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In this issue of Blood, Dhédin et al from the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) show that young to middle-aged adults who receive a pediatric-intensive chemotherapy regimen for treatment of Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-neg ALL) do not appear to require an allogeneic stem cell transplant (alloSCT) if they achieve a good response on minimal residual disease (MRD) testing after induction therapy. Patients who are not good MRD responders however, achieve better outcomes with alloSCT than their counterparts who do not receive alloSCT.

The biology and outcome of adult T-cell acute lymphoblastic leukemia are poorly understood. We present here the clinical and biologic features of 356 patients treated uniformly on the prospective trial (UKALL XII/ECOG 2993) with the aim of describing the outcome and identifying prognostic factors. Complete remission was obtained in 94% of patients, and 48% survived 5 years. Positivity of blasts for CD1a and lack of expression of CD13 were associated with better survival (P = .01 and < .001, respectively). NOTCH1 and CDKN2A mutations were seen in 61% and 42% of those tested. Complex cytogenetic abnormalities were associated with poorer survival (19% vs 51% at 5 years, P = .006). Central nervous system involvement at diagnosis did not affect survival (47% vs 48%, P = not significant). For 99 patients randomized between autograft and chemotherapy, 5-year survival was 51% in each arm. Patients with a matched sibling donor had superior 5-year survival to those without donors (61% vs 46%, chi(2), P = .02); this was the result of less relapse (25% vs 51% at 5 years, P < .001). Only 8 of 123 relapsed patients survive. This study provides a baseline for trials of new drugs, such as nelarabine, and may allow risk-adapted therapy in patients with poor-prognosis T-cell ALL.

We report on the feasibility of outpatient transplant in 716 patients undergoing autologous stem cell transplant for multiple myeloma at Mayo Clinic's site in Rochester, MN, from January 1, 2000, through October 31, 2007. We also report on the development and effect of a multidisciplinary quality initiative implemented by the Mayo Clinic Blood and Marrow Transplant Program involving physicians, nurses, pharmacists, dietitians, and financial specialists for outpatient management of patients undergoing stem cell transplant. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Analysis of hospitalization trends since inception of the program showed that 278 (39%) of the 716 patients treated completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization. We also assessed recent treatment-related mortality rates during a 33-month period after implementation of the program (between January 1, 2005, and October 1, 2007). The 100-day survival rate was 99.5% for patients with low-risk myeloma (transplant during first plateau; n=201) and 97.2% for patients with high-risk myeloma (refractory, relapsing or second or greater plateau; n=71). The overall 100-day survival rate was 98.9%. Our experience shows that outpatient transplant is feasible for all patients with multiple myeloma and results in shorter hospital stays and low treatment-related mortality rates.

Purpose: Patients with multiple myeloma who undergo autologous stem cell transplantation (ASCT) and exhibit a complete response (CR) have a superior overall survival and time to progression (TTP). High-dose cyclophosphamide is often used before ASCT for mobilization of hematopoietic stem cells. We hypothesized that cyclophosphamide might further improve CR rates in patients undergoing ASCT. We searched the Mayo Clinic myeloma transplantation database for patients who had stem cell mobilization with hematopoietic growth factor alone or cyclophosphamide and growth factor. The impact of cyclophosphamide on CR rates and TTP was evaluated., Patients and Methods: A cohort of 201 patients was identified: 127 mobilized with cyclophosphamide and growth factor and 74 with growth factor alone. There were no statistically significant differences between the 2 cohorts in regard to age, sex, b2-microglobulin level, plasma cell labeling index, cytogenetics, conditioning regimen, or disease status at time of transplantation., Results: Complete response rates were 37.4% and 41.3% (P = 0.6115) for patients mobilized with cyclophosphamide combined with growth factor and growth factor alone, respectively, and TTPs were 19.9 months and 20.9 months (P = 0.59). In a multivariate analysis for TTP, cytogenetics and CR rates were the only independent variables (P = 0.0012 and P < 0.0001, respectively)., Conclusion: We conclude that high-dose cyclophosphamide does not increase overall CR rates or improve TTP for patients with myeloma undergoing ASCT.

