/mcL and the 1 hour post transfusion PLT count was 37 k/mcL. This treatment strategy was continued for 2 months. The patient received a total of 13 doses of C1-INH. The mean PLT count nadir prior to and after initiation of C1-INH was 7 k/mcL and 23 k/mcL, respectively.We present the first reported case utilizing prophylactic inhibition of complement with C1-INH prior to PLT transfusion in a highly alloimmunized patient. With this strategy, the patient achieved clinically significant improvement in PLT response post transfusions. Furthermore, the mean of the nadir PLT counts while on C1-INH were higher. These two findings are clinically important as studies have shown significant reduction in spontaneous bleeding risk with PLT above 10 k/mcL. We hypothesize that inhibiting the activation of complement via the classical pathway could potentially be effective in prevention of the destruction of transfused PLTs in patients who are PTR secondary to alloimmunization. Future directions would include clinical trials exploring complement inhibition's role in treating PTR and possibly preventing alloantibody formation in heavily transfused patients. [Display omitted] DisclosuresBroome:Alexion Pharmaceuticals: Honoraria; TrueNorth Therapuetics: Honoraria.

Interim Results of a Multicenter, Single-Arm Study to Assess Blinatumomab in Adult Patients (pts) with Minimal Residual Disease (MRD) of B-Precursor (BCP) Acute Lymphoblastic Leukemia (GMALL-MOLACT1-BLINA)

Interim Results of a Multicenter, Single-Arm Study to Assess Blinatumomab in Adult Patients (pts) with Minimal Residual Disease (MRD) of B-Precursor (BCP) Acute Lymphoblastic Leukemia (GMALL-MOLACT1-BLINA)

Genetic Characteristics and Clinical Outcomes of T-Cell Acute Lymphoblastic Leukemia; Myeloid-Suppressive Therapeutic Approach Based on Allogeneic Hematopoietic Cell Transplantation May Benefit in Early T-Cell Precursor Acute Lymphoblastic Leukemia

Background: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk subgroup of T-cell ALL. T-cell ALL is characterized by poorer survival outcomes compared to B-cell ALL, but the optimal treatment strategies are not well elucidated yet. Aim: We performed integrative genetic analyses and tried to find important genetic events in T-cell ALL. We also identified clinical outcomes of T-cell ALL including ETP-ALL subgroup, which were treated with myeloid-suppressive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT) for post-remission therapy. Methods: We enrolled 40 adult patients with T-cell ALL for analyses of gene mutations and treatment outcomes. Integrative genetic analyses were performed with massive parallel sequencing for NOTCH1, FBXW7, DNMT3A, PHF6, RUNX1, KRAS, NRAS, PTEN, GATA3, EZH2 and SH2B3, and multiplex ligation-dependent probe amplification (MLPA) for copy number alterations of several genes. Among them, quantification of CDKN2A and CDKN2B mRNA expression was performed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). All were treated with myeloid-suppressive chemotherapy which consisted of hyper-fractionated cyclophosphamide (300 mg/BSA, every 12 h, days 1-3), vincristine (1.4 mg/BSA, maximum dose 2 mg, days 4 and 11), daunorubicin (45 mg/m2, days 4 and 11), and dexamethasone (40 mg, days 1-4 and days 11-14) for remission induction, followed by consolidation with high-dose cytarabine (2 g/BSA, every 12 h, days 1-5) and mitoxantrone (12 mg/BSA, days 1-2). Above two anthracycline-intensified regimens were alternatively used for further consolidation. For patients not in complete remission (CR), mitoxantrone (12 mg/BSA, d 1-4), cytarabine (2 g/BSA, every 12 h, d 1-4) and etoposide (100 mg/BSA, d 5-7) were used for reinduction. Our strategy for T-cell ALL in CR was to offer allo-HCT according to the donor availability. Results: We identified 16 patients with ETP-ALL presenting 1 or more stem cell or myeloid marker with absence of CD1a, CD5, and CD8 expression, and 24 patients with non-ETP-ALL. For genetic mutation profiles between ETP-ALL and non-ETP-ALL, we found DNMT3A was more frequently observed in ETP-ALL (25% vs. 12.5%), while FBXW7 (33.3% vs. 6.2%) and RUNX1 (25.0% vs. 0.0%) were more frequently observed in non-ETP-ALL. We also observed that CDKN2A expression was significantly higher in ETP-ALL (0.053 vs. 0.001, p=0.017). In total, 33 (82.5%) patients achieved CR (24 after induction, 9 after reinduction) and their estimated 5-year overall survival (OS) was 31.3% with median survival of 18.9 months. All 16 (100%) patients with ETP-ALL achieved CR (13 after induction, 3 after reinduction), while non-ETP-ALL in 17 (70.8%, 11 after induction, 6 after reinduction) patients. Estimated 5-year OS of ETP-ALL was 41.7% and non-ETP-ALL was 24.3% (p=0.135). Finally, 12 (75.0%) out of 16 ETP-ALL and 11 (45.8%) out of 24 non-ETP-ALL underwent allo-HCT in CR and their 5-year OS was 55.6% and 45.5%, respectively. Conclusion: Our data suggested different genetic predisposition between ETP-ALL and non-ETP-ALL and myeloid-suppressive chemotherapy showed a good CR rate in ETP-ALL. Myeloid-suppressive chemotherapy induced CR followed by post-remission allo-HCT can be a good solution for improving poor survival outcome of ETP-ALL. Disclosures Kim: Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Amgen: Honoraria; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Honoraria; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria; BL &amp; H: Research Funding. Lee:Alexion: Consultancy, Honoraria, Research Funding; Achillion: Research Funding.

