Chapter
Non-classical HLA alleles and matching techniques: Impact on outcomes
Chapter 3 Risk-benefit assessment in allogeneic hematopoietic transplant: Factors, scores, and models
What are the factors to consider prior to HCT?
Models used for risk-benefit measurement
Models estimating incidences of NRM
Models estimating relapse risk
Models estimating all-cause mortality
How to evaluate a patient for fitness for HCT
Guidelines on pretransplantation data gathering
Summary and practice points for eligibility for HCT
Chapter 4 Donor and recipient pre‐transplant evaluation
Donor infectious evaluation
Special consideration for potentially unsafe products
Donor non-infectious evaluation
Instrumental investigations
Special consideration for female donors of child‐bearing age group
Recipient infectious evaluation
Recipient non-infectious evaluation
Assessment of disease type and status
Assessment of functional status and comorbidities
Assessment of psychosocial, financial, and caregiver issues
Chapter 5 Autologous and allogeneic progenitor cell mobilization
What if CD34+ cell mobilization fails?
Some practical aspects of autologous CD34+ cell mobilization
Allogeneic CD34+ cell mobilization
What is the best CD34+ cell mobilization regimen for allogeneic healthy volunteer donors?
What is the optimal PB CD34+ cell dose for allogeneic hematopoietic cell transplantation?
Chapter 6 Hematopoietic stem and progenitor cell collection by apheresis: Techniques and tricks
Collection techniques and devices used
Technical/clinical aspects of HPC (A) collections
Large volume leukapheresis (LVL)
Anticoagulation during HPC (A) collection
Special considerations for pediatric HPC donors/patients
Efficiency of CD34+ cell collection
Prediction by pre-collection CD34+ count and its impact on HPC (A) collection
Adverse effects associated with HPC (A) collections
HPC (A) collection quality indicators
Chapter 7 Hematopoietic cell processing: From procurement to infusion
Processing of autologous products
Optimizing cell concentrations during processing
Cryopreservation: Storing HPC products for use at a later date
Graft infusion: Wash or not to wash?
DMSO associated adverse effects and prevention
Controlled rate versus uncontrolled rate
Vapor phase LN2 versus liquid phase LN2
Processing allogeneic products
HPC, apheresis allogeneic products
HPC, marrow allogeneic products
HPC, cord blood allogeneic products
Regulation of handling UCB
Potency of the HPC product
Infectious disease testing
Chapter 8 Graft manipulation: T-cell depletion and beyond
Acute and chronic GvHD: Scope of the problem
Concepts and methods of TCD
Impact of T-cell depletion on engraftment
Impact of TCD on GvHD: Comparisons with conventional allo-HCT
Impact of TCD on malignant relapse
Impact of TCD on immune recovery
Optimal patient selection for TCD allografts
Future directions: Other approaches to TCD
Chapter 9 Graft-versus-host disease prophylaxis
Pharmacological prophylaxis for GvHD
Combinations using calcineurin inhibitors
1-Cyclosporine plus methotrexate
2-Tacrolimus (FK 506) plus methotrexte
3-Calcineurin inhibitors plus mycophenolate mofetil (MMF)
Pharmacologic T-cell depletion
1-Antithymocyte globulin (ATG)
2-Alemtuzumab (campath-1H)
Investigational therapies
Use of post-transplant cyclophosphamide (ptCy) to prevent GvHD
Chapter 10 Acute lymphoblastic leukemia
ALL risk stratification – an evolving paradigm
Has MRD refined the risk-directed strategy for adult ALL?
Philadelphia chromosome-negative (Ph−) ALL
Philadelphia chromosome-positive (Ph+) ALL
Optimal post-remission therapy for adults with ALL in CR1
Data with myeloablative conditioning regimen and HLA-MSD and HLA-matched Urelated Donor
Philadelphia chromosome-positive (Ph+) ALL
Transplant from an alternative donor using MAC/ regimen in CR1
HLA-Haploidentical transplants
Emerging role for RIC regimens in ALL
Does intensity of conditioning regimen matters in ALL?