Absolute lymphocyte count (ALC) >or=500 cells/microl at day 15 after autologous stem cell transplantation (ASCT) is a powerful independent, prognostic indicator for survival in multiple hematological malignancies. A limitation in these studies was the selection of a single time point (day 15 post-ASCT) as the only discriminator of clinical outcome in relation to ALC recovery. We hypothesized there is a continuous and not discrete relationship between ALC recovery and clinical outcome post-ASCT in NHL. Therefore, we analyzed 274 consecutive patients who underwent ASCT for NHL between 1987 and 2001. The primary end point was to assess the impact of the kinetics of post-ASCT lymphocyte recovery>or=500 cells/microl (K-ALC) on overall survival (OS) and progression-free survival (PFS). K-ALC was a predictor of OS and PFS when the Cox proportional hazards model was used with K-ALC entered as a continuous variable (p<0.0001). Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that the K-ALC post-ASCT is associated with clinical outcome in NHL.

Primary systemic amyloidosis (AL) is characterized by multiorgan deposition of monoclonal immunoglobulin light chain. Renal involvement is common and impaired kidney function is associated with reduced median survival. Autologous stem cell transplantation (SCT) for AL achieves superior response rates compared to chemotherapy alone but patients with end-stage renal disease (ESRD) may be excluded from consideration. A treatment approach consisting of living donor kidney transplantation (LDKTx) followed by autologous SCT was developed for AL with ESRD. Eight patients underwent LDKTx with immediate graft function. Two suffered unanticipated complications post-KTx and died 10 and 3 months later. Two cases of subclinical acute cellular rejection (ACR) and one case of clinical ACR occurred--all reversible with corticosteroid. Six patients had successful stem cell harvests performed and five of these underwent SCT with satisfactory trilineage engraftment. Renal function remained stable following SCT in four and was reduced in one due to infectious and bleeding complications. One patient, who has thus far elected not to undergo SCT, has proteinuria and histologic evidence of recurrent renal amyloidosis. This experience supports the feasibility of sequential living donor KTx and autologous SCT for carefully selected patients with ESRD due to AL.

Purpose: To review the characteristics and outcomes of amyloidosis patients treated with high-dose chemotherapy and stem cell reconstitution., Subjects and Methods: Sixty-six patients with biopsy-proven amyloidosis received transplants between March 1996 and January 2001. All patients had evidence of a clonal plasma cell dyscrasia; those with nonimmunoglobulin forms of amyloidosis were excluded, as were those who had no symptoms of amyloidosis, purpura, carpal tunnel syndrome, or symptomatic multiple myeloma., Results: Amyloid was seen clinically in the kidneys (n = 45 patients), heart (n = 32), peripheral nerves (n = 11), and liver (n = 11). A monoclonal protein was found in the serum in 46 patients and in the urine in 57 patients. The median daily urinary protein loss was 4.1 g. Septal thickness, measured by echocardiography, ranged from 7 to 24 mm (median, 12 mm); 8 patients had a septal thickness > or =16 mm. Ten patients received transplants 1 year or more after diagnosis. All patients received melphalan-based chemotherapy; 17 patients were conditioned with total body irradiation. Nine patients required dialysis, 7 of whom died. Treatment-related mortality for stem cell transplantation was 14% (9/66). After a median of 25 months of follow-up after transplantation, the percentage of patients alive with one organ involved was 91% (31 of 34); two organs, 82% (18 of 22); three organs, 33% (3 of 9); and four organs, 0% (0 of 1). Hematologic responses were seen in 33 patients and organ responses in 32 patients. The 2-year actuarial survival of all patients was 70%., Conclusion: The number of organs involved before stem cell transplantation for amyloidosis is the most important factor in predicting subsequent survival. Stem cell transplantation should be considered as a treatment option for selected patients with amyloidosis.

