Allogeneic hematopoietic cell transplant for HIV patients with hematologic malignancies: the BMT CTN-0903/AMC-080 trial

Abstract

We set out to assess feasibility and safety of allogeneic hematopoietic cell transplant in 17 persons with HIV in a phase 2 prospective multicenter trial. The primary endpoint was 100-day non-relapse mortality (NRM). Patients had an 8/8 HLA-matched related or at least a 7/8 HLA-matched unrelated donors. Indications for transplant were acute leukemia, myelodysplasia, and lymphoma. Conditioning was myeloablative or reduced intensity. There was no NRM at 100 days. The cumulative incidence of Grades II-IV acute Graft vs Host Disease (GvHD) was 41%. At one year, overall survival was 59%; deaths were from relapsed/progressive disease (5), acute GvHD (1), adult respiratory distress syndrome (1) and liver failure (1). In patients who achieved complete chimerism, cell-associated HIV DNA and inducible infectious virus in the blood were not detectable. Blood and Marrow Transplant Clinical Trials Network 0903/AIDS Malignancy Consortium 080 was registered at www.clinicaltrials.gov as # .

INTRODUCTION

Allogeneic hematopoietic cell transplantation (alloHCT) is a safe and curative option for many patients with hematologic malignancies. Prior to the advent of effective antiretroviral therapy (ART), hematologic malignancies in people with HIV infection (HIV+) were associated with dismal outcomes with opportunistic infections being a common cause of mortality.¹ With ART, it became clear that HIV+ lymphoma patients could achieve clinical outcomes comparable to those of the general population using standard treatment regimens, including autologous hematopoietic cell transplant (HCT).^2-7

AlloHCT has not been as well studied in the HIV+ population. The impact of alloHCT on reservoirs of HIV has attracted considerable attention in the HIV cure research community. ^8-11 In particular, the only known HIV cure was achieved in one patient using alloHCT from a CCR5Δ32 homozygous donor to treat acute myelocytic leukemia.

Although retrospective data proving the feasibility of alloHCT in HIV+ patients has been reported, ^12-15 there have been no prospective multi-institution trials. Here we report the results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0903/AIDS Malignancy Consortium (AMC) 080 study. This is a phase 2 clinical trial designed to prospectively evaluate the safety and effectiveness of alloHCT for patients with HIV infection and hematologic malignancy in a multicenter setting.

PATIENTS AND METHODS

Study Design

Between May 2012 and December 2015, a prospective phase 2 multicenter trial was conducted by the BMT CTN in collaboration with the AMC. Patients with HIV infection and hematological malignancies or myelodysplastic syndromes (MDS) were treated with either reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) followed by alloHCT. RIC or MAC was at the discretion of investigator. Where feasible, an attempt was made to identify hematopoietic cell donors who were homozygotes for the CCR5Δ32 polymorphism. Graft-versus-host disease (GVHD) was treated per institutional standards.

The protocol was approved by the National Heart, Lung, and Blood Institute and local institutional review boards. All patients provided informed consent. The trial is registered at www.clinicaltrials.gov as .

Eligibility Criteria

Patients had documented HIV infection, were a minimum of 15 years of age and had acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) in first or second complete remission (CR); Int-2 or high-risk MDS with < 10% marrow blasts and no circulating myeloblasts after their most recent therapy; or Hodgkin or non-Hodgkin lymphoma beyond first CR with at least a partial response to last treatment. Patients had either an 8/8 matched related donor at HLA-A, -B, -C, (serologic typing or higher resolution) and –DRB1 (at high resolution using DNA based typing), or at least a 7/8 matched unrelated donor at HLA-A,-B, -C and DRB1 (at high resolution using DNA based typing). A 7/8 matched related donor match was permitted only if an 8/8 unrelated donor could not be identified. A secondary matching criterion was the presence of homozygosity for CCR5delta32. AlloHCT using cord blood units or T-cell depletion was not allowed. Patients with history of prior alloHCT were excluded. Patients had to meet adequate organ function. Karnofsky/Lansky performance status ≥ 70% and could not have active central nervous system disease, HIV infection resistant to all antiretroviral therapy, or opportunistic infection unresponsive to treatment.