How to evaluate MRD after allo‐HCT and what action to take?
Is there evidence to merit chimerism monitoring in ALL?
Does DLI post-allo-HCT for ALL work?
Post-allo-HCT TKI for Ph+ ALL
Chapter 11 Acute myeloid leukemia
Transplant versus chemotherapy for post-remission therapy
Who should receive allogeneic transplant?
Is allogeneic transplant needed?
Timing of allogeneic transplant
Transplant in relapsed or refractory AML
Measurable residual disease (MRD)
Reduced-intensity conditioning (RIC)
Post-transplant strategies to prevent relapse
Chapter 12 Myelodysplastic syndromes
Disease classification, risk stratification, and allo-HCT
Indications for transplantation
Optimal conditioning regimen: Do we know?
Graft from peripheral blood or marrow?
Beyond HLA-matched grafts: Is it reasonable approach?
Role of therapy and disease burden prior to allo-HCT
Treatment and prevention of post- HCT relapse
Limitations and future prospects
Chapter 13 Chronic myelogenous leukemia
The past informs the present: lessons from the BMT era
Does disease phase matter?
Time before transplant and outcome
Does the preparative regimen matter?
Does donor type affect outcome?
Peripheral blood or bone marrow?
Is there an established role for T-cell depletion?
Up-front allogeneic HCT for first chronic phase: Why or why not?
OK, who should get a transplant?
Management of post‐transplant relapse
Monitoring disease post-transplant: Can relapse be prevented?
Is there a role for autologous transplantation?
Chapter 14 Philadelphia chromosome negative myeloproliferative neoplasms
Prospective and retrospective studies of allo-HCT
What is the optimal conditioning regimen for PMF?
Role of molecular markers
Bone marrow fibrosis regression: Is it possible after allo-HCT?
Selecting the optimal donor
Disease-specific risk scores and optimal timing of allo-HCT
Role of spleen size and splenectomy in anticipation for allo-CT
Role of JAK inhibition prior to allo-HCT
The problem of graft failure and poor graft function
Treatment and prevention of relapse after allo-HCT
Conflict of Interest Statements
Chapter 15 Chronic lymphocytic leukemia
Allogeneic transplant in CLL: Is this required in an indolent disease?
What are prospectively validated negative predictors for response and survival?
“High-risk CLL”: What does this imply?
What is the evidence for the efficacy of allo-HCT in CLL?
What are adverse events and risks associated with allo-HCT in CLL?
What determines the success of allo‐HCT in CLL?
Should MRD kinetics and GvL activity be monitored after allo-HCT?
What is the outcome of patients who relapse after allo-HCT?
Is there a role for autologous hematopoietic cell transplantation in CLL?
Do alternative immunochemotherapy-based treatment options for patients with p53 abnormalities exist?
Are novel treatments changing the standard of care in CLL?
Are novel agents active in high-risk CLL patients?
Are there additional limitations to novel agents?
What are the limitations of CAR T-cells?
Is allo-HCT still a valid treatment option in the era of novel treatments?
Which patients should be offered allo-HCT in the era of novel agents?
Chapter 16 Hodgkin Lymphoma
Auto-HCT for Hodgkin Lymphoma: The HD 01 trial
Prognostic factors for long‐term outcomes after autologous- HCT
First-line salvage chemotherapy before auto-HCT
Salvage therapy and effect on graft mobilization
Positive PET-CT and role of second-line salvage for patients eligible for high-dose therapy: The role of brentuximab vedotin
Can we improve the results of auto‐HCT?
Tandem transplant versus consolidation therapy after auto-HCT
Hodgkin Lymphoma relapsing after first auto-HCT: Allogeneic HCT or second auto-HCT?