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34+ level before apheresis compared with younger RDs (age > 60, 59 × 106/L; age 41 to 60, 81 × 106/L; age 18 to 40, 121 × 106/L; P < .001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P < .001) and higher collection volumes (52% versus 32% > 24 L, P < .001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia

BackgroundNotwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia.Methods and findingsWe prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case.Conclusionsallo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.

Background: Although the clinical outcomes of patients with TP53‐mutated acute myeloid leukemia (AML) are dismal, subsets of patients eligible for curative‐intent therapies may fare better. Because racial disparities are known to affect outcome in hematologic malignancies, the authors sought to explore disparities among patients with TP53‐mutated AML. Methods: A multicenter, retrospective study was conducted in a cohort of 340 patients who had TP53‐mutated AML (275 non‐Hispanic White [NHW] and 65 non‐Hispanic Black [NHB]) to analyze differences in treatment and outcome among NHW and NHB patients. Results: The median patient age was comparable between NHW and NHB patients (p =.76). A higher proportion of NHB patients had therapy‐related AML (31% vs. 20%; p =.08) and had co‐mutations (74% vs. 61%; p =.06). A higher proportion of NHW patients received intensive chemotherapy compared with NHB patients (47% vs. 31%; p =.02). Conversely, a higher proportion of NHB patients received low‐intensity chemotherapy (9% vs. 5.5%; p =.02) or best supportive care (22% vs. 7%; p <.001). The complete response rate (including complete responses with or without complete count recovery) was 31% versus 24.5% (p =.39) in NHW and NHB patients, respectively. Only 5% of NHB patients received allogeneic stem cell transplantation compared with 15.5% of NHW patients (p =.02). The proportion of patients who were event‐free (18.5% vs. 8.5%; p =.49) or who remained alive (24.9% vs. 8.3%; p =.13) at 18 months was numerically higher in NHW versus NHB patients, respectively, but was not statistically significant. Conclusions: The current study highlights disparities between NHW and NHB patients with TP53‐mutated AML. Efforts are warranted to eliminate treatment disparities in minority populations. Non‐Hispanic Black patients with TP53‐mutated acute myeloid leukemia (AML) were more likely to have concurrent mutations and therapy‐related AML than non‐Hispanic White patients. Non‐Hispanic Black patients who had TP53‐mutated AML received disease‐directed therapies less often compared with non‐Hispanic White patients. [ABSTRACT FROM AUTHOR]

High-dose melphalan (HD-Mel) has been successfully employed in autografting patients with multiple myeloma. An advantage of this regimen is that the total dose of Mel can be delivered in a single day, being particularly useful when non-frozen hematopoietic stem cells are employed in the autograft. All consecutive patients with R/R lymphomas, both HL and NHL studied and treated at two different centers were prospectively included in a study of ASCT employing a single dose of HD-Mel (200 mg/m2). A group of R/R HL or NHL autografted employing BEAM-like preparative regimens was constructed matched by diagnosis and age. The primary endpoint of the study was overall survival (OS), the secondary endpoint was event-free survival (EFS). Twenty-five R/R HL/NHL patients were prospectively accrued in the study. There were 8 (32%) females, 13 (52%) patients had at least 1 adverse effect: 7 (28%) developed mucositis, 5 (20%) neutropenic fever, and 6 (24%) grade IV nausea. In the HD-Mel group, median overall survival (OS) was not achieved and OS at 36 months was 71%, the transplant-related mortality being 0%. In the control group, median OS was not achieved and the 36-month OS was 76%, results not statistically significant (p 0.5). The EFS was also similar in both groups (p 0.5). HD-Mel alone is non-inferior to a BEAM-like regimen as a preparative regimen for autografting patients with R/R HL and NHL. The regimen is adequate to graft persons with non-frozen stem cells. [ABSTRACT FROM AUTHOR]