Treatment

Four regimens were permitted for conditioning. RIC regimens were: fludarabine and busulfan (Flu/Bu), and fludarabine and melphalan (Flu/Mel). MAC regimens were busulfan and fludarabine (Bu/Flu), or cyclophosphamide and total body irradiation (Cy/TBI). GVHD prophylaxis regimens included tacrolimus/methotrexate, tacrolimus/sirolimus, and post-transplant cyclophosphamide with tacrolimus/mycophenolate. Patients receiving busulfan-containing preparative regimens were not eligible to receive tacrolimus/sirolimus. A committee reviewed individual patient’s HIV treatment history and ART options before initiation of the transplant conditioning regimen and advised changes to minimize potential drug interactions. It was recommended that ART be continued except ritonavir-containing regimens during MAC.

Outcomes

The primary trial endpoint was 100-day non-relapse mortality (NRM) i.e. death due to any causes other than relapse of the underlying malignancy. Secondary endpoints included 100-day disease status, percentage donor chimerism, hematologic function, infections, six-month overall survival (OS), incidence of acute and chronic GVHD, immunologic reconstitution, and impact of alloHCT upon measures of HIV persistence in blood including peripheral blood mononuclear (PBMC)-associated HIV DNA and infectious virus from resting CD4⁺T-cells using a quantitative virus outgrowth assay.

Patients with lymphoma underwent disease status assessments before alloHCT, at day +100, and at 1 year post-alloHCT. Lymphoma responses were assessed using the Cheson criteria for determination of CR and CR plus PR.¹⁶ Patients with acute leukemia and MDS were assessed as CR if bone marrow myeloblasts were < 5% by morphologic assessment; there were no circulating blasts; the neutrophil count was ≥ 1,000/μL; and there was the absence of previous cytogenetic or molecular abnormalities identified prior to transplantation in the bone marrow aspirate. Relapse was diagnosed as an increase in bone marrow blasts to ≥ 5% by morphologic assessment not attributed to other causes (e.g., bone marrow regeneration); or if < 5%, the reappearance of blasts with the same leukemia phenotype as present at diagnosis, the reappearance of blasts with aberrant phenotype by flow cytometry, the reappearance of leukemic blasts in the blood, the reappearance of cytogenetic or molecular markers of disease present prior to transplantation, or the development of extramedullary leukemia or leukemic cells in the cerebral spinal fluid. Disease relapse for patients with MDS was diagnosed if the above criteria for evolution into acute leukemia were satisfied; or, if there was reappearance of pre-transplant morphologic abnormalities, detected in two consecutive bone marrow specimens taken at least one month apart; or, if there was reappearance of pre-transplant cytogenetic abnormalities in at least one metaphase on each of two separate consecutive examinations at least one month apart, regardless of the number of metaphases analyzed.

Follow-up visits occurred weekly through 8 weeks post-transplant, at 100 days, 6 months, 1 year, and 2 years. Time to neutrophil recovery was defined as the first of three consecutive days of ≥ 500 neutrophils/μL following the expected nadir. Time to platelet engraftment was defined as the date platelet count was ≥ 20,000/μL for the first of three consecutive labs with no platelet transfusions during the prior 7 days. Hematopoietic function was defined as the patient achieving an absolute neutrophil count >1500/μL, untransfused hemoglobin >10 g/dL, and untransfused platelets >100,000/μL. Assessment occurred at Day 100 and 6 months. Toxicities were graded using the Common Terminology Criteria for Adverse Events, Version 4.0. Grade 3 and higher toxicities were collected. Microbiologically documented infections were collected by site of disease, date of onset, severity, and resolution from day 0 through 1 year post-alloHCT. Recovery of immunoglobulin (Ig) levels was assessed by measuring quantitative immunoglobulin levels on days +60, +180, and +365 post-alloHCT. CD4+ T cells were assessed by flow cytometry on days +60, +180, and +365 post-alloHCT. Cell-associated HIV DNA was measured by qPCR targeting a highly-conserved region of integrase in PBMC samples obtained twice before transplant, at 100, 180, and 360 days as previously described.¹⁷ The limit of detection of the assays is 3 copies of HIV DNA per million PBMC.¹⁷ The inducible infectious HIV reservoir within resting memory CD4+ T cells was measured prior to alloHCT and at one year using a quantitative viral outgrowth assay as previously described.^18-20

Acute GVHD was graded according to the BMT CTN Manual of Procedures. The time to onset of acute grades II-IV GVHD and grades III-IV GVHD was recorded, as well as the maximum grade experienced. Chronic GVHD will be scored according to the BMT CTN Manual of Procedures. The time to onset of limited and extensive chronic GVHD were recorded.