Allo-HCT for Hodgkin Lymphoma
Allogeneic transplantation in patients failing after an auto-HCT
Moving allo-HCT to earlier phase of the disease
Do we have any evidence of a GvHL effect?
Increasing the pool of donors for HL patients having an allo-HCT: Beyond HLA-MSD and HLA-MUD
Cord blood transplants in HL
HLA-haploidentical transplants in HL
Chapter 17 Indolent lymphomas
HCT in first remission: Auto-HCT versus allo-HCT
HCT for relapsed FL: Auto-HCT versus MA- allo-HCT
HCT for relapsed FL: Auto-HCT versus RIC allo-HCT
HCT for relapsed FL: Chemoimmunotherapy/allo-HCT versus tandem auto/allo-HCT
Post auto-HCT maintenance therapy in FL: Where are we now?
Transformed FL: Is there a role for HCT?
Upfront auto-HCT in MCL: Transplant in first remission
Relapsed/refractory MCL: Auto-HCT versus allo-HCT
Waldenström macroglobulinemia
Small lymphocytic lymphomas
Auto-HCT and second malignancies
Future efforts directed on improving the role of HCT in indolent lymphomas
Chapter 18 Diffuse large B-cell lymphoma
Risk stratification – The Revised International Prognostic Index: Is it still relevant?
What is the consensus for auto-HCT in R/R DLBCL?
Should rituximab be part of the first salvage regimen?
Does duration of first remission and exposure to rituximab as part of initial therapy influence subsequent outcome?
Is there one best salvage regimen for patients with R/R DLBCL?
Incorporation of Ofatumumab in R/R DLBCL
Does cell of origin of de novo DLBCL and c-MYC gene rearrangement influence the outcomes with auto-HCT?
Frontline autologous-HCT: Yes or no?
What is the ideal conditioning regimen for auto-HCT?
Rituximab as post-transplant maintenance therapy: Yes or no?
Post-auto-HCT maintenance therapy: Novel approaches are underway
Outcomes of auto-HCT in patients who failed the first salvage regimen
Allogeneic-HCT for DLBCL: Eligibility and timing
What are the results of allo-HCT in DLBCL?
GvL effect: Does it apply in DLBCL?
Conditioning regimen for allogeneic HCT: What is the correct intensity?
Chapter 19 Mantle cell lymphoma
Front line therapy in MCL
Is the addition of rituximab and/or cytarabine to frontline therapy beneficial?
Is intensification of induction therapy beneficial?
Elderly or “unfit” patients (unfit to receive auto-HCT)
Consolidation/maintenance treatment after frontline therapy
For transplant eligible patients (young “fit” patients)
For transplant-ineligible patients (elderly patients)
Is maintenance therapy a suitable alternative for auto-HCT in transplant eligible patients?
What is the role of radioimmunotherapy consolidation in MCL?
Conditioning regimen for auto-HCT in MCL – Does it matter?
Post–auto-HCT maintenance therapy in MCL – are we there yet?
Relapsed/refractory MCL – what are the options?
Relapsed/refractory patients eligible for transplant
Relapsed/refractory patients ineligible for transplant
Is a risk-adapted approach feasible?
Novel agents – what are the challenges faced?
Minimal residual disease analysis – is it ready for prime time?
Chapter 20 T-cell lymphoma
What are the subtypes of PTCL and what are their geographic distributions?
What is the standard evaluation for a patient suspected to have PTCL?
Is there a standard upfront regimen for T-NHLs (excluding CTCL/MF)?
What agents are available for relapsed or refractory disease?
Data for HCT (auto and allo) in PTCL
Role of frontline auto‐HCT
Role of frontline allo‐HCT
Chapter 21 Primary CNS lymphoma
Epidemiology, pathology, and clinical presentation
Auto-HCT in the setting of recurrent or refractory PCNSL: Does it work?
Auto-HCT as front line treatment: Is there a straightforward answer?