Background: Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. Methods and findings We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures—including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue—the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. Conclusions: allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs., Version of Record

High-dose chemotherapy for the management of immunoglobulin light chain amyloidosis remains an effective and viable treatment technique for selected patients with this disorder. We reviewed the medical records of 434 patients uniformly treated with high-dose chemotherapy and autologous stem cell transplant at Mayo Clinic, Rochester, Minnesota, between 8 March 1996 and 13 April 2010. Outcomes, engraftment, and predictors of early mortality were reviewed. Median survival has not been reached for the patients with a complete response, is 107 months for those with a partial response, and is 32 months for patients with no response ( p < 0.001). The only predictor of survival was cardiac stage ( p < 0.001). The hematologic response rate is predictive for organ response rates. Both hematologic and organ responses are associated with improved survival. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy and haematopoietic stem cell (HSC) transplantation is considered standard therapy in patients with chemosensitive relapsed diffuse large B cell lymphoma (DLBCL). BCNU (carmustine), etoposide, cytarabine and melphalan (BEAM) is a widely used standard DLBCL conditioning regimen. The practice of basing chemotherapy doses on body surface area (BSA) is empirical and the best biometric parameter to dose chemotherapy is unknown. Weight-based dosing has been suggested to better predict toxicity of the conditioning regimen. We correlated the dose/weight ratio with toxicity and overall outcome in a uniform cohort of 80 consecutive patients receiving HSC transplant for relapsed DLBCL at Mayo Clinic, Rochester, MN following BSA-dosed BEAM conditioning chemotherapy. Melphalan dose was used as surrogate for the entire regimen. Median age at the time of transplant was 62 (26–77) years; 65% were males. The median melphalan dose was 3·2 mg/kg (range 2·2–4·5). Patients who received >3·6 mg/kg of melphalan were more likely to have grade 3 or 4 mucositis (44·4% vs. 9·8%, P = 0·001) and prolonged hospitalization (median 13 vs. 7 d; P = 0·04). Dose/weight ratio did not correlate with cumulative incidence of relapse ( P = 0·3) or survival ( P = 0·8). Transplant physicians should consider limiting the dose of BEAM to the equivalent of 3·6 mg/kg of melphalan. [ABSTRACT FROM AUTHOR]

A third of patients with multiple myeloma (MM) have a preceding diagnosis of plasma cell proliferative disorder (PCPD), mostly monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM) or plasmacytoma. While autologous stem cell transplantation (SCT) improves survival in MM, it is not clear if patients with preceding PCPD have a different outcome. We identified 151 patients with preceding PCPD from among 804 patients undergoing SCT, and their outcomes were compared. The response rates, including complete responses, were similar between the groups. Patients with a preceding diagnosis of MGUS had longer time to progression (TTP; 27·5 months vs. 17·2 months, P = 0·01), and longer overall survival (OS) from transplant (80·2 months vs. 48·3 months, P = 0·03) compared to those with de novo myeloma. However no differences were seen among those with a preceding diagnosis of SMM or plasmacytoma in terms of TTP or OS from transplant when compared to those with de novo myeloma. Multivariate analysis indicated that the presence of MGUS prior to myeloma was prognostic for post-transplant relapse independent of other known risk factors. Patients with pre-existing MGUS prior to myeloma diagnosis have a better outcome following HDT, reflecting more indolent disease and a favourable biology than those presenting with de novo myeloma. [ABSTRACT FROM AUTHOR]