A phase II study of myeloablative allogeneic hematopoietic stem cell transplantation (aHSCT) for acute lymphoblastic leukemia (ALL) in older patients using fludarabine and total body irradiation (Flu/TBI).

TPS7069 Background: Older adults with ALL have poor survival outcomes. Although aHSCT can be curative when used as consolidation after complete remission (CR), advanced age, limited performance status, and comorbidities are risk factors for increased non-relapse mortality (NRM) after myeloablative aHSCT. The 1-year disease free survival (DFS) for patients ≥ 40 years who receive an aHSCT for ALL is often estimated to be 40-50%. Previous studies have demonstrated the efficacy of TBI-based regimens in adults with ALL when combined with cyclophosphamide (Cy). Reduced intensity conditioning for ALL patients has fallen out of favor due to high relapse rate forfeiting the benefit of reduced NRM. High-dose Cy is, however, associated with cardiac, hemorrhagic and hepatic toxicities. Fludarabine (Flu) has emerged as a safer substitute of Cy (e.g. Flu/Bu replacing Bu/Cy) with favorable toxicity profile. Given the efficacy of TBI-based regimens in ALL, we hypothesized that a myeloablative regimen of Flu/TBI (12 Gy) is almost as effective as Cy/TBI 12 Gy in older adults with ALL undergoing aHSCT, but with less NRM confering survival benefit over Cy/TBI 12 Gy. Methods: This study is a single center, single-arm phase II clinical trial of Flu 40 mg/m2 IV daily (days -7 to -4) and TBI 2 Gy X2 (days -3 to -1) as myeloablative conditioning for older adults (≥40 years old) or younger adults with significant comorbidities with ALL. Patients aged 40-65 years with ALL in CR, KPS ≥ 70, adequate organ function, and having HLA-matched sibling or unrelated donor will be eligible. The primary endpoint of the study is 1-year DFS post-transplant. Secondary endpoints include 1-year overall survival (OS), incidence and severity of acute and chronic GVHD, immune reconstitution and regimen related toxicity. The study has just finished accrual (January 2019) enrolling a total of 16 patients. This number of patients was pre-determined to give a probability ≤ 0.05 of concluding that the 1-year DFS rate exceeds 45%, and a probability of at least 0.80 of concluding that the 1-year DFS rate exceeds 45% (expecting 1-year DFS of 75%). Clinical trial information: NCT01991457.