Comparison between types of consolidation: Non-myeloablative chemotherapy versus auto-HCT
Eligibility criteria for auto-HCT
Is HIV associated Primary CNS lymphoma a contraindication for auto-HCT?
What is the best induction regimen before auto-HCT?
Is achievement of complete remission necessary before proceeding to consolidation with auto-HCT?
Conditioning regimen: Is there a standard?
What is the role of WBRT?
What is the role of intrathecal chemotherapy?
Chapter 22 Autologous hematopoietic transplant in multiple myeloma
What is the role of induction therapy prior to auto-HCT?
Addition of third agent with a backbone of VD: Is that a standard?
Is auto-HCT reasonable after excellent responses from three-drug combination?
What is the role of chemotherapy induced mobilization?
The addition of bortezomib appears to add benefit
Tandem auto-HCT as consolidation
Combination of novel agents in consolidation after auto-HCT
Choice of maintenance therapy
Age as a factor for auto-HCT: What is the upper limit?
Chapter 23 Allogeneic hematopoietic transplant in multiple myeloma
Allogeneic transplant in MM: How did we get here?
What are the randomized data regarding the role of upfront allo-HCT in MM?
Why is there discrepancy between randomized study results?
Graft-versus-MM effect: Does it exist?
Selection of patients for allo-HCT – Defining risk
Deciding on allo-HCT for the high-risk MM patient in practice
Does allo-HCT benefit high-risk patients or after relapse?
Timing of allo-HCT: Upfront or at early relapse or late relapse?
Plasma cell leukemia and allo-HCT
Planned post-transplant maintenance or cell therapy after allo-HCT
Minimal residual disease (MRD) evaluation in allo-HCT
Relapse after allo-HCT in MM
Emerging immunotherapy approaches
Chapter 24 Light-chain amyloidosis
History and current data of transplantation for AL amyloidosis
Do patients need induction chemotherapy prior to auto-HCT?
Mobilization and collection of CD34+ cells
Conditioning chemotherapy
Supportive care: Important aspects in candidates for auto-HCT
Post-transplant consolidation
Role of allogeneic transplant in AL amyloidosis
Role of solid organ transplant in AL amyloidosis
Non-transplant chemotherapy options
Current status and future directions
Chapter 25 Autoimmune disorders
Strategies employing HCT in AID
Transplant activity, indications, and outcomes
Autologous hematopoietic cell mobilization and collection
Conditioning regimens for autologous HCT
Early and late complications of HCT and supportive care during HCT
Chapter 26 Testicular cancer
AHCT for GCT: What are the outcomes and which patient should be considered?
So why does widespread use of HDCT/AHCT for relapsed GCTs continue?
HDCT/AHCT: How is it done?
Efficacy and Toxicity: How can we maximize efficacy while limiting the toxicity?
Chapter 27 Sickle cell disease
The importance of tracking the natural history of sickle cell disease (SCD)
The changing indications for allo-HCT in SCD
Traditional indications for allo-HCT
Additional indications that signal severity of SCD but can add to allo-HCT toxicities
Relative contraindications to allo-HCT in SCD-will increase allo-HCT related morbidity/mortality
Donor availability for allo-HCT
Transplant trials in SCD – Preparative regimens
Toxicities and supportive care – Not to be forgotten after HCT
SCD related risks/precautions
Chapter 28 Hematopoietic cell transplant in thalassemia
Expected results of transplantation for thalassemia
Indications for allo-HCT in thalassemia
Risk factors for outcomes with allo-HCT in thalassemia
Pesaro results (1980s to early 1990s)
Lessons from the Pesaro experience
Current results with allo-HCT in thalassemia
Adult patients (≥18 years)
HLA-matched sibling cord blood transplant
Beyond HLA-MSD and HLA-matched sibling CB units
Non-HLA-identical family donor
HLA-matched unrelated donor (MUD)
Pretransplantation assessment
Should a spleenectomy be performed?