In four patients, aged 15 – 20 years, with high-risk acute myeloid leukemia (AML), high-dose samarium 153-labelled ethylenediaminetetramethylenephosphonate (153Sm-EDTMP) was used for targeted marrow irradiation before preparative chemotherapy conditioning regimens and allogeneic (three patients) or autologous (one patient) hematopoietic stem cell transplantation. The dose of 153Sm-EDTMP was 703 MBq/kg ( n = 1) or 1110 MBq/kg ( n = 3). No side-effects occurred during the 30-min infusion of 153Sm-EDTMP. Samarium – melphalan regimens were given to three patients; one had 153Sm-EDTMP – busulfan + cyclophosphamide. Total body radioactivity was below the 133 MBq safe limit before infusion of stem cells (day 14 after 153Sm-EDTMP). No hemorrhagic cystitis, nephrotoxicity or serious infections occurred. Leukocyte engraftment (white blood cell count >0.5×10 9 /l) occurred between 12 and 23 days after stem cell infusion (mean of 17 days). Complete cytogenetic and morphologic remission of AML was evident on follow-up marrow aspirate and biopsy specimens from all patients. In two of the four study patients, the disease remains in complete remission and the patients have an excellent quality of life (Eastern Cooperative Oncology Group performance status 0; no medications) and no organ toxicity more than 2 years and more than 4 years, respectively, after their blood and bone marrow transplantations. Thus, in adolescents and adults, 153Sm-EDTMP may provide a relatively simple and effective means for using irradiation to eliminate AML within the marrow. [ABSTRACT FROM AUTHOR]

Autograft absolute lymphocyte count (A-ALC) is a prognostic factor for survival in non-Hodgkin lymphoma (NHL) after autologous stem cell transplantation (ASCT). An A-ALC is dependent upon the preaphaeresis absolute lymphocyte count (PA-ALC) at the time of aphaeresis. It was hypothesised that the time interval from last chemotherapy (TILC) to aphaeresis affects PA-ALC. One hundred and sixty consecutive NHL patients who underwent ASCT at the Mayo Clinic between 1996 and 2001 were evaluated. A strong correlation between TILC and PA-ALC ( r = 0·67, P < 0·0001) was identified. Higher PA-ALC was observed in TILC ≥55 d compared with TILC <55 d [median: 7·0 vs. 3·8 × 109/l], P < 0·0001). TILC as a continuous variable was identified as a prognostic factor for overall survival (OS) [hazard ratio (HR) = 0·989, P < 0·01] and progression-free survival (PFS) (HR = 0·992, P < 0·0492). Median OS and PFS were longer in the TILC ≥55 d vs. TILC <55 d group (not reached vs. 21 months, P < 0·0008; 76 vs. 9 months, P < 0·0025, respectively). Multivariate analysis demonstrated TILC to be an independent prognostic indicator for OS and PFS. These findings suggest that the immune status of the host at the time of aphaeresis may predict survival after ASCT. [ABSTRACT FROM AUTHOR]

Background Scleromyxedema is a rare chronic fibromucinous disorder that can have devastating clinical manifestations, including sclerosis of the skin with progressive pharyngeal and upper airway involvement, resulting in high mortality due to respiratory complications. Herein we describe a novel therapeutic approach. Because autologous hematopoietic stem cell transplantation is effective in other plasma cell proliferative disorders, it may be effective in this setting. Observations We retrospectively evaluated 6 patients who were offered high-dose chemotherapy with stem cell rescue as treatment for scleromyxedema. One heavily pretreated patient was unable to mobilize stem cells. The remaining 5 patients mobilized stem cells and underwent successful transplantation. There was no treatment-related mortality. Hematologic responses were seen in 4 patients, including 2 complete remissions and 2 partial remissions, and all 4 had improvement in extracutaneous manifestations. All 4 patients subsequently had relapse of the monoclonal protein, and 3 developed skin relapses at 14, 37, and 45 months. Conclusions High-dose chemotherapy with stem cell rescue is feasible for patients with scleromyxedema and, although not curative, offers durable remission in most patients. This therapy should be considered before treatment with alkylating agents or other treatments that could adversely affect the ability to collect stem cells. [ABSTRACT FROM AUTHOR]