Phase II Study of Blinatumomab in Patients with B-Cell Lineage Acute Lymphocytic Leukemia with Positive Minimal/Measurable Residual Disease

Phase II Study of Blinatumomab in Patients with B-Cell Lineage Acute Lymphocytic Leukemia with Positive Minimal/Measurable Residual Disease

Updated Long-Term Results of a Randomized Comparison of Prophylactic and Pre-Emptive Imatinib Following Allogeneic Stem Cell Transplantation for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)

Abstract 247 Background:The presence of minimal residual disease (MRD) after allogeneic stem cell transplantation (SCT) for Ph+ ALL is highly predictive of eventual relapse. Imatinib (IM) has very limited efficacy in hematologic relapse of Ph+ALL, but may prevent leukemia recurrence if started when the leukemia burden is still very low and detectable only by molecular techniques. The optimal time for starting IM post transplant and the prognostic relevance of different bcr-abl transcript levels in relation to time after SCT have not been established. Aims:To determine the impact of post-transplant IM, given either prophylactically or after detection of bcr-abl transcripts (pre-emptively), on the overall incidence of MRD, remission duration, long-term treatment outcome and tolerability in pts. who underwent SCT for Ph+ALL in complete remission. Study Design:In a prospective, randomized multicenter trial, previously transplanted Ph+ ALL pts. (n=55) were assigned to receive imatinib prophylactically (n=26) or pre-emptively (n=29). SCT was performed in CR1 in 23 pts. and 27 pts. in the two groups, respectively. Five pts.were transplanted in CR2. Serial assessment of bcr-abl transcripts was performed by quantitative RT-PCR and additionally by nested-RT-PCR if the sensitivity of the qRT-PCR was below the quantitative range. Confirmatory testing of a second independent sample was not required, to reduce the risk of treatment delays. Samples were considered PCR negative only if the ABL copy number exceeded 104. Imatinib administration was scheduled for one year of continuous PCR negativity. Results:IM was started in 24/26 pts. allocated to prophylactic IM and in 14/29 pts. in the pre-emptive arm. The majority of pts. received IM 400 mg/d (26/38 pts.), the other 12 pts. 600 mg IM daily. IM was started a median of 48 d after SCT in the prophylactic arm and 70 d after SCT with pre-emptive therapy. After a median follow-up of 30 mos. and 32 mos., respectively, 82% and 78% of pts. are alive in ongoing CR, 4 pts. died in CR. Five pts. transplanted in CR1 and 2/5 pts. transplanted in CR2 have relapsed (median follow-up 9 mos. and 10.5 mos., respectively). The frequency of MRD positivity was significantly lower in pts. assigned to prophylactic imatinib (10/26; 40%) than those in the pre-emptive treatment arm (20/29; 69%) (p=0.046 by chi2 test). Only 9 of 29 pts. assigned to pre-emptive imatinib remained continuously PCR negative after SCT, with a median follow-up of 32 months (18–46 months) after SCT. The median duration of sustained, uninterrupted PCR negativity after SCT is 26.5 months with prophylactic and 6.8 months with pre-emptive administration of imatinib (p=0.065). The probability of remaing in CHR after SCT was significantly lower in partients who remained MRD negative after SCT (p=0.0002). Analysis of the kinetics of molecular relapse showed that detection of bcr-abl transcripts within 100 days of transplant, despite rapid initiation of IM, was associated with a significantly inferior EFS compared to first detection of MRD positivity more than 100 days after SCT. IM was discontinued prematurely in 54% pts. receiving imatinib prophylactically and in 64% of pts. receiving imatinib pre-emptively, mostly due to gastrointestinal toxicity. Accordingly, the time to IM discontinuation was 245 d and 191 d in the prophylactic and the pre-emptive treatment arms, respectively. Despite this early discontinuation rate, overall survival in the two treatment groups was 80% and 74.5% after 5 years, with no significant difference by log rank test (p=0.84). Conclusions:Prophylactic administration of imatinib significantly reduces the incidence of molecular relapse after SCT. Both interventional strategies are associated with a low rate of hematologic relapse, durable remissions and excellent long-term outcome in patients with Ph+ ALL. The presence of MRD both prior to and early after SCT identifies a small subset of patients with a poor prognosis despite post-transplant imatinib, and warrants testing of alternative approaches to prevent hematologic relapse. Disclosures:Schuld:Novartis: Employment. Goekbuget:Micromet: Consultancy. Ottmann:Novartis Corporation: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding.

Simultaneous Transplantation of Three Cord Blood Units in Adults with High Risk Acute Leukemia.