What about cardiac status?
Outcome of graft source other than bone marrow in an HLA-MSD setting
Myeloablative condition (MAC) regimen is preferred
GvHD prophylaxis: Regimen and duration
Follow-up evaluation post-transplant
Interpretation of chimerism and its implications
Other important management aspects after allo-HCT
Iron overload: Still an issue
Chronic hepatitis and liver fibrosis
Long-term health-related quality of life
Chapter 29 Fanconi anemia
Historical perspective of allo-HCT in FA
Allo-HCT for FA patients: Appropriate candidate and timing
What is the consensus on conditioning regimen and GvHD prophylaxis for allo-HCT in patients with FA?
Hematologic malignancies in FA patients: Should chemotherapy be performed before allo-HCT?
Long-term follow-up after allo-HCT in FA patients: Challenges?
Follow-up before and after allo-HCT
Chapter 30 Immunodeficiency disorders
Timing – When do the benefits outweigh the risks?
What are key differences between allo-HCT for PID and allo-HCT for malignancy?
Donor Selection – What to do when there is no HLA-matched sibling
Chimerism and cure: How much is enough?
Chapter 31 Inherited metabolic disorders
Allogeneic-HCT in IEM: What is the rationale and how did we get here?
Which diseases to transplant?
Are outcomes of HCT in IEM satisfying and how can we further optimize the outcomes?
How to transplant a patient with an IEM?
Are there alternative treatment options for patients with an IEM?
Adjuvant therapies to allo-HCT
Chapter 32 Aplastic anemia and paroxysmal nocturnal hemoglobinuria
Diagnostic approach: Differentiating between toxic damage and inherited marrow failure
Treatment options for SAA
Best treatment option for younger patients: HLA-matched sibling allo-HCT
When patients fail or relapse after IST
Is it appropriate to use a HLA-mismatched unrelated donor (MMUD)?
What about patients who fail multiple attempts at immune suppression and don’t have HLA-MUD: Do they have transplantation options?
A word about paroxysmal nocturnal hemoglobinuria
How should SAA patients be followed after therapy?
SAA Patients treated with IST
SAA patients treated with allo‐HCT
Chapter 33 HIV infection and transplantation
Evaluation of a suspected patient with HIV lymphoma
What are the data with AHCT in HIV associated lymphoma?
Discrepancy between studies
Which patients are suitable candidates for AHCT?
Allogeneic transplantation in HIV
Data for allo–HCT in HIV infected individuals: Where do we stand?
Allo-HCT in hematologic malignancies: Moving forward
Allo-HCT for HIV infection
Gene therapy for HIV infection
Chapter 34 Engraftment and graft failure: Assessment and practical considerations
Methods for chimerism analysis
How to select suitable STR markers for chimerism analysis
Which cells are used for chimerism/engraftment analysis?
Chimerism and reduced-intensity conditioning
Detection of imminent leukemia relapse post-transplant by chimerism analysis
Major risk factors for graft failure
Treatment of graft failure
Chapter 35 Immune reconstitution and tolerance
When and how are the different immune components reconstituted?
Early post-transplantation period relies on homeostatic peripheral expansion
Thymopoiesis recovery is delayed after HCT: Why and how do I monitor its recovery?
How does tolerance develop after HCT?
What are the different strategies to enhance immune reconstitution following transplantation?
Chapter 36 Donor lymphocyte infusion
What is the rationale for donor lymphocyte infusions (DLIs)?
What factors should be considered in deciding to proceed with a DLI?
How are donor lymphocytes collected?
How is a DLI administered?
What is an optimal dose of CD3+ cells?
Should the DLI be preceded by disease specific therapy?
Is there a role for recipient lymphodepletion prior to DLI?
Should the recipient be on immunosuppression at the time of DLI?
How long does it take for a DLI to work?
What are the side effects of DLI?