Absolute lymphocyte count (ALC) &geqslant; 500 cells/μl at day 15 after autologous stem cell transplantation (ASCT) is a powerful independent, prognostic indicator for survival in multiple hematological malignancies. A limitation in these studies was the selection of a single time point (day 15 post-ASCT) as the only discriminator of clinical outcome in relation to ALC recovery. We hypothesized there is a continuous and not discrete relationship between ALC recovery and clinical outcome post-ASCT in NHL. Therefore, we analyzed 274 consecutive patients who underwent ASCT for NHL between 1987 and 2001. The primary end point was to assess the impact of the kinetics of post-ASCT lymphocyte recovery &geqslant; 500 cells/μl (K-ALC) on overall survival (OS) and progression-free survival (PFS). K-ALC was a predictor of OS and PFS when the Cox proportional hazards model was used with K-ALC entered as a continuous variable ( p < 0.0001). Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that the K-ALC post-ASCT is associated with clinical outcome in NHL. [ABSTRACT FROM AUTHOR]

In the recent years, there have been multiple approvals by the Food and Drug Administration (FDA) for therapeutics for acute myeloid leukemia (AML). The role of maintenance therapy in AML has been rather unrealized mostly due to lack of efficacy and increased toxicity of classical chemotherapy agents. Many clinical trials have demonstrated a disease-free survival benefit for various therapeutics in the maintenance setting for patients with AML who are ineligible for stem cell transplant. Notably, oral hypomethylating agent therapy has recently shown an overall survival and disease-free survival benefit in the maintenance setting for AML. In this review, we summarize the relevant data on maintenance therapy with a specific focus on cytotoxic antimetabolite chemotherapeutics, hypomethylating agents, targeted agents, and immunotherapeutics. We discuss our approach to maintenance therapy in AML in 2021 and propose a measurable residual disease (MRD)-adapted, personalized approach based on the best available evidence. [ABSTRACT FROM AUTHOR]

Abstract: Historically, up to 30% of patients were unable to collect adequate numbers of peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (ASCT). Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has shown superior results in mobilizing peripheral blood (PB) CD34+ cells in comparison to G-CSF alone, but its high cost limits general use. We developed and evaluated risk-adapted algorithms for optimal utilization of plerixafor. In plerixafor-1, PBSC mobilization was commenced with G-CSF alone, and if PB CD34 on day 4 or day 5 was <10/μL, plerixafor was administered in the evening, and apheresis commenced the next day. In addition, if on any day, the daily yield was <0.5 × 106 CD34/kg, plerixafor was added. Subsequently, the algorithm was revised (plerixafor-2) with lower thresholds. If day-4 PB CD34 <10/μL for single or <20/μL for multiple transplantations, or day-1 yield was <1.5 × 106 CD34/kg, or any subsequent daily yield was <0.5 × 106 CD34/kg, plerixafor was added. Three time periods were analyzed for results and associated costs: January to December 2008 (baseline cohort; 319 mobilization attempts in 278 patients); February to November 2009 (plerixafor-1; 221 mobilization attempts in 216 patients); and December 2009 to June 2010 (plerixafor-2; 100 mobilization attempts in 98 patients). Plerixafor-2 shows a significant improvement in PB CD34 collection, increased number of patients reaching minimum and optimal goals, fewer days of apheresis, and fewer days of mobilization/collection, albeit at increased costs. In conclusion, although the earlier identification of ineffective PBSC mobilization and initiation of plerixafor (plerixafor-2) increases the per-patient costs of PBSC mobilization, failure rates, days of apheresis, and total days of mobilization/collection are lower. [Copyright &y& Elsevier]

Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5-year overall survival, 64%, 18%, and 50%, respectively; P = .0001). This scheme stratifies patients into 3 groups with similar nonrelapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applies to patients regardless of disease status (first or second complete remission), donor type (matched related or unrelated), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials. [ABSTRACT FROM AUTHOR]