Adjudication of the primary cause of death was as previously described.²¹ Relapse was always considered to be the primary cause of death when it occurred.

Statistical Analysis

This study was a Phase II multi-center trial to assess the feasibility and safety of alloHCT in HIV-infected patients. The target sample size of 15 patients provided sufficient power for the primary endpoint to demonstrate that 100-day NRM is lower than 45%. A stopping guideline to monitor 100-day NRM using a truncated sequential probability ratio test was implemented to guard against excessive mortality during the study duration. The primary analysis consisted of estimating the 100-day NRM probability along with a 95% confidence interval using the cumulative incidence function. Neutrophil recovery, platelet recovery, relapse, acute GVHD and chronic GVHD were described using the cumulative incidence function, treating death as a competing risk. Overall survival was described using the Kaplan-Meier estimate. Other endpoints were described using descriptive statistics including proportion. Statistical analyses were performed with SAS software, version 9.4 (SAS Institute). The cumulative incidence analyses were performed with R software, version 2.15.1.

RESULTS

Patients

Seventeen HIV-infected patients with acute leukemia, myelodysplasia (MDS), NHL or classical HL were enrolled in the clinical trial and underwent alloHCT. Three additional patients enrolled on trial but were not included in the analysis as two relapsed or progressed prior to receiving conditioning and one underwent alloHCT off study. Median follow-up for survivors as of Aug 10, 2018 was 24.4 months (range: 22.1 to 27.4 months). All living patients completed 2-year follow-up. There were two significant protocol violations. One patient began the conditioning regimen on Day -10 as per institutional practice rather than Day -5 as required by the protocol. Another patient received an alternative GVHD prophylaxis rather than that required by the protocol. One patient who received a matched unrelated transplant had several hundred potential matched unrelated donors in the registry and it is likely a CCR5delta32 homozygous donor could have been identified had time permitted, but because of clinical urgency the patient and treating physicians elected to proceed with the first matched unrelated donor rather than waiting for analysis of donor CCR5 status.

Patient characteristics are presented in Table 1. All patients received T cell replete bone marrow grafts from HLA matched sibling (4) or unrelated donors (9) or single antigen mismatched sibling (3) or unrelated (1) donors. The pre-transplant HIV plasma RNA level was below the limit of quantification in 15/17 patients (88.2%). The plasma HIV RNA measurements for the two patients with detectable level were 82 and 101 copies/mL. The median pre-transplant CD4+ T-cell count was 224 CD4+/μL (range: 55-833).

Table 1.

Demographic and clinical characteristics of patients undergoing allogeneic hematopoietic cell transplantation.

Characteristics	N (%)
Total transplanted	17 (100%)
Sex
Male	17(100%)
Ethnicity
Hispanic or Latino	1(6%)
Not Hispanic or Latino	15(88%)
Unknown	1(6%)
Race
American Indian/Alaskan Native	1 (6%)
Black or African American	3 (18%)
White	11 (65%)
Unknown/Other	2 (12%)
Age, years
Median (range)	47 (25-64)
Performance status
100	4 (24%)
90	9 (53%)
80	3 (18%)
70	1 (6%)
Patient diagnosis
Acute Myeloid Leukemia (AML)	9 (53%)
Acute Lymphocytic Leukemia (ALL)	2 (12%)
Myelodysplastic Syndromes (MDS)	2 (12%)
Hodgkin's Lymphoma	1 (6%)
Non-Hodgkin's Lymphoma	3 (18%)
Leukemia Status
First Complete Remission	8 (73%)
Second Complete Remission	3 (27%)
Lymphoma Status
Complete Remission	3 (75%)
Partial Remission	1 (25%)
HIV Load
Undetectable	15 (88%)
Detectable	2 (12%)
Mean (copies/mL)	92
Pre-transplant Recipient CMV Serostatus
Positive	12 (71%)
Negative	5 (29%) (3 donors positive, 2 donors negative)
Number of Induction Chemotherapy Regimens
1	10 (59%)
2	6 (35%)
3	1 (6%)
Number of Salvage Chemotherapy Regimens
0	10 (59%)
1	6 (35%)
3	1 (6%)
HLA Match Score
7/8	4 (24%) (3 related donor, 1 unrelated)
8/8	13 (76%) (4 related donor, 9 unrelated)
Baseline CD4 Count (cells/μL)
Median	224