Adult patients with high risk acute leukemia have allogeneic hematopoietic transplantation as the only therapeutic option with some curative potential. Those who lack related or unrelated marrow donor are deprived of this possibility. Patients of smaller size may benefit from the transplantation of single cord blood unit, but for heavier patients two units may be required as reported by Barker et al. (Blood 2005; 105:1343). For very heavy patients even more units would be necessary to approximate the preferred threshold of 37 millions of cells per kilo. Moreover, cord blood units have variable size and it is always a risk that the only HLA-matched units for given patients would be small and two units would not provide adequate number of cells even for patients of moderate size. This is yet another argument to attempt transplantation of more than two units. Three patients have so far been included. Patient No 1 was 24 yrs old male (body weight 87 kg) with resistant AML transplanted with 3 units (two matched at 4/6 HLA antigens, one matched at 3/6 HLA antigens) on March 29, 2004 following conditioning with standard BuCy4 + ATG regimen. This patient died d. +42 of Gram negative sepsis without hematopoietic reconstitution. Patient No 2 is 22 yrs old male (body weight 100 kg) with Ph+ ALL in complete remission, who was transplanted on October 11, 2004 with 3 units (two matched at 4/6 HLA antigens, one matched at 3/6 antigens) following conditioning with TBI, etoposide and ATG. This patient had neutrophil recovery d. +27, and platelet recovery d. +49. He is alive and well 9 months after the transplant fully chimeric with progeny of only one of transplanted units. Patient No 3 is 31 yrs old male (body weight of 100 kg) with ALL relapsed after autologous BMT with multiple cytogenetic abnormalities. He was transplanted May 24, 2005 with 3 units (one matched at 5/6 HLA antigens, two matched at 4/6 HLA antigens) following conditioning with treosulfan, cyclophosphamide, melphalan and ATG (he earlier received TBI prior auto-BMT). Patient obtained neutrophil recovery d. +36 and as of d.+60 still has low platelets. No data on chimerism are yet available. These data confirm that transplantation of more than two cord blood units is feasible and may provide therapeutic option for patients with high risk leukemia who lack marrow donor and for whom two cord blood units do not provide sufficient number of cells. As in the case of the transplantation of two units patients seem to be reconstituted with progeny of only one “winning” unit.

Impact on Transplant Outcome of Karyotyping Analysis in Apheresis Products for Autologous PBSC Transplantation in De Novo Acute Leukemias (AL).

Autologous stem cell transplantation as consolidation therapy for de novo AL is able to improve long-term survival especially after second complete remission (CR). In this study, we retrospectively analyzed the karyotyping results performed in 79 out of 101 harvested autologous PBSC from 38 de novo AML patients and 8 de novo ALL in CR. We secondly, analyzed their impact on overall survival (OS) and event-free survival (EFS) post-transplant. All patients had abnormal medullar karyotype at diagnosis. We determined two groups of patients: (1) group 1 with chromosomal abnormalities in harvested PBSC included 10 AML [4 males and 6 females, median age: 53 years (45–66.5)] with at diagnosis 3 favorable, 4 intermediate and 3 unfavorable-risk karyotype ; 2 M0, 3 M2, 1 M3, 2 M4, 2 M5 according to Fab classification ; and 9 autotransplanted patients in CR1 and 1 in CR2 and (2) group 2 without any chromosomal abnormalities in harvested PBSC including 27 AML+ 9 ALL [22 males and 14 females, median age : 44 years (19–70)] ; 1 M0, 1 M1, 4 M2, 5 M3, 11 M4, 5 M5 with at diagnosis 18 favorable prognosis, 1 intermediate and 8 unfavorable-risk karyotype ; among ALL patients, 7 B ALL and 2 T ALL and at transplant, 29 autotransplant in CR1, 6 in CR2 and 1 in CR3]. Cytapheresis products collected contained a median number of 7.7x 108/Kg (5.2–17.3) and 6.79x108/Kg (1.26–16.4) mononuclear cells and 19x106/Kg (3–43) and 20.5x106/Kg (1–4O) CD34+ cells in group 1 and in group 2 respectively. All PBSC harvested were reinfused. Conditionning regimen was quite similar in the two groups and most of the patients of group 1 (60%) and group 2 (70%) received cyclophosphamide and TBI. The hematopoietic reconstitution was similar in the 2 groups [neutrophiles > 0.5 G/l: 26 days in group1 versus 19 days in group 2 (p=0,86)]. At 3 years after transplant, there was a trend for a better OS (54.7% CI 95% 40–74.8) (p=0.06) and EFS (52.5% 95%CI 39.6–74) (p=0.05) in patients who received PBSC without any chromosomal abnormalities compared to patients receiving PBSC with abnormal karyotype (OS : 30% 95% CI 11.6–77.3 ; EFS : 30% 95% CI 11.6–77.3). In conclusion, results observed from autologous harvested PBSC karyotyping are promising but a larger number of patients and a longer follow-up could enable to reach a more important significance.

Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia

Unrelated donors are commonly used for hematopoietic stem cell transplants, but graft-versus-host disease (GVHD) is a major problem. We investigated whether transplantation of purified mobilized peripheral-blood CD34(+) stem cells from unrelated donors would prevent acute and chronic GVHD in pediatric patients with leukemia and avert the need for pharmacologic immunosuppression. Thirty-one pediatric patients with acute lymphoblastic leukemia (ALL, n = 16), acute myeloid (n = 7), chronic myeloid (n = 6), or juvenile myelomonocytic leukemia (n = 2) underwent transplantation. The median purity of CD34(+) cells after positive magnet-activated cell sorting was 98.5%. Patients received a median of 8.0 x 10(6) CD34(+) cells and 6 x 10(3) CD3(+) T lymphocytes per kilogram, with no posttransplantation pharmacologic immunosuppression. Primary acute GVHD > or = grade II was seen in only 10% of patients (n = 3) and occurred only after human herpesvirus 6 (HHV 6) infection. Two patients had limited chronic GVHD. Engraftment occurred in all patients (primary engraftment, n = 26; engraftment after reconditioning, n = 5). The 2-year survival estimate was 38% for all patients and 63% for patients with ALL in complete remission. Patients with myeloid malignancies had a poor outcome. In comparison to a historical control group who received unmanipulated bone marrow, our patients had a lower incidence of GVHD (P <.001). No difference was observed in the probability of relapse or survival. Study patients with ALL in remission showed a trend toward better survival (P =.07). Transplantation of purified peripheral-blood CD34(+) cells from unrelated donors effectively minimizes GVHD and may be a good therapeutic option for patients with relapsed ALL.

ISOLATED CHOROIDAL RELAPSE DURING COMPLETE REMISSION IN ACUTE LYMPHOCYTIC LEUKEMIA (ALL)

Leukemic opthalmopathy is often reported at autopsy. Antemortem diagnosis of ocular leukemia is much less common and has been reported associated with central nervous system (CNS) &/or multiple bone marrow (BM) relapses. Leukemia was diagnosed in the choroid of a patient (pt) with ALL in complete remission (CR) during therapy. An 11 yo Black girl had null cell ALL, CaLLa and Ia positive. The CNS had no evidence of disease. Initial therapy was "standard treatment". Six mos after diagnosis the pt complained of decreased visual acuity and was found to have perivascular leukemic deposition in the ocular fundi. Fluorescein angiography and ultrasonography of the globe verified infiltration with bilateral thickening of the choroid layer. BM and spinal fluid examination were normal. Cranial radiotherapy (XRT), was administered to the whole brain, including the posterior pole of the eyes. The pt continued systemic therapy. In the 9 mos since XRT: vision has improved, fluorescein angiography shows residual pigmentary changes, ultrasonography reveals normalization of the choroid, & the pt remains in CR. Leukemic relapse of the choroid is a dangerous sanctuary not accessible to biopsy. Standard opthalmoscopic examination provides an adequate view of only the posterior pole; without dilation, peripheral lesions cannot be seen. Since peripheral fundal lesions are generally asymptomatic, opthalmologic consultation is indicated at diagnosis, periodically throughout treatment, & at termination of therapy for ALL.

Influence of different cytotoxic drugs on T and B lymphocytes in children with all during remission maintenance therapy.

The influence of four different cytotoxic drugs (MTX, CYC, 6MP, and ARA-C) on T, B, and O-lymphocytes was investigated in 20 children with ALL in complete remission during cyclic remission maintenance therapy. Each of the four drugs causes a marked reduction of the absolute number of T and B cells whereas the relative number lies within the normal range with the exception of CYC, which leads to a depression of the percentage of both T and B cells. The percentage of O cells is markedly increased by CYC and slightly increased by MTX, 6MP, and ARA-C. The data are interpreted with care since the function of the immune system and especially tumor rejection depends on the interaction between the different lymphocyte subpopulations.