Recently there is evidence that cytogenetics can refine prognostic information which can help make decision, especially about stem cell transplantation. The factors not included in the IPSS that affect survival are represented by red cell transfusion need,12 thrombocytopenia,13 and “unfavorable” karyotype. Regarding the latter, patients with unfavorable karyotype, which includes a complex karyotype or sole or 2 abnormalities such as +8, −7/7q−, i(17q), inv(3), −5/5q−, 12p−, or 11q23, had a median survival of 2 years compared with 5.2 years for those with a “favorable” karyotype, defined as no abnormality or any other apart from those included in the above category, the 5-year survival rates were 8% and 51%, respectively. The newly devised DIPSS Plus score11 incorporates these additional 3 variables for improved prognostic categorization. In a series of 793 patients, median survival times were 185, 78, 35, and 16 months for the low, intermediate-1, intermediate-2, and high-risk categories, respectively.

Based on its inclusion into a recommended prognostic tool DIPSS Plus, cytogenetics should not longer be considered investigational
.

Reilly JT, McMullin MF, Beer PA, Butt N, Conneally E, Duncombe A, Green AR, George Michaeel N, Gilleece MH, Hall GW, Knapper S, Mead A, Mesa RA, Sekhar M, Wilkins B, Harrison CN, Writing group: British Committee for Standards in Haematology. Guideline for the diagnosis and management of myelofibrosis. Br J Haematol. 2012 Aug;158(4):453-71. [123 references]
Jennifer Dunlap, MD, Katalin Kelemen, MD, PhD, Nicky Leeborg, MD, Rita Braziel, MD, Susan Olson, PhD, Richard Press, MD, PhD, James Huang, MD, Ken Gatter, JD, MD, Marc Loriaux, MD, PhD, Guang Fan, Association of JAK2 Mutation Status and Cytogenetic Abnormalities in Myeloproliferative Neoplasms and Myelodysplastic/Myeloproliferative Neoplasms Am J Clin Pathol. 2011;135(5):709-719.

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There are different kinds of PTLD.  Rituxan appears to have some role in the management of this condition. Several studies show that it reduces both the EBV titers and severity of PTLD. It can be given by itself of with low dose chemotherapy.

Some physicians advocte following the EBV titers and treating when they rise.  The strategy of following titers and giving prophylactic Rituxan has not been formally studied.  Most published studies have dealt with treating patients who already have PTLD.

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?Preengraftment — less than three weeks
?Immediate postengraftment — three weeks to three months
?Late postengraftment — more than three months

Unfortunately, infection is reported as the primary cause of death in 8% of autologous HCT patients and 17% to 20% of allogeneic HCT recipients. Many of these are CMV or varicelaa-zoster viral infections and may be prevented with drugs such as Acyclovir. High-dose intravenous acyclovir (500 mg/m2 3 times daily, from day < 5 until day > 30) followed by oral acyclovir (800 mg 4 times daily for 6 months) has been found to effectively reduce the incidence of CMV disease (52%–59% vs. 61%–75%) and increase overall patient survival. However, it is expensive and has side effects. The Infectious Diseases Society of America (IDSA) issued clinical practice guidelines for preventing opportunistic infections among HCT recipients, published in Biol Blood Marrow Transpant ; 2009 ; 15 : 1143 -1238. IDSA does not recommend open ended acyclovir prophylaxis. It says: “Acyclovir prophylaxis should be offered to all HSV-seropositive allogeneic recipients to prevent HSV reactivation during the early posttransplant
period (AI). The standard approach is to begin acyclovir prophylaxis at the start of the conditioning therapy and continue until engraftment occurs or until mucositis resolves, whichever is longer, or approximately 30 days after HCT.” It does appears from its discussion in this section that there may be a benefit for a longer patients who are seronegative positive for CMV or VZV but the guideline does not define how long and does not specifically recommend it.  NCCN does recommend a year of prophylaxis in CMV or VZV infected patients but otherwise only for 30 days.  The American Society of Bone Marrow Transplantation and CDC take the same position in an identical language to the ISDA.  