NRM, OS, Relapse and Causes of Death

As of August 10, 2018, 8 patients have died with a median follow-up of 24.4 months for survivors. The primary causes of death are shown in Table 2. For all three patients with NRM, death occurred more than 10 months post-transplant (Fig. 1A). The 1-year NRM rate was 11.8% (95%CI: 1.8%, 32.2%) and the 2-year NRM rate was 18.3% (95%CI: 4.1%, 40.7%). The 6-month OS was 82.4% (95% confidence interval: 54.7%, 93.9%) and 1-year OS was 58.8% (95% confidence interval: 32.5%, 77.8%) (Fig.1B). The 2-year OS was estimated to be 52.3% (95% confidence interval: 26.8%, 72.7%).

Table 2.

Primary causes of death.

Primary cause of death	N
Relapse/Progression	5
Acute GVHD	1
Adult Respiratory Distress Syndrome	1
Liver Failure	1
Total	8

Figure 1.

NRM, OS and cumulative incidence of relapse/progression post-transplant. NRM (A), OS (B), Relapse (C) for 17 patients undergoing allogeneic hematopoietic stem cell transplantation.

Five patients’ hematologic malignancies relapsed or progressed. These events occurred by six months after transplant. The 1-year rate of relapse/progression was 29.4% (95% confidence interval: 10.2%, 51.9%). At the time of transplant, all 11 patients with acute leukemia and three of four lymphoma patients were in complete remission. At day 100 post alloHCT, 13 patients (76.5%) were in complete remission, four (23.5%) had relapsed or progressive disease, and one had relapsed and died on day +95. The cumulative incidence of relapse/progression (with death considered as a competing risk) is shown in Fig.1C.

Hematologic Function Post-alloHCT and Lymphocyte Counts

All patients achieved neutrophil recovery post-transplant. The median time to neutrophil recovery was 17 (11 to 22) days. All but one patient achieved platelet recovery to 20,000/mm3. The cumulative incidence of platelet recovery to 20,000/mm3 at Day 100 was 94.1%. The median time to platelet recovery to 20,000/mm³ was 19 days. The cumulative incidence of platelet recovery to 50,000/mm3 at Day 100 was 88.2%. The median time to platelet recovery to 50,000/mm3 was 23 days. Among the 16 patients alive at Day 100, four (25%) achieved hematologic function. Among 13 patients alive at Day 180, four (30.8%) achieved hematologic function. Median CD3+ and CD4+ T-cell counts returned to baseline levels by six months after transplant and more than doubled by one year post transplant.

Chimerism

Chimerism results are shown in Table 3. Among six patients who received myeloablative conditioning and survived to six months, four had full chimerism and two mixed chimerism. Among seven patients who received reduced intensity conditioning and survived to six months, five had full chimerism and two had mixed chimerism.

Table 3.

Chimerism following alloHCT by conditioning regimen

Assessment time point post transplant	Full chimerism N (%)	Mixed chimerism N (%)	Graft rejection N (%)	Total # participants surviving/followed to the time point N (%)
Myeloablative Conditioning (n=8)
@4 weeks	4 (57%)	2 (29%)	1 (14%)	7 (100%)
@Day 100	3 (43%)	4 (57%)	0 (0%)	7 (100%)
@6 months	4 (67%)	2 (33%)	0 (0%)	6 (100%)
Reduced Intensity Conditioning (n=9)
@4 weeks	5 (56%)	4 (44%)	0 (0%)	9 (100%)
@Day 100	5 (56%)	4 (44%)	0 (0%)	9 (100%)
@6 months	5 (71%)	2 (29%)	0 (0%)	7 (100%)

Notes:

Donor chimerism based on T-cell assays: full (>95% donor cells), mixed (5-95%), or graft rejection (<5%). If T-cell assay not done, marrow samples were used. If marrow assay not done, blood samples were used.

^*One patient did not have chimerism assessed on day 28.

GVHD

Acute GVHD was reported in 7 patients: Grade II (n=4), Grade III (n=2), and Grade IV (n=1). The Day 100 Grades II-IV acute GVHD rate was 41.2% (95%CI: 17.8%, 63.4%). The Day 100 Grades III-IV acute GVHD rate was 11.8% (95%CI: 1.8%, 31.9%). Chronic GVHD was reported for three patients. All the cases were mild chronic GVHD and two of the three patients did not experience any acute GVHD. The 1 year chronic GVHD rate was 17.6% (95%CI: 4.0%, 39.2%).