Limitations of data regarding DLI
What are some of the disease specific considerations for DLIs?
Low-grade NHL, CLL, and MCL
Chapter 37 Diagnosis and treatment of acute graft-versus-host disease
Pathophysiology and risk factors of aGvHD
Do we completely understand the pathophysiology of aGvHD?
Some important risk factors associated with aGvHD
Diagnosis and clinical manifestations of aGvHD
What are the chances of getting aGvHD and what is the usual timing?
Clinical manifestations of gastrointestinal GvHD
Clinical manifestations of cutaneous GvHD
Clinical manifestations of hepatic GvHD
What is the differential diagnosis of aGvHD?
Is biopsy necessary in diagnosing aGvHD?
Is radiographic imaging needed in diagnosing aGvHD?
Grading aGvHD – Is one classification better than the other?
Who does not need systemic therapy for aGvHD?
How should corticosteroids be given for initial therapy of aGvHD?
Should another drug be added to corticosteroids for initial therapy of aGvHD?
What should be used when first‐line therapy for aGvHD fails?
What supportive care measures can be used for aGvHD?
What is the prognosis of patients with aGvHD?
Summary of diagnosis and treatment of aGvHD
Chapter 38 Diagnosis and treatment of chronic graft-versus-host disease
Definition and clinical manifestations
GvHD global severity score
How effective is aGvHD prophylaxis for cGvHD?
How about rituximab for prevention of cGvHD?
T-cell depletion for cGvHD
cGvHD in cord blood transplants and HLA-haploidentical transplants with post cyclophosphamide
What is the best initial therapy for cGvHD?
Steroids in cGvHD: Dose and schedule?
What are the second-line treatment options?
Extracorporeal photopheresis
Mycophenolate mofetil (MMF)
Is there a role for cellular therapy in prevention or treatment of cGvHD?
Treg-cells: Do they really work in cGvHD?
Does treatment of cGvHD increase relapse-related mortality?
Chapter 39 Prevention and treatment of infection
Prevention of bacterial infections
Antibacterial prophylaxis: Challenge in the era of multi-resistance
Prevention of bacterial infections after PMN engraftment
Prevention of fungal infections
How to plan an antifungal prophylaxis strategy
Secondary antifungal prophylaxis
Prophylaxis of Pneumocystis pneumonia
Prevention of viral infections in HCT patients
Prophylaxis of herpesvirus diseases
Prophylaxis of HBV reactivation
Treatment of infections in HCT recipients
Neutropenic fever in HCT recipients
Fever in non‐neutropenic HCT recipients
Chapter 40 Early non-infectious complications after hematopoietic cell transplantation
How can we grade regimen‐related toxicities?
Gastrointestinal and hepatic complications
Nausea, vomiting, and anorexia
Esophagitis and gastritis
Proton-pump inhibitors (PPIs)
H2 antagonists (ranitidine, famotidine, nizatidine, cimetidine)
Sinusoidal obstruction syndrome (SOS)
Diffused alveolar hemorrhage
Idiopathic pneumonia syndrome
Kidney and bladder complications
Common etiologies and managements
Chapter 41 Post-transplant lymphoproliferative disorders
Presentation and diagnosis
Removal/reduction of immune suppression
Monoclonal antibody against CD 20 receptor on B-cells
EBV-specific T-cell therapy
Chapter 42 Survivorship issues after transplantation
What are the late complications after HCT?
Secondary solid malignancies
Which type of secondary solid malignancies occur after HCT?
What are the risk factors for secondary solid malignancies?
Pre-transplant risk factors
Transplant-associated risk factors
Post-transplant risk factors
Screening for secondary malignancies: What are the recommendations?
Late infectious complications
What are the vaccination recommendations for HCT recipients?
What are the vaccination recommendations for close contacts?
New considerations: Pre-transplant vaccines
Models for providing long-term care
Clinical Manual of Blood and Bone Marrow Transplantation
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