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The maximum age for allogeneic transplantation has been increasing as methods of transplantation and supportive care have advanced. Most centers are now considering unrelated donor transplantation for patients at around seventy year mark. Unfortunately this remains an ongoing source of controversy because the literature is contradictory and confusing, owing primarily to the lack of phase 3 studies, which, however, would be very difficult to do. This remains a matter for discussion between patient and physician and an individualized decision between them. The age of around 75 years is now being routinely approached in major centers.

Patients older then 30 years of age, do less well with allogeneic transplantation because they tolerate GVHD less well. There is some support for using fludarabine, a more immunosupressive drug, for such patients. Fludarabine based conditioning regimen may reduce the negative impact of age in older patients receiving an HLA-identical sibling stem cell transplant  Alemtuzumab is a new drug that has been studied and that may also decrease the risk of Graft versus Host Disease. A recent European retrospective review of the combination of Fludarabine, cyclophosphamide and antithymocyte globulin(FCA), with or without low dose total body irradiation, concluded that TBI might have a role. The overall survival was quite comparable for the two regimens, though significant differences were found following more detailed analysis of subgroups. FCA conditioning regimen seems suitable for very young patients with well-matched donors; in other settings the addition of TBI 2 Gy to the FCA regimen seems to offer a better chance of cure, in keeping with results of other recent studies

There is no comparative information for any specific conditioning regimen in young adults with Aplastic Anemia. FCA is as well supported as other alternatives. For that reason, since stem cell transplantation is well established for Aplastic Anemia and the conditioning regimens are a part of this established procedure, the FCA regimen should not be considered Experimental or Investigational and it is medically necessary. The evidence for TBI is weak for young patients and TBI is experimental and it is not medically necessary.

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Three randomized controlled trials (RCTs) that compared outcomes of hematopoietic sibling stem cell transplantation(SCT) to outcomes with conventional-dose chemotherapy in children with ALL did not demonstrate superiority of transplantation in all comers but did suggest that those at high risk for relapse or those in relapse who were able to obtain another remission, did better. The literature in general shows promising results for allogeneic SCT in patients in first complete response at high risk for recurrence, and in patients in second or greater remission. This conclusion is further supported by an evidence-based systematic review of the literature sponsored by the American Society for Blood and Marrow Transplantation (ASBMT)(Hahn et al). Outcomes following matched unrelated donor and umbilical cord blood transplants have improved significantly over the past decade and may offer outcome similar to that obtained with matched sibling donor transplants.

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While retrospective studies indicate that long-term steroid use increases the risk of PCP infection it is not known how these patients should be prophylaxed. The threshold for potential infection that warrants prophylaxis with its costs in side effects and expense is unknown, and the critical amount of immunosuppression necessary to increase risk for PCP is also unknown. Prophylaxis has been suggested for patients immunosuppressed owing to an underlying disease or immunosuppressive therapy. In some cancer centers, patients who receive corticosteroid therapy for longer than 4 weeks at a dose equivalent to 20 mg of prednisone per day are routinely are given PCP prophylaxis, as well as those in high-risk groups such as bone marrow transplant recipients and children with ALL.

In 2009, Kovacs and Masur summarized the first 100 years since identification of Pneumocystis. They concluded that in HIV-negative patients there is no reliable laboratory marker for risk of this infection, but that in these patients PCP is more likely to be an acute illness causing severe respiratory distress of rapid onset when compared with HIV-positive patients. That makes routine prophylaxis more reasonable. Their recommended approach is to use PCP prophylaxis in patients receiving at least 20 mg of prednisone per day for at least 1 month. They also note that steroid therapy can accelerate symptomatic and physiologic improvement and improve survival in patients with moderate or severe PCP. Since steroids are in themselves immunosupressive, management of corticosteroids in PCP-infected patients is quite complex.

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