Infections

At least one infectious episode was reported in 11 patients (64.7%) and the total number of infection events was 55 (Table 4). Grade 2 infections were reported in three patients and grade 3 in 8 patients. Infections were bacterial in 11 patients (35 infections), viral in 5 (14 infections), fungal in 3 (3 infections), protozoal in 1 (1 infection) and other in 1 patient. Details of CMV and fungal infection are presented in Table 4. No deaths were attributed to infection.

Table 4.

Infections

Grade	Site of Infection	Date of Onset (post transplant)	Organism	Treatment	Survival Status (primary Cause of Death)
Grade 2	Blood	39 days	CMV	ganciclovir	Died on Day 308 (ARDS)
Grade 2	Blood	119 days	CMV	foscarnet	Died on Day 194 (relapse)
Grade 2	Blood	124 days, 260 days	CMV	ganciclovir, valacyclovir	Died on Day 379 (acute GVHD)
Grade 2	Blood	36 days	CMV	valganciclovir	Died on Day 143 (relapse)
Grade 2	Tongue, Oral Cavity, and Oro-Pharynx	248 days	Candida	nystatin	Died on 344 (Liver failure)
Grade 2	Upper Airway and Nasopharynx	211 days	Pneumocystis	trimethoprim / sulfamethoxazole	Alive at Day 751
Grade 3	Feces/Stool	35 days	Candida krusei	voriconazole	Alive at Day 741

Unexpected Adverse Events

Fourteen patients (82.3%) experienced Grades 3-5 adverse events with five Grade 3, one Grade 4 and 8 Grade 5. The most commonly reported adverse events were gastrointestinal disorders, vascular disorders, chemistry/investigations, metabolism and nutrition disorders. Besides the Grades 3-5 adverse events, three patients experienced abnormal liver function. One patient developed acute renal failure and was dialyzed.

Changes in Markers of HIV Persistence in Blood

This trial allowed for search to identify potential CCR5Δ32 homozygous donors. Only one patient had a suitable CCRΔ32 donor identified. This patient experienced leukemic relapse thus precluding any long-term assessment of the impact of alloHCT upon HIV reservoirs.

The number of HIV infected cells in blood was assessed by qPCR targeting the integrase region of proviral DNA in PBMC (Figure.2). Analysis of time points where chimerism was measured in parallel with cell-associated HIV DNA showed that at every time point in 8 patients who were complete chimeras, cell-associated HIV DNA was undetectable. In contrast, in 9 measurements in 6 patients who were mixed chimeras, cell-associated HIV DNA was detected at a median of 85 copies/million (range 0-174). A quantitative viral outgrowth assay was performed in patients who survived to one year (n=8), had undetectable plasma HIV by standard clinical assay (n=6), and agreed to a large volume blood draw (n=5). Among three patients who had achieved complete donor T cell chimerism, inducible infectious virus was not detected post-transplant. In one of these patients, viral outgrowth assay had also been negative for infectious virus pre-transplant. Among two patients who demonstrated mixed chimerism at 1 year, infectious HIV remained detectable in resting CD4⁺T-cells by the quantitative viral outgrowth assay in both.

Figure 2.

Dot plot showing cell-associated HIV DNA per million PBMC in patient with complete chimerism or mixed chimerism at 100 or 180 days after transplant. Means, standard deviations, and individual data points are shown.

DISCUSSION

We undertook a prospective multi-institutional trial of alloHCT in HIV patients with a primary endpoint of 100-day NRM. There was no NRM at 100 days, or at 6 months, and therefore no evidence to suggest that NRM is prohibitive or in excess of that seen in non-HIV-infected patients. Our findings demonstrate the safety and feasibility of alloHCT for HIV+ patients who meet standard transplant criteria and who have treatment-responsive HIV infection. Our findings are consistent with a recent retrospective review of HIV patients who underwent auto or alloHCT.¹⁵ That analysis which included a similar number of alloHCT patients to ours compared patients in the database with HIV to matched patients without HIV and concluded that there was no difference in inpatient mortality rates.

The present study was too small to allow a comparative analysis of preparative or GVHD prophylaxis regimens^22,23. However, we note that T cell depletion, cord blood, and haploidentical donor strategies were not evaluated in this trial.