Myelofibrosis is a myeloproliferative disorder incurable with conventional strategies. Several small series have reported long-term disease-free survival (DSF) after allogeneic hematopoietic cell transplantation (HCT). In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR). The median age was 47 years (range: 18-73 years). Donors were HLA identical siblings in 162 patients, unrelated individuals in 101 patients, and HLA nonidentical family members in 26 patients. Patients were treated with a variety of conditioning regimens and graft-versus-host disease (GVHD) prophylaxis regimens. Splenectomy was performed in 65 patients prior to transplantation. The 100-day treatment-related mortality was 18% for HLA identical sibling transplants, 35% for unrelated transplants, and 19% for transplants from alternative related donors. Corresponding 5-year overall survival (OS) rates were 37%, 30%, and 40%, respectively. DFS rates were 33%, 27%, and 22%, respectively. DFS for patients receiving reduced-intensity transplants was comparable: 39% for HLA identical sibling donors and 17% for unrelated donors at 3 years. In this large retrospective series, allogeneic transplantation for myelofibrosis resulted in long-term relapse-free survival (RFS) in about one-third of patients. [Copyright &y& Elsevier]

Introduction There have been considerable advances in the understanding of molecular markers in acute myeloid leukemia(AML). It is widely accepted that internal tandem duplication (ITD) in the juxta membrane domain of the fms-like tyrosine kinase-3 (FLT3) gene in patients with AML is associated with an increased risk of relapse and reduced overall survival. In several studies, alloSCT performed in first complete remission (CR) from matched-related donors (MRDs) has been shown to result in an improved survival. There is also evidence that alloSCT improves OS in high allelic ratio FLT3-ITD AML and in patients with low allelic ratio FLT3-ITD AML and wild-type nucleophosmin (NPM1) but not in mutated NPM1 with low FLT3 ITD ratio. We wanted to validate these findings in our own cohort. Methods We retrospectively reviewed 723 consecutive patients (>18 years) with newly diagnosed AML treated at Mayo clinic between January 2007 and July 2016. Patients with intermediate-risk cytogenetics and known NPM1 and FLT3 molecular genetics were included in the study (n =198). Patients who had M3 AML, who were lost to follow up and without molecular data were excluded. We analyzed outcomes based on therapy and molecular mutations. Results Baseline characteristics are listed in Table 1. As expected patients receiving alloSCT were younger and a higher proportion received high intensity induction therapy. The majority of patients were transplanted in CR 1 (72%, n=55), Table 2. Median time to transplant was 4.6 months (range 2-64 months). Median follow up for the entire cohort was 62 months. At last follow up 117 (59%) of patients have died. Median OS for the whole cohort was 27 months. OS was longer in patients receiving alloSCT (median OS 87 months vs 16 months for No SCT, p=0.0001)(Figure 1A). This survival advantage remained significant amongst patients achieving CR1 (Figure 1B). Molecular mutations predicted survival based on FLT3 and NMP1 status primarily amongst the non-transplant cohort (Figure 1C). Patients receiving SCT had a similar survival irrespective of molecular mutation profile(Figure 1D). Amongst the FLT3+ cohort, data on subtype and ITD allelic ratio were available in 47 patients (FLT3 ITD low allelic ratio (<0.5), n=13, FLT3 ITD high allelic ratio (≥0.5), n=26 and FLT3 TKD, n=8). Patients with a high allelic ratio FLT3 ITD mutation appeared to have the worst survival, although this did not meet statistical significance (median OS 69 months for FLT3 ITD low vs 21 months for FLT3 ITD high, p=0.16). Conclusion In our cohort, patients with intermediate risk AML achieving CR1 benefited from alloSCT. The poor prognostic impact of FLT3 mutations in this cohort may be abrogated by alloSCT. The FLT3 mutation burden (allelic ratio) may help further prognosticate this category of patients with intermediate risk AML. [ABSTRACT FROM AUTHOR]