As in the general population undergoing alloHCT, relapse of malignancy remains the main cause of treatment failure. There is no evidence from this trial to suggest any increased risk of disease relapse in the HIV+ population; the lack of additional relapses after six months post-HCT, however, is encouraging.

A little over half of the patients (56%) achieved complete donor chimerism at four weeks which increased at 6 months (69%). There is no single benchmark for assessing complete chimerism rates post-alloHCT. Chimerism is related to both disease type and the preparative regimen. It should be noted that neither anti-thymocyte globulin nor T cell depletion were employed in any of these transplants. The limitations of the study (small sample size, heterogeneous indications for transplant, varying preparative regimens) precluded any conclusions as to whether disparities in chimerism rates exist in HIV+ patients compared to non-HIV-infected patients, but the question is important since mixed chimerism inevitably leads to HIV persistence.

There have now been two reports of virologic cure of HIV infection using CCR5Δ32 homozygous donors.^9,24 Another HIV patient with peripheral T cell lymphoma who received myeloablative alloHCT from an CCR5Δ32 homozygous donor had rapid HIV rebound after transplant with a highly replicative CXCR4-tropic HIV variant.²⁵ As noted above, the only patient in this series to receive an alloHCT from a CCR5Δ32 homozygous donor relapsed with AML early post-transplant and thus is unable to provide confirmatory evidence that alloHCT can potentially cure HIV infection. However, in patients who received CCR5 wild-type donors in this series and achieved complete donor chimerism, HIV-1 was not detected in PBMCs using a sensitive qPCR assay for proviral DNA¹⁷ and infectious virus was not detected using a quantitative viral outgrowth assay. This is consistent with earlier reports that when complete T cell donor chimerism is achieved, the number of HIV-infected cells in blood is reduced to levels below the limits of detection of these assays.^{10, 26, 27} These reductions in HIV-infected blood cells in peripheral blood do not mean that all infected cells including those with intact (replication-competent) proviruses were eliminated. Indeed, evidence from prior alloHCT patients suggests that despite undetectable HIV DNA in blood, interruption or cessation of ART can be associated with aggressive viral rebound, illustrating that blood measures are not adequate to detect all latent HIV in allograft recipients.^{10, 28, 29} In studies focused on HIV cure rather than treatment of hematologic malignancy, comprehensive analyses of memory T cells within gastrointestinal lymphoid tissue and lymph nodes have been undertaken, but such studies were not performed here. The present study is also limited by the small number of patients assessed. Nonetheless, at present, alloHCT is the only intervention that has been shown to reduce to markers of HIV persistence in blood to undetectable levels. Whether this reduction has biologic importance with regard to the course of HIV infection or the potential to achieve ART-free HIV remission is not known.

We note that one patient who received a matched unrelated donor transplant and had hundreds of potential HLA matched unrelated donors decided not to wait for further donor screening to identify a CCR5delta32 homozygous donor. Since the time of this trial, many of the registries have begun screening donors routinely and HIV-resistant donors can sometimes be identified very rapidly.

Very recently similar data have been published from an international collaboration to investigate HIV cure by stem cell transplantation.³⁰ Among 23 HIV patients undergoing allogeneic transplants, 13 died within 2 years. Among patients who achieved complete donor chimerism, there was a profound long-term reduction in the HIV reservoir. The analyses reported included investigation of HIV in lymph nodes, bone marrow and CSF in some cases.

In addition to validating the safety of alloHCT in HIV-infected patients, this trial also demonstrates the reconstitution of immunoglobulin levels and CD4+ T-cell counts post-transplant. Thus, we saw no evidence to suggest that alloHCT was associated with a long term deterioration in cellular immunity. Similarly, IgG levels recovered by one year post transplant.

The BMT CTN 0903/AMC 080 trial represents the only prospective multi-institutional study of the use of alloHCT in HIV+ patients. The safety outcomes in this trial coupled with previously published alloHCT data indicated that HIV infection should not be considered a contraindication to alloHCT in patients who otherwise meet standard transplant inclusion criteria and in whom HIV plasma RNA can be suppressed with ART. Patients with HIV infection should also be considered appropriate for participation in clinical trials aimed at reducing relapse or progression of malignant disease and other approaches to improve overall outcomes.

Highlights.

• No 100-day allogeneic transplant-related-mortality in HIV patients.

• The HIV reservoir can no longer be detected with complete donor chimerism

• HIV should not be viewed as a contraindication to